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Sample records for chinese healthy volunteers

  1. Pharmacokinetics of ambroxol and clenbuterol tablets in healthy Chinese volunteers

    PubMed Central

    Yang, Yong-Ge; Song, Li-Xue; Jiang, Nan; Xu, Xue-Ting; Di, Xiao-Hui; Zhang, Mei

    2015-01-01

    Objective: To investigate the pharmacokinetics of Ambroxol and Clenbuterol Tablets in Chinese healthy volunteers after a single or multiple dosages oral administration. Methods: A total of 9 healthy adult subjects were given Ambroxol and Clenbuterol Tablets in a single dosage or multiple dosages respectively. LC/MS/MS were used for the determination of Ambroxol and Clenbuterol of in plasma. The important pharmacokinetic parameters were calculated by DAS 2.0 software (compartment model). Results: Single and multiple dosage groups of Ambroxol and Clenbuterol were all fitted two-compartment model. The pharmacokinetics fitted first order kinetics process. No difference in pharmacokinetics of Ambroxol in single and multiple dosage groups volunteers was observed, Which showed no marked changes, suggesting that multiple dosing did not influence the velocity of drug metabolism. Moreover, parameters of Clenbuterol had significant difference between the single and multiple dosage groups (P<0.05), showing there was accumulation in the body. 9 subjects had completed single or multiple dosages oral administration test, with no adverse drug reactions appeared during the test. Conclusion: There was no obvious accumulation of Ambroxol after repeated dosing. But obvious accumulation of Clenbuterol was noted in multiple-dose administration. The established method is sensitive, accurate, reliable and specific, and it can meet the requirement of clinical pharmacokinetic trial. PMID:26770490

  2. Effect of tamsulosin on the pharmacokinetics of dutasteride in Chinese male healthy volunteers.

    PubMed

    Li, Huafang; Yang, Jiansong; Zhao, Hongxin; Fossler, Michael J; Wang, Chunrong

    2015-11-01

    The purpose of this study was to evaluate the effect of tamsulosin (0.2 mg) on the pharmacokinetics of dutasteride (0.5 mg) in a group of healthy Chinese male volunteers. This was an open-label, single-sequence, 3-period, drug-drug interaction phase 1 study. Twenty-four healthy Chinese male volunteers were enrolled and administered a single dose of 0.5 mg dutasteride and, following a 28- to 30-day washout period, 0.2 mg tamsulosin once daily for 7 days. On day 5, subjects received 0.2 mg tamsulosin coadministered with 0.5 mg dutasteride. Serum dutasteride and tamsulosin concentrations were monitored. In the presence or absence of tamsulosin, there were no apparent changes in dutasteride AUC and Cmax . Adverse events reported were mild to moderate in intensity and resolved by the end of the study. In healthy Chinese male volunteers, tamsulosin 0.2 mg at steady state had no apparent effect on dutasteride pharmacokinetics. Dutasteride and tamsulosin when administered alone or in combination were well tolerated.

  3. Effect of tamsulosin on the pharmacokinetics of dutasteride in Chinese male healthy volunteers.

    PubMed

    Li, Huafang; Yang, Jiansong; Zhao, Hongxin; Fossler, Michael J; Wang, Chunrong

    2015-11-01

    The purpose of this study was to evaluate the effect of tamsulosin (0.2 mg) on the pharmacokinetics of dutasteride (0.5 mg) in a group of healthy Chinese male volunteers. This was an open-label, single-sequence, 3-period, drug-drug interaction phase 1 study. Twenty-four healthy Chinese male volunteers were enrolled and administered a single dose of 0.5 mg dutasteride and, following a 28- to 30-day washout period, 0.2 mg tamsulosin once daily for 7 days. On day 5, subjects received 0.2 mg tamsulosin coadministered with 0.5 mg dutasteride. Serum dutasteride and tamsulosin concentrations were monitored. In the presence or absence of tamsulosin, there were no apparent changes in dutasteride AUC and Cmax . Adverse events reported were mild to moderate in intensity and resolved by the end of the study. In healthy Chinese male volunteers, tamsulosin 0.2 mg at steady state had no apparent effect on dutasteride pharmacokinetics. Dutasteride and tamsulosin when administered alone or in combination were well tolerated. PMID:27137714

  4. [The enantioselective pharmacokinetic study of desvenlafaxine sustained release tablet in Chinese healthy male volunteers after oral administration].

    PubMed

    Chen, Yin-xia; Du, Jiang-bo; Zhang, Yi-fan; Chen, Xiao-yan; Zhong, Da-fang

    2015-04-01

    A chiral LC-MS/MS method for the simultaneous analysis of desvenlafaxine (DVS) enantiomers in human plasma was developed and applied to a pharmacokinetic study on 12 Chinese healthy volunteers. d6-Desvenlafaxine was used as internal standard (IS). Chromatographic separation was performed on the Astec Chirobiotic V chiral column (150 mm x 4.6 mm, 5 μm). The assay was linear over the concentration range of 0.500-150 ng x mL(-1) for both enantiomers (r2 > 0.99). The method was successfully applied to a stereoselective pharmacokinetic study of 100 mg desvenlafaxine sustained release tablets on 12 Chinese healthy volunteers under fasting conditions. The results showed that the pharmacokinetic parameters were similar to both enantiomers in Chinese healthy volunteers. The AUC(0-t), and C(max) of the two enantiomers were about 1.5 times higher than those of blacks and whites reported in the literature.

  5. Effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in healthy Chinese volunteers

    PubMed Central

    Zhang, Yi-fan; Dai, Xiao-jian; Yang, Yong; Chen, Xiao-yan; Wang, Ting; Tang, Yun-biao; Tsai, Cheng-yuan; Chang, Li-wen; Chang, Yu-ting; Zhong, Da-fang

    2016-01-01

    Purpose To investigate the effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in humans. Methods Two independent, open-label, randomized, crossover studies were conducted in 24 (12 per study) healthy Chinese volunteers. In Study 1, each volunteer received a single oral dose of 500 mg of nemonoxacin alone or with 1.5 g of probenecid divided into three doses within 25 hours. In Study 2, each volunteer received a single oral dose of 500 mg of nemonoxacin alone or with multiple doses of cimetidine (400 mg thrice daily for 7 days). The plasma and urine nemonoxacin concentrations were determined using validated liquid chromatography–tandem mass spectrometry methods. Results Coadministration of nemonoxacin with probenecid reduced the renal clearance (CLr) of nemonoxacin by 22.6%, and increased the area under the plasma concentration–time curve from time 0 to infinity (AUC0−∞) by 26.2%. Coadministration of nemonoxacin with cimetidine reduced the CLr of nemonoxacin by 13.3% and increased AUC0−∞ by 9.4%. Coadministration of nemonoxacin with probenecid or cimetidine did not significantly affect the maximum concentration of nemonoxacin or the percentage of the administered dose recovered in the urine. Conclusion Although probenecid reduced the CLr and increased the plasma exposure of nemonoxacin, these effects are unlikely to be clinically meaningful at therapeutic doses. Cimetidine had weaker, clinically meaningless effects on the pharmacokinetics of nemonoxacin. PMID:26855561

  6. Gender differences in pharmacokinetics of a combination tablet of niacin extended-release/simvastatin in healthy Chinese volunteers.

    PubMed

    Wang, Xiao-lin; Liu, Man; Yang, Man; Zhang, Ya-nan; Zhang, Dan; Zhang, Li-na; Han, Jing; Liu, Hui-chen

    2014-12-01

    The gender differences in pharmacokinetics of a combination tablet of niacin extended-release/simvastatin were evaluated in healthy Chinese volunteers. Thirty-six healthy male and female volunteers were enrolled in the study receiving a single oral dose of niacin extended-release/simvastatin 1,000/20 mg. The results indicated that the systemic exposure of simvastatin hydroxy acid and the total urine excretion of niacin were significantly higher for females compared with those for males, and the T max of niacin in plasma was significantly shorter for males than that for females. There were no significant differences in the systemic exposure of simvastatin, niacin, and NUA in plasma between males and females.

  7. Bioequivalence assessment of two formulations of spironolactone in Chinese healthy male volunteers.

    PubMed

    Xu, Feng-Guo; Zhang, Zun-Jian; Dong, Hai-Juan; Tian, Yuan; Liu, Ying; Chen, Yun

    2008-01-01

    The bioavailability of a new spironolactone ((7alpha,17alpha)-7-(acetylthio)-17-hydroxy-3-oxopregn-4-ene-21-carboxylic acid gamma-lactone, CAS 52-01-7) formulation (test) was compared with a commercially available original formulation (reference) of the drug in 20 Chinese healthy male volunteers, aged between 21 and 27. The trial was designed as an open, randomized, single blind two-sequence, two-period crossover study. Under fasting conditions, each subject received a single oral dose of 100 mg spironolactone as a test or reference formulation with a 7-day washout period between the two formulations. The plasma concentrations of spironolactone and its active metabolite canrenone (CAS 976-71-6) were analyzed by a sensitive liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS) method. The pharmacokinetic parameters included AUC(0.t), AUC(0-infinity), C(max), t1/2, and T(max). Values of AUC(0-t) demonstrate nearly identical bioavailability of spironolactone from the examined formulations. The AUC(0.12) of spironolactone was 148.35 +/- 39.5 and 144.39 +/- 53.02 ng x h/ml for the test and reference formulation, respectively. The AUC(0-60) of the metabolite canrenone was 1873.36 +/- 318.10 and 1911.28 +/- 355.60 ng h/ml for test and reference formulation, respectively. The maximum plasma concentration (C(max)) of spironolactone was 48.34 +/- 21.16 ng/ml for the test and 47.40 +/- 23.40 ng/ml for the reference product and the C(max) of the metabolite was 122.90 +/- 27.70 and 123.35 +/- 27.29 ng/ml for the test and reference product, respectively. No statistical differences were observed for C(max) and the area under the plasma concentration-time curve for both spironolactone and its active metabolite canrenone. 90% confidence limits calculated for C(max) and AUC from zero to infinity (AUC(0-infinity)) of spironolactone and its metabolite were included in the bioequivalence range (80%-125% for AUC). This study shows that the test

  8. Pharmacokinetics of a multicomponent herbal preparation in healthy Chinese and African volunteers

    PubMed Central

    Alolga, Raphael N.; Fan, Yong; Zhang, Gang; Li, Jin; Zhao, Yi-Jing; Lelu Kakila, Jimmy; Chen, Yan; Li, Ping; Qi, Lian-Wen

    2015-01-01

    K-601 is an herbal formulation for influenza consisting of Lonicera japonica, Isatis indigotica, Rheum palmatum, Phellodendron chinense, and Scutellaria baicalensis. In this work, we characterized the chemical constituents in K-601, identified the absorbed compounds and determined their pharmacokinetics in 6 Chinese and African volunteers by liquid chromatography with time-of-flight mass spectrometry. Similarity evaluation for chromatographic fingerprint of nine different batches showed values above 0.983. Totally, 50 components were identified in K-601. Then, 15 major prototype compounds and 17 metabolites were identified in human plasma. Major metabolic pathways included glucuronidation, sulfation, methylation, demethylation, and reduction. The pharmacokinetics of the most abundant prototype compounds, berberine, jatrorrhizine, palmatine and magnoflorine were determined. Significant pharmacokinetic differences were observed between the African and Chinese subjects. The AUCs of the African is about 4–10 fold higher than that of the Chinese for the three benzylisoquinoline alkaloids. Magnoflorine, an aporphine alkaloid, was absorbed better in the Chinese than in the African. The biotransformation of K-601 by human intestinal microflora was also investigated. The major reactions included hydroxylation, methylation, demethylation, acetylation and reduction. Glucuronidation and sulfation were not observed with fecal flora. These results may be important and useful in linking data from pharmacological assays and clinical effects. PMID:26268432

  9. Pharmacokinetics of a multicomponent herbal preparation in healthy Chinese and African volunteers.

    PubMed

    Alolga, Raphael N; Fan, Yong; Zhang, Gang; Li, Jin; Zhao, Yi-Jing; Lelu Kakila, Jimmy; Chen, Yan; Li, Ping; Qi, Lian-Wen

    2015-01-01

    K-601 is an herbal formulation for influenza consisting of Lonicera japonica, Isatis indigotica, Rheum palmatum, Phellodendron chinense, and Scutellaria baicalensis. In this work, we characterized the chemical constituents in K-601, identified the absorbed compounds and determined their pharmacokinetics in 6 Chinese and African volunteers by liquid chromatography with time-of-flight mass spectrometry. Similarity evaluation for chromatographic fingerprint of nine different batches showed values above 0.983. Totally, 50 components were identified in K-601. Then, 15 major prototype compounds and 17 metabolites were identified in human plasma. Major metabolic pathways included glucuronidation, sulfation, methylation, demethylation, and reduction. The pharmacokinetics of the most abundant prototype compounds, berberine, jatrorrhizine, palmatine and magnoflorine were determined. Significant pharmacokinetic differences were observed between the African and Chinese subjects. The AUCs of the African is about 4-10 fold higher than that of the Chinese for the three benzylisoquinoline alkaloids. Magnoflorine, an aporphine alkaloid, was absorbed better in the Chinese than in the African. The biotransformation of K-601 by human intestinal microflora was also investigated. The major reactions included hydroxylation, methylation, demethylation, acetylation and reduction. Glucuronidation and sulfation were not observed with fecal flora. These results may be important and useful in linking data from pharmacological assays and clinical effects. PMID:26268432

  10. Pharmacokinetics of a multicomponent herbal preparation in healthy Chinese and African volunteers.

    PubMed

    Alolga, Raphael N; Fan, Yong; Zhang, Gang; Li, Jin; Zhao, Yi-Jing; Lelu Kakila, Jimmy; Chen, Yan; Li, Ping; Qi, Lian-Wen

    2015-08-13

    K-601 is an herbal formulation for influenza consisting of Lonicera japonica, Isatis indigotica, Rheum palmatum, Phellodendron chinense, and Scutellaria baicalensis. In this work, we characterized the chemical constituents in K-601, identified the absorbed compounds and determined their pharmacokinetics in 6 Chinese and African volunteers by liquid chromatography with time-of-flight mass spectrometry. Similarity evaluation for chromatographic fingerprint of nine different batches showed values above 0.983. Totally, 50 components were identified in K-601. Then, 15 major prototype compounds and 17 metabolites were identified in human plasma. Major metabolic pathways included glucuronidation, sulfation, methylation, demethylation, and reduction. The pharmacokinetics of the most abundant prototype compounds, berberine, jatrorrhizine, palmatine and magnoflorine were determined. Significant pharmacokinetic differences were observed between the African and Chinese subjects. The AUCs of the African is about 4-10 fold higher than that of the Chinese for the three benzylisoquinoline alkaloids. Magnoflorine, an aporphine alkaloid, was absorbed better in the Chinese than in the African. The biotransformation of K-601 by human intestinal microflora was also investigated. The major reactions included hydroxylation, methylation, demethylation, acetylation and reduction. Glucuronidation and sulfation were not observed with fecal flora. These results may be important and useful in linking data from pharmacological assays and clinical effects.

  11. Fluorescence detection of tramadol in healthy Chinese volunteers by high-performance liquid chromatography and bioequivalence assessment

    PubMed Central

    Zhou, Xiao; Liu, Ji

    2015-01-01

    This study developed a revised high-performance liquid chromatography fluorescence method to determine plasma tramadol concentration, and thereby to examine the bioequivalence of two tramadol formulations among healthy male Chinese volunteers. The study used a double-blind, randomized, 2×2 crossover-design principle. Calculated pharmacokinetic parameters for both formulations were consistent with previous reports. According to the observation of vital signs and laboratory measurement, no subjects had any adverse reactions. The geometric mean ratios (90% confidence interval) of the test drug/reference drug for tramadol were 100.2% (95.3%–103.4%) for the area under the plasma concentration–time curve (AUC) from time zero to the last measurable concentration, 99.6% (94.2%–102.7%) for the AUC from administration to infinite time, and 100.8% (93.1%–106.4%) for maximum concentration. For the 90% confidence intervals of the test/reference AUC ratio and maximum concentration ratio of tramadol, both were in the acceptance range for bioequivalence. According to the two preparations by pharmacokinetic parameter statistics, the half-life, mean residence time, and clearance values showed no significant statistical differences. Therefore, the conclusion of this study was that the two tramadol formulations (tablets and capsules) were bioequivalent. PMID:25750519

  12. Pharmacokinetic profile of cefbuperazone in healthy Chinese volunteers after single and multiple drip intravenous infusion by HPLC-MS/MS.

    PubMed

    Liu, Dongbo; Geng, Taohua; Wang, Yiya; Ding, Li

    2016-09-10

    A selective and reproducible HPLC-MS/MS method was developed and fully validated for the determination of cefbuperazone in human plasma and urine. Samples were prepared using protein precipitation and separated on a Zorbax Eclipse Plus C18 column (2.1×50mm, 3.5μm). The API-4000 mass spectrometer was operated under multiple reaction monitoring mode (MRM) using the electrospray ionization technique. Linearity was achieved from 0.250 to 250μg/mL in plasma and 20.0-5000μg/mL in urine. The method was successfully applied to a pharmacokinetic study of cefbuperazone in healthy Chinese volunteers after drip intravenous infusion of 0.5, 1.0, 2.0g cefbuperazone sodium injection. Cefbuperazone reached a maximum concentration (Cmax) of 44.7±8.1μg/mL, 86.7±12.7μg/mL and 168±14μg/mL in 0.5, 1.0 and 2.0g dose groups respectively, at 60min after the start of infusion. The half-life (t1/2) was between 1.8-1.9h, and the elimination constant (kel) was between 0.36-0.39h(-1). The results proved that cefbuperazone showed linear pharmacokinetic profile in the dose range of 0.5-2.0g without gender difference. Drug accumulation was not observed. Cefbuperazone reached the maximum excretion rate in urine 2h after the start of infusion. About 60.0% of the administered drug was excreted via urine as unchanged form within 12h. The cumulative excretion of cefbuperazone after single drip intravenous infusion was proportional to the administered dose within the range from 0.5g to 2.0g. PMID:27394175

  13. Pharmacokinetics and bioequivalence study of escitalopram oxalate formulations after single-dose administration in healthy Chinese male volunteers.

    PubMed

    Li, Jing; Tian, Yuan; Zhang, Zun-Jian; Wang, Na; Ren, Xiaolei; Chen, Yun

    2009-01-01

    The aim of the present study was to compare the bioavailability of escitalopram (CAS 128196-01-0) from two escitalopram oxalate (CAS 219861-08-2) tablets (escitalopram 10 mg tablet as test preparation and 10 mg tablet commercially available original tablet of the drug as reference preparation) in 20 Chinese healthy male volunteers, aged between 19 and 27. The study was conducted according to an open, randomized, single blind, 2-way crossover study design with a wash-out phase of 14 d. Blood samples for pharmacokinetic profiling were taken up to 156 h post-dose, and escitalopram plasma concentrations were determined with a validated liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method. Maximum plasma concentrations (C(max)) of 9.85 +/- 1.79 ng/ml (test) and 9.92 +/- 2.14 ng/ml (reference) were achieved. Areas under the plasma concentration-time curve (AUC(0-infinity)) of 428.40 +/- 140.25 ng x h/ml (test) and 413.73 +/- 144.81 ng x h/ml (reference), AUC(0-t) of 401.33 +/- 120.61 ng x h/ml (test), 385.42 +/- 117.73 ng x h/ml (reference) were calculated. The median T(max) was 4.3 +/- 1.8h, 4.1 +/- 1.5 h for test and reference formulation, respectively. Plasma elimination half-lives (t 1/2) of 36.30 +/- 8.93 h (test), 36.70 +/- 9.99 h (reference) were determined. Both primary target parameters, AUC(0-infinity) and AUC(0-t) were tested parametrically by analysis of variance (ANOVA) and relative bioavailabilities were 105.1 +/- 10.8% for AUC(0-infinity), 104.9 +/- 11.1% for AUC(0-t). Bioequivalence between test and reference preparation was demonstrated for both parameters, AUC(0-infinity) and AUC(0-t). The 90% confidence intervals of the T/R-ratios of logarithmically transformed data were in the generally accepted range of 80%-125%. That means that the test formulation is bioequivalent to the reference formulation for escitalopram. PMID:19537522

  14. An indirect sandwich ELISA for the determination of agkisacutacin in human serum: application to pharmacokinetic study in Chinese healthy volunteers.

    PubMed

    Zhao, Ya-Nan; Dai, Xiang-Rong; Liu, Juan-Juan; Li, Xiang-Hong; Yang, Jing-Jing; Sun, Hua; Wu, Ping; Shen, Jie; Lu, Jian-Ping; Xie, Hai-Tang; Liu, Xiao-Quan

    2012-11-01

    The platelet receptor glycoprotein Ib-IX-V complex (GPIb-IX-V) plays a dominant role in the first step of platelet adhesion and arterial thrombus formation. Agkisacutacin, a C-type lectin-like protein (CLP) from Agkistrodon acutus venom, had been previously identified as an antagonist of platelet aggregation and a membrane glycoprotein Ib-binding protein (GPIb-bp). For the analysis of pharmacokinetics of agkisacutacin, an indirect sandwich enzyme-linked immunosorbent assay (ELISA) was established and validated to quantify agkisacutacin in human serum. The method was precise and accurate over the entire linear range of 1.0 and 1000 pg/mL with a lower limit of quantification of 1.0 pg/mL. The intra- and inter-assay coefficient of variation ranged from 0.7 to 4.2% and 1.1 to 4.1%, respectively. Recovery obtained from the accuracy test, using three concentration levels, varied between 96.1 and 110.6%, confirming the assay's reliability. The long-term study showed agkisacutacin was stable at -70 °C up to 46 days. This ELISA was first used to assess the pharmacokinetics of agkisacutacin in healthy volunteers. The characteristics of pharmacokinetic showed that agkisacutacin could rapidly combine with GPIb and slowly dissociate from GPIb-bound form in the body. PMID:22738788

  15. Pharmacokinetics and Bioequivalence of Two Formulations of Febuxostat 40-Mg and 80-Mg Tablets: A Randomized, Open-Label, 4-Way Crossover Study in Healthy Chinese Male Volunteers

    PubMed Central

    Luo, Zhu; Nan, Feng; Miao, Jia; Chen, Zhihui; Li, Mei; Liang, Maozhi

    2016-01-01

    The present study aimed to investigate the pharmacokinetic properties of febuxostat in healthy Chinese male volunteers and evaluate whether the two formulations of febuxostat 40-mg and 80-mg tablets are bioequivalent. A randomized, open-label, 4-way crossover study was conducted in healthy Chinese male volunteers under fasting conditions. 24 eligible subjects were randomized in a 1:1:1:1 ratio to receive a single dose of test or reference formulation of febuxostat 40-mg or 80-mg tablet. The washout period between each administration was 1 week. Plasma febuxostat was quantified by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Tolerability was evaluated by monitoring adverse events, physical examinations, 12-lead ECG and laboratory tests. After single-dosing of 1 tablet of 40-mg febuxostat, the pharmacokinetic parameters of test and reference formulations were: Tmax 1.22±0.87 and 1.85±1.03 h, Cmax 1689.16±461.31 and 1613.80±608.43 ng·mL-1, AUC0-t 5139.87±1349.28 and 5517.91±2024.26 ng·mL-1·h, AUC0−∞ 5263.06±1339.16 and 5640.48±2040.22 ng·mL-1·h, t1/2 4.82±2.61 and 4.85±1.78 h, respectively. After single-dosing of 1 tablet of 80-mg febuxostat, the pharmacokinetic parameters of test and reference formulations were: Tmax 1.71±1.21 and 2.23±1.55 h, Cmax 2744.47±1157.44 and 2998.17±1200.13 ng·mL-1, AUC0-t 9634.03±2768.25 and 10467.95±3501.65 ng·mL-1·h, AUC0−∞ 9834.32±2730.51 and 10626.63±3504.08 ng·mL-1·h, t1/2 6.25±2.44 and 5.46±1.65 h, respectively. For single-dosing of 1 tablet of 40-mg febuxostat, 90% CIs for the test/reference ratio of AUC0-t, AUC0−∞ and Cmax were 89.79 to 102.55, 90.14 to 102.56 and 93.99 to 129.63, respectively. For single-dosing of 1 tablet of 80-mg febuxostat, 90% CIs for the test/reference ratio of AUC0-t, AUC0−∞ and Cmax were 86.67 to 100.00, 87.50 to 100.51 and 79.48 to 105.99, respectively. This single dose study revealed similar pharmacokinetic properties in

  16. Effects of an Al3+- and Mg2+-containing antacid, ferrous sulfate, and calcium carbonate on the absorption of nemonoxacin (TG-873870) in healthy Chinese volunteers

    PubMed Central

    Zhang, Yi-fan; Dai, Xiao-jian; Wang, Ting; Chen, Xiao-yan; Liang, Li; Qiao, Hua; Tsai, Cheng-yuan; Chang, Li-wen; Huang, Ping-ting; Hsu, Chiung-yuan; Chang, Yu-ting; Tsai, Chen-en; Zhong, Da-fang

    2014-01-01

    Aim: To evaluate the effects of an Al3+- and Mg2+-containing antacid, ferrous sulfate, and calcium carbonate on the absorption of nemonoxacin in healthy humans. Methods: Two single-dose, open-label, randomized, crossover studies were conducted in 24 healthy male Chinese volunteers (12 per study). In Study 1, the subjects orally received nemonoxacin (500 mg) alone, or an antacid (containing 318 mg of Al3+ and 496 mg of Mg2+) plus nemonoxacin administered 2 h before, concomitantly or 4 h after the antacid. In Study 2, the subjects orally received nemonoxacin (500 mg) alone, or nemonoxacin concomitantly with ferrous sulfate (containing 60 mg of Fe2+) or calcium carbonate (containing 600 mg of Ca2+). Results: Concomitant administration of nemonoxacin with the antacid significantly decreased the area under the concentration-time curve from time 0 to infinity (AUC0–∞) for nemonoxacin by 80.5%, the maximum concentration (Cmax) by 77.8%, and urine recovery (Ae) by 76.3%. Administration of nemonoxacin 4 h after the antacid decreased the AUC0–∞ for nemonoxacin by 58.0%, Cmax by 52.7%, and Ae by 57.7%. Administration of nemonoxacin 2 h before the antacid did not affect the absorption of nemonoxacin. Administration of nemonoxacin concomitantly with ferrous sulfate markedly decreased AUC0–∞ by 63.7%, Cmax by 57.0%, and Ae by 59.7%, while concomitant administration of nemonoxacin with calcium carbonate mildly decreased AUC0–∞ by 17.8%, Cmax by 14.3%, and Ae by 18.4%. Conclusion: Metal ions, Al3+, Mg2+, and Fe2+ markedly decreased the absorption of nemonoxacin in healthy Chinese males, whereas Ca2+ had much weaker effects. To avoid the effects of Al3+ and Mg2+-containing drugs, nemonoxacin should be administered ≥2 h before them. PMID:25327812

  17. Sumatriptan and cerebral perfusion in healthy volunteers.

    PubMed

    Scott, A K; Grimes, S; Ng, K; Critchley, M; Breckenridge, A M; Thomson, C; Pilgrim, A J

    1992-04-01

    1. The effect of sumatriptan on regional cerebral perfusion was studied in healthy volunteers. 2. Intravenous sumatriptan (2 mg) had no detectable effect on regional cerebral perfusion as measured using a SPECT system with 99technetiumm labelled hexemethylpropyleneamineoxime. 3. Sumatriptan had no effect on pulse, blood pressure or ECG indices. 4. All six volunteers experienced minor adverse effects during the intravenous infusion.

  18. A rapid and sensitive LC-MS/MS method for determination of lercanidipine in human plasma and its application in a bioequivalence study in Chinese healthy volunteers.

    PubMed

    Li, Xiaobing; Shi, Fuguo; He, Xiaojing; Jian, Lingyan; Ding, Li

    2016-09-01

    A rapid and highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the determination of lercanidipine (LER) in human plasma. The plasma sample was deproteinized with methanol after addition of diazepam (internal standard, IS) and separated on a 38°C Hedera ODS-2 analytical column with a mobile phase of methanol and 5mM ammonium acetate buffer solution containing 0.1% formic acid at an isocratic flow rate of 400μL/min. The detection was performed on an API 4000 tandem mass spectrometer coupled with electrospray ionization (ESI) source in positive ESI mode. Quantification was conducted by multiple reaction monitoring (MRM) of the transitions of m/z 612.2→280.2 for LER and m/z 285.1→193.1 for IS, respectively. The method exhibited high sensitivity (LLOQ of 0.015ng/mL) and good linearity over the concentration range of 0.015-8.0ng/mL. No matrix effect and carry-over effect were observed. The values on both the occasions (intra- and inter-day) were all within 15% at three concentration levels. This robust method was successfully applied in a bioequivalence study to evaluate the pharmacokinetics of LER in 59 healthy male Chinese volunteers after a single oral administration of 10mg LER. PMID:27232153

  19. LC-MS/MS determination and urinary excretion study of seven alkaloids in healthy Chinese volunteers after oral administration of Shuanghua Baihe tablets.

    PubMed

    Cheng, Minlu; Liu, Ruijuan; Wu, Yao; Gu, Pan; Zheng, Lu; Liu, Yujie; Ma, Pengcheng; Ding, Li

    2016-01-25

    An LC-MS/MS method was developed and validated for the simultaneous determination of magnoflorine, berberrubine, jatrorrhizine, coptisine, epiberberine, palmatine and berberine in human urine. The sample preparation procedure involved the four-fold dilution of the urine samples with acetonitrile/water (1:3, v/v). The chromatographic separation was achieved on a Hedera ODS-2 column under gradient elution at a flow rate of 0.4 mL/min with acetonitrile and water containing 0.5% formic acid as the mobile phase. The mass detection was performed in the positive mode. Calibration curves of the seven alkaloids showed good linearity (correlation coefficients>0.9973) over their concentration ranges. To meet the requirements of urinary excretion study for each alkaloid in human, the lower limit of quantification was set at different values from 0.05063 ng/mL to 2.034 ng/mL for the seven alkaloids, respectively. The intra- and inter-batch precision and accuracy were all within ± 15%. No matrix effect was observed for the analytes. The validated method was applied to the excretion study for the seven alkaloids in healthy Chinese volunteers after oral administration of Shuanghua Baihe tablets. The average 72 h cumulative urinary excretion of magnoflorine, berberrubine, jatrorrhizine, coptisine, epiberberine, palmatine and berberine accounted for 1.81%, 0.27%, 0.29%, 0.046%, 0.027%, 0.010% and 0.021% of the respective administered dose.

  20. Healthy Volunteer 2020: Comparing Peace Corps Volunteers' health metrics with Healthy People 2020 national objectives.

    PubMed

    Henderson, Susan J; Newman, Jeannette; Ferguson, Rennie W; Jung, Paul

    2016-12-01

    Healthy People 2020 (HP2020) provides a set of quantifiable objectives for improving the health and well-being of Americans. This study examines Peace Corps Volunteers' health metrics in comparison with the Leading Health Indicators (LHIs) in order to set baseline measures for Volunteers' health care and align our measurements with Healthy People 2020 standards. Health data from multiple internal Peace Corps datasets were compared with relevant LHIs and analyzed using descriptive statistics. Seventeen (65%) of the 26 LHIs were relevant to Peace Corps Volunteers. Of these, Volunteers' health measures met or were more favorable than the goals of 13 (76%) of the LHIs. There were no data available for 4 (24%) of the LHIs. The entire Volunteer population has full access to primary care, oral health, and reproductive health services. No suicides or homicides were reported among Volunteers during the analyzed time period. Utilizing the LHIs, we have identified high-priority public health issues relevant for the Peace Corps Volunteer population. We discuss the need for quality data to measure and monitor Volunteers' health progress and outcomes over time, and also to standardize our measurements with Healthy People 2020 benchmarks. This framework may foster greater collaboration to engage in health promotion and disease prevention activities driven by evidence-based information, which may, in turn, encourage healthy behavior among Volunteers.

  1. A replicate designed bioequivalence study to compare two fixed-dose combination products of artesunate and amodiaquine in healthy chinese volunteers.

    PubMed

    Liu, Yun; Hu, Chaoying; Liu, Gangyi; Jia, Jingying; Yu, Chen; Zhu, Jianmin; Zheng, Qingsi; Zhang, Kanyin E

    2014-10-01

    Artesun-Plus is a fixed-dose combination antimalarial agent containing artesunate and amodiaquine. The current study was conducted to compare the pharmacokinetic and safety profiles of Artesun-Plus and the WHO-designated comparator product Artesunate Amodiaquine Winthrop. To overcome the high intrasubject variability of artesunate, the study applied a two-sequence and four-period crossover (2 by 4), replicate study design to assess bioequivalence between the two products in 31 healthy male Chinese volunteers under fasting conditions. The results showed that the values of the geometric mean ratios of maximum concentration of drug in plasma (Cmax) and area under the concentration-time curve from time zero to the last blood sample collection (AUC0-last) for the artesunate component in the test and reference products were 95.9% and 93.9%, respectively, and that the corresponding 90% confidence intervals were 84.5% to 108.7% and 87.2% to 101.1%, while the geometric mean ratios for the amodiaquine component in the test and reference products were 95.0% and 100.0%, respectively, and the corresponding 90% confidence intervals were 86.7% to 104.1% and 93.5% to 107.0%. In conclusion, bioequivalence between the two artesunate and amodiaquine fixed-dose combination products was demonstrated for both components. The study also confirmed high intrasubject variability, especially for artesunate: the coefficients of variation (CV) of Cmax values for the test and reference products were 39.2% and 43.7%, respectively, while those for amodiaquine were 30.6% and 30.2%, respectively.

  2. Pharmacokinetic Interaction Study of Ranitidine and Daijokito in Healthy Volunteers

    PubMed Central

    Endo, Yusuke; Ishihara, Yoshitaka; Tsuno, Satoshi; Matsuda, Akiko; Qian, Weibin; Miura, Norimasa; Hasegawa, Junichi

    2016-01-01

    Background Ranitidine is a histamine 2 receptor antagonist, and daijokito is a Kampo (Chinese herbal medicine as practiced in Japan) formula, which is traditionally used for treating constipation and digestive trouble. Previous study demonstrated that daijokito significantly affected the pharmacokinetics of ranitidine in rats; however, the doses of ranitidine and daijokito in that study were higher than in clinical practice. Therefore, we examined the pharmacokinetic interaction between ranitidine and daijokito in clinical practice doses in healthy volunteers. Methods This was a randomized, open label, two-period crossover study in healthy volunteers (n = 7). Volunteers received administrations of either a single dose of ranitidine 300 mg, or ranitidine 300 mg in combination with daijokito extract granules 2.5 g. Plasma concentrations of ranitidine were measured over 12 h by LC/MS/MS method. Results Plasma concentrations of ranitidine were lower with co-administration of daijokito compared with ranitidine alone. Co-administration of daijokito significantly decreased ranitidine area under the plasma concentration-time curve from 0 to 12 h (AUC0–12) and maximum plasma concentration (Cmax) with geometric mean (GM) ratio [90% confidence interval (CI)] for AUC0–12 of 0.609 (0.449, 0.826) and Cmax of 0.515 (0.345, 0.771). Conclusion Co-administration of ranitidine with daijokito resulted in a significant decrease in plasma level of ranitidine in healthy volunteers. PMID:27493481

  3. Pharmacokinetics study of amoxycillin and clavulanic acid (8:1)--a new combination in healthy Chinese adult male volunteers using the LC-MS/MS method.

    PubMed

    Zhang, Juanhong; Wang, Yinfu; Xie, Hua; Wang, Rong; Jia, Zhengping; Men, Xiandong; Xu, Liting; Zhang, Qiang

    2013-04-01

    New oral granules of amoxicillin and clavulanic acid in 8:1 ratio have recently been developed and approved to conduct clinical trial in China. To date, there has been no report studying the pharmacokinetic characteristics of amoxicillin and clavulanic acid in man. Therefore, it is urgent to investigate the pharmacokinetic properties of amoxicillin and clavulanic acid in man. The aim of the study was to assess the pharmacokinetic properties of amoxicillin and clavulanic acid in 8:1 with different dosage in healthy volunteers and provide support for this drug to obtain marketing authorization in China. A liquid chromatography-tandem mass spectrometry method for determining the concentration of amoxicillin and clavulanic acid in human plasma was developed and applied to this open-label, single- and multiple-dose Pharmacokinetics study. Subjects were randomized to receive a single dose of 1, 2, and 4 pouches of the test granulation of amoxicillin and clavulanic acid in 8:1 ratio (amoxicillin is 250 mg and clavulanic acid is 31.25 mg per pouch). In the single-dose phase, blood samples were collected before dosing and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 5, 8, 12, and 24 h after drug administration. In the multiple-dose phase, samples were obtained before drug administration on days 1, 2, 3, and 4 to determine the Cmin of amoxicillin and clavulanic acid. In the 4th day, samples were collected from 0.25 to 24 h after drug administration. Profiles of the concentration-time curves of amoxicillin and clavulanic acid were best fitted to two-compartment model. In this group of healthy Chinese subjects, the pharmacokinetics of amoxicillin fitted the linear dynamic feature at doses of 250,500 and 1,000 mg, and not obviously about clavulanic acid at doses of 31.25, 62.5, and 125 mg. The t 1/2 of single dose and multidoses were (1.45 ± 0.12) and (1.44 ± 0.26) h of amoxicillin and (1.24 ± 0.23) and (1.24 ± 0.17) of clavulanic acid, respectively; The AUC0-24 of single dose

  4. Pharmacokinetics of Oral Taurine in Healthy Volunteers

    PubMed Central

    Ghandforoush-Sattari, Mohammadreza; Mashayekhi, Siminozar; Krishna, Channarayapatna V.; Thompson, John P.; Routledge, Philipp A.

    2010-01-01

    Taurine, a sulfur-containing amino acid, is a normal constituent of the human diet. Little is known of the pharmacokinetics of taurine in man after oral administration. We studied the pharmacokinetics of 4 g taurine in eight healthy male volunteers (median age 27.5, range 22–45) following orally administration in the fasting state in the morning. Blood samples were taken at regular intervals and plasma taurine concentration was measured by a modified HPLC method. Data were subjected to noncompartmental analysis. Maximum plasma taurine concentration (Cmax) was measured at 1.5 ± 0.6 hr after administration as 86.1 ± 19.0 mg/L (0.69 ± 0.15 mmol). Plasma elimination half-life (T1/2) and the ratio of clearance/bioavailability (Cl/F) were 1.0 ± 0.3 hr and 21.1 ± 7.8 L/hr, respectively. Since taurine is occasionally used in therapeutics as a medicine, the pharmacokinetics and effects of oral taurine in healthy volunteers would be useful in the future studies of taurine in pharmacology and nutrition. PMID:22331997

  5. Urethral pressure variations in healthy male volunteers.

    PubMed

    Kirkeby, H J; Sørensen, S; Poulsen, E U

    1989-01-01

    Urethral pressures are usually considered to be static and only few authors have emphasized time-related pressure changes. We conducted a study on 10 healthy male volunteers, monitoring the urethral pressures at maximal urethral closure pressure, 2.5 cm proximal (bladder neck) and 2.5 cm distal (pars bulbosa) respectively over 30 min periods. At the bladder neck only sporadic waves were seen. At maximal closure pressure almost permanent oscillations were found, the wavelengths and amplitudes showing big differences. At the pars bulbosa 2 persons showed only sporadic oscillations and in 7 we found permanent pressure variations. The pressure variations are proposed to represent peristaltic activity with the ability of expelling the last drops of urine after micturition and posing a mechanical barrier to ascending microorganisms. PMID:2749948

  6. Pharmacogenetics of healthy volunteers in Puerto Rico.

    PubMed

    Claudio-Campos, Karla; Orengo-Mercado, Carmelo; Renta, Jessicca Y; Peguero, Muriel; García, Ricardo; Hernández, Gabriel; Corey, Susan; Cadilla, Carmen L; Duconge, Jorge

    2015-12-01

    Puerto Ricans are a unique Hispanic population with European, Native American (Taino), and higher West African ancestral contributions than other non-Caribbean Hispanics. In admixed populations, such as Puerto Ricans, genetic variants can be found at different frequencies when compared to parental populations and uniquely combined and distributed. Therefore, in this review, we aimed to collect data from studies conducted in healthy Puerto Ricans and to report the frequencies of genetic polymorphisms with major relevance in drug response. Filtering for healthy volunteers or individuals, we performed a search of pharmacogenetic studies in academic literature databases without limiting the period of the results. The search was limited to Puerto Ricans living in the island, excluding those studies performed in mainland (United States). We found that the genetic markers impacting pharmacological therapy in the areas of cardiovascular, oncology, and neurology are the most frequently investigated. Coincidently, the top causes of mortality in the island are cardiovascular diseases, cancer, diabetes, Alzheimer's disease, and stroke. In addition, polymorphisms in genes that encode for members of the CYP450 family (CYP2C9, CYP2C19, and CYP2D6) are also available due to their relevance in the metabolism of drugs. The complex genetic background of Puerto Ricans is responsible for the divergence in the reported allele frequencies when compared to parental populations (Africans, East Asians, and Europeans). The importance of reporting the findings of pharmacogenetic studies conducted in Puerto Ricans is to identify genetic variants with potential utility among this genetically complex population and eventually move forward the adoption of personalized medicine in the island. PMID:26501165

  7. Pharmacogenetics of healthy volunteers in Puerto Rico.

    PubMed

    Claudio-Campos, Karla; Orengo-Mercado, Carmelo; Renta, Jessicca Y; Peguero, Muriel; García, Ricardo; Hernández, Gabriel; Corey, Susan; Cadilla, Carmen L; Duconge, Jorge

    2015-12-01

    Puerto Ricans are a unique Hispanic population with European, Native American (Taino), and higher West African ancestral contributions than other non-Caribbean Hispanics. In admixed populations, such as Puerto Ricans, genetic variants can be found at different frequencies when compared to parental populations and uniquely combined and distributed. Therefore, in this review, we aimed to collect data from studies conducted in healthy Puerto Ricans and to report the frequencies of genetic polymorphisms with major relevance in drug response. Filtering for healthy volunteers or individuals, we performed a search of pharmacogenetic studies in academic literature databases without limiting the period of the results. The search was limited to Puerto Ricans living in the island, excluding those studies performed in mainland (United States). We found that the genetic markers impacting pharmacological therapy in the areas of cardiovascular, oncology, and neurology are the most frequently investigated. Coincidently, the top causes of mortality in the island are cardiovascular diseases, cancer, diabetes, Alzheimer's disease, and stroke. In addition, polymorphisms in genes that encode for members of the CYP450 family (CYP2C9, CYP2C19, and CYP2D6) are also available due to their relevance in the metabolism of drugs. The complex genetic background of Puerto Ricans is responsible for the divergence in the reported allele frequencies when compared to parental populations (Africans, East Asians, and Europeans). The importance of reporting the findings of pharmacogenetic studies conducted in Puerto Ricans is to identify genetic variants with potential utility among this genetically complex population and eventually move forward the adoption of personalized medicine in the island.

  8. Pharmacogenetics of healthy volunteers in Puerto Rico

    PubMed Central

    Claudio-Campos, Karla; Orengo-Mercado, Carmelo; Renta, Jessicca Y.; Peguero, Muriel; García, Ricardo; Hernández, Gabriel; Corey, Susan; Cadilla, Carmen L.; Duconge, Jorge

    2016-01-01

    Puerto Ricans are a unique Hispanic population with European, Native American (Taino), and higher West African ancestral contributions than other non-Caribbean Hispanics. In admixed populations, such as Puerto Ricans, genetic variants can be found at different frequencies when compared to parental populations and uniquely combined and distributed. Therefore, in this review, we aimed to collect data from studies conducted in healthy Puerto Ricans and to report the frequencies of genetic polymorphisms with major relevance in drug response. Filtering for healthy volunteers or individuals, we performed a search of pharmacogenetic studies in academic literature databases without limiting the period of the results. The search was limited to Puerto Ricans living in the island, excluding those studies performed in mainland (United States). We found that the genetic markers impacting pharmacological therapy in the areas of cardiovascular, oncology, and neurology are the most frequently investigated. Coincidently, the top causes of mortality in the island are cardiovascular diseases, cancer, diabetes, Alzheimer’s disease, and stroke. In addition, polymorphisms in genes that encode for members of the CYP450 family (CYP2C9, CYP2C19, and CYP2D6) are also available due to their relevance in the metabolism of drugs. The complex genetic background of Puerto Ricans is responsible for the divergence in the reported allele frequencies when compared to parental populations (Africans, East Asians, and Europeans). The importance of reporting the findings of pharmacogenetic studies conducted in Puerto Ricans is to identify genetic variants with potential utility among this genetically complex population and eventually move forward the adoption of personalized medicine in the island. PMID:26501165

  9. Prediction of pain sensitivity in healthy volunteers

    PubMed Central

    Ravn, Pernille; Frederiksen, Rune; Skovsen, Anders P; Christrup, Lona L; Werner, Mads U

    2012-01-01

    Purpose The primary objective of the present study was to evaluate predictive parameters of the acute pain score during induction of an inflammatory heat injury. Patients and methods Healthy volunteers (50 females/50 males) were included in the study. The predictive potential of gender, anthropometric (body surface area, body mass index), psychological (anxiety, depression, vulnerability), and psychophysical (quantitative sensory testing, conditioned pain modulation) variables in estimating the pain response to a validated heat injury (47°C, 7 minutes, area 12.5 cm2) were investigated. All assessments were made in duplicate sessions separated by 21 days (median). Results There were three main findings in this study. First, a predictive model of pain sensitivity during the heat injury, including both genders and using multiple regression technique, could account for 28% of the variance (P < 0.0001), but gender-related differences in the final model could not be demonstrated. Second, the results confirmed significant gender-related differences in perception of electrical, pressure, and cold pressor stimuli (P < 0.002). Third, positive correlations between anthropometric data and pain perception during electrical and pressure stimuli were demonstrated (P < 0.001 and P < 0.005, respectively). Conclusion The study demonstrated predictability of acute pain sensitivity, and although gender-related differences in pain perception were demonstrated, no gender-related differences in pain sensitivity could be shown. Interestingly, positive correlations between anthropometric data and pain perception were shown for the first time. PMID:23055774

  10. Prediction of Psilocybin Response in Healthy Volunteers

    PubMed Central

    Studerus, Erich; Gamma, Alex; Kometer, Michael; Vollenweider, Franz X.

    2012-01-01

    Responses to hallucinogenic drugs, such as psilocybin, are believed to be critically dependent on the user's personality, current mood state, drug pre-experiences, expectancies, and social and environmental variables. However, little is known about the order of importance of these variables and their effect sizes in comparison to drug dose. Hence, this study investigated the effects of 24 predictor variables, including age, sex, education, personality traits, drug pre-experience, mental state before drug intake, experimental setting, and drug dose on the acute response to psilocybin. The analysis was based on the pooled data of 23 controlled experimental studies involving 409 psilocybin administrations to 261 healthy volunteers. Multiple linear mixed effects models were fitted for each of 15 response variables. Although drug dose was clearly the most important predictor for all measured response variables, several non-pharmacological variables significantly contributed to the effects of psilocybin. Specifically, having a high score in the personality trait of Absorption, being in an emotionally excitable and active state immediately before drug intake, and having experienced few psychological problems in past weeks were most strongly associated with pleasant and mystical-type experiences, whereas high Emotional Excitability, low age, and an experimental setting involving positron emission tomography most strongly predicted unpleasant and/or anxious reactions to psilocybin. The results confirm that non-pharmacological variables play an important role in the effects of psilocybin. PMID:22363492

  11. Prediction of psilocybin response in healthy volunteers.

    PubMed

    Studerus, Erich; Gamma, Alex; Kometer, Michael; Vollenweider, Franz X

    2012-01-01

    Responses to hallucinogenic drugs, such as psilocybin, are believed to be critically dependent on the user's personality, current mood state, drug pre-experiences, expectancies, and social and environmental variables. However, little is known about the order of importance of these variables and their effect sizes in comparison to drug dose. Hence, this study investigated the effects of 24 predictor variables, including age, sex, education, personality traits, drug pre-experience, mental state before drug intake, experimental setting, and drug dose on the acute response to psilocybin. The analysis was based on the pooled data of 23 controlled experimental studies involving 409 psilocybin administrations to 261 healthy volunteers. Multiple linear mixed effects models were fitted for each of 15 response variables. Although drug dose was clearly the most important predictor for all measured response variables, several non-pharmacological variables significantly contributed to the effects of psilocybin. Specifically, having a high score in the personality trait of Absorption, being in an emotionally excitable and active state immediately before drug intake, and having experienced few psychological problems in past weeks were most strongly associated with pleasant and mystical-type experiences, whereas high Emotional Excitability, low age, and an experimental setting involving positron emission tomography most strongly predicted unpleasant and/or anxious reactions to psilocybin. The results confirm that non-pharmacological variables play an important role in the effects of psilocybin.

  12. Reboxetine promotes social bonding in healthy volunteers.

    PubMed

    Tse, Wai S; Bond, Alyson J

    2003-06-01

    Reboxetine is a novel antidepressant with a selective action on noradrenaline. In addition to its efficacy in depression, it has been found to improve social adaptation. The objective of this study was to assess the specific social behavioural effects of reboxetine which might be associated with social adaptation. Ten pairs of healthy volunteers took part in a randomized double-blind, crossover study of 2 weeks treatment with reboxetine (4 mg b.d.) and placebo with a 2-week washout period. In each pair, one person (subject) took the tablets and the other (flatmate) received no treatment. On the last day of each treatment period, the subjects socially interacted with a stranger (a confederate behaving as a responsive person) in a stranger-dyadic social interaction paradigm. After the interaction, subjects played the Mixed-Motive game, which measures cooperative behaviour and communication, with the confederate. Subjects read a short story before and after the social interaction. The flatmates evaluated the social behaviour of the subjects before and at the end of the two treatment periods. On reboxetine, the subjects were rated to be significantly more agreeable and cooperative (passive participant) and less submissive by their flatmates. They showed significantly less eye contact with the confederate in the social interaction paradigm and gave significantly fewer helplessness messages during the game. They spoke faster on the reading task after the social interaction. This study provides evidence that reboxetine increases cooperative social behaviour and increases social drive, which might be important for social adaptation.

  13. Non-invasive assessment of phosphate metabolism and oxidative capacity in working skeletal muscle in healthy young Chinese volunteers using 31P Magnetic Resonance Spectroscopy

    PubMed Central

    Wang, Huiting; Wu, Wenbo; Zhang, Xin; Tian, Chuanshuai; Yu, Haiping; Liu, Renyuan; Zhu, Bin

    2016-01-01

    Background. Generally, males display greater strength and muscle capacity than females while performing a task. Muscle biopsy is regarded as the reference method of evaluating muscle functions; however, it is invasive and has sampling errors, and is not practical for longitudinal studies and dynamic measurement during excise. In this study, we built an in-house force control and gauge system for quantitatively applying force to quadriceps while the subjects underwent 31P Magnetic Resonance Spectroscopy (31P-MRS); our aim was to investigate if there is a sex difference of phosphate metabolite change in working muscles in young heathy Chinese volunteers. Methods. Volunteers performed knee-extending excises using a force control and gauge system while lying prone in a Philips 3T Magnetic Resonance (MR) scanner. The 31P-MRS coil was firmly placed under the middle of the quadriceps . 31P-MRS measurements of inorganic phosphate (Pi), phosphocreatine (PCr) and adenosine triphosphate (ATP) were acquired from quadriceps while subjects were in a state of pre-, during- and post-exercise. The PCr, Pi, PCr/Pi, PCr/ATP, pH, work/energy cost ratio (WE), kPCr and oxidative capacity were compared between males and females. Results. A total of 17 volunteers underwent the study. Males: N = 10, age = 23.30 ± 1.25years; females: N = 7, age = 23.57 ± 0.79 years. In this study, males had significantly greater WE (16.33 ± 6.46 vs. 7.82 ± 2.16, p = 0.002) than females. Among PCr, Pi, PCr/Pi, PCr/ATP, pH, kPCr and oxidative capacity at different exercise status, only PCr/Pi (during-exercise, males = 5.630 ± 1.647, females = 4.014 ± 1.298, p = 0.047), PCr/ATP (during-exercise, males =1.273 ± 0.219, females = 1.523 ± 0.167, p = 0.025), and ATP (post-exercise, males = 24.469 ± 3.911 mmol/kg, females = 18.353 ± 4.818 mmol/kg, p = 0.035) had significant sex differences. Males had significantly greater PCr/Pi, but less PCr/ATP than females during exercise, suggesting males had higher

  14. Non-invasive assessment of phosphate metabolism and oxidative capacity in working skeletal muscle in healthy young Chinese volunteers using (31)P Magnetic Resonance Spectroscopy.

    PubMed

    Li, Ming; Chen, Fei; Wang, Huiting; Wu, Wenbo; Zhang, Xin; Tian, Chuanshuai; Yu, Haiping; Liu, Renyuan; Zhu, Bin; Zhang, Bing; Dai, Zhenyu

    2016-01-01

    Background. Generally, males display greater strength and muscle capacity than females while performing a task. Muscle biopsy is regarded as the reference method of evaluating muscle functions; however, it is invasive and has sampling errors, and is not practical for longitudinal studies and dynamic measurement during excise. In this study, we built an in-house force control and gauge system for quantitatively applying force to quadriceps while the subjects underwent (31)P Magnetic Resonance Spectroscopy ((31)P-MRS); our aim was to investigate if there is a sex difference of phosphate metabolite change in working muscles in young heathy Chinese volunteers. Methods. Volunteers performed knee-extending excises using a force control and gauge system while lying prone in a Philips 3T Magnetic Resonance (MR) scanner. The (31)P-MRS coil was firmly placed under the middle of the quadriceps . (31)P-MRS measurements of inorganic phosphate (Pi), phosphocreatine (PCr) and adenosine triphosphate (ATP) were acquired from quadriceps while subjects were in a state of pre-, during- and post-exercise. The PCr, Pi, PCr/Pi, PCr/ATP, pH, work/energy cost ratio (WE), kPCr and oxidative capacity were compared between males and females. Results. A total of 17 volunteers underwent the study. Males: N = 10, age = 23.30 ± 1.25years; females: N = 7, age = 23.57 ± 0.79 years. In this study, males had significantly greater WE (16.33 ± 6.46 vs. 7.82 ± 2.16, p = 0.002) than females. Among PCr, Pi, PCr/Pi, PCr/ATP, pH, kPCr and oxidative capacity at different exercise status, only PCr/Pi (during-exercise, males = 5.630 ± 1.647, females = 4.014 ± 1.298, p = 0.047), PCr/ATP (during-exercise, males =1.273 ± 0.219, females = 1.523 ± 0.167, p = 0.025), and ATP (post-exercise, males = 24.469 ± 3.911 mmol/kg, females = 18.353 ± 4.818 mmol/kg, p = 0.035) had significant sex differences. Males had significantly greater PCr/Pi, but less PCr/ATP than females during exercise, suggesting males had

  15. Vitamin K status in healthy volunteers.

    PubMed

    Theuwissen, E; Magdeleyns, E J; Braam, L A J L M; Teunissen, K J; Knapen, M H; Binnekamp, I A G; van Summeren, M J H; Vermeer, C

    2014-02-01

    Vitamin K's recommended dietary allowance (RDA) is based on the hepatic requirement for clotting factor synthesis, but substantial concentrations of undercarboxylated extra-hepatic Gla-proteins are found in the circulation of non-supplemented individuals. This suggests that vitamin K intake above the RDA is required for an optimal extra-hepatic vitamin K status. Circulating uncarboxylated osteocalcin (ucOC) and desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP) are considered markers of the vitamin K status in bone and the vasculature, respectively. We measured these markers in 896 samples of healthy volunteers and defined target groups for vitamin K supplementation based on increased levels indicative of tissue-specific vitamin K deficiency. We studied the response to vitamin K supplements at different states of vitamin K deficiency by measuring the circulating dp-ucMGP level in samples from two short-term trials on menaquinone-7 (MK-7, vitamin K2) supplementation in 42 children and 68 adults. Children had high ucOC levels (3.4-96.9 ng ml(-1)); other age groups had values in the range of 1.5-5.0 ng ml(-1). From the age of 40 years, dp-ucMGP levels gradually increased. Children and adults with more pronounced vitamin K deficiency gave the highest responses to MK-7 supplementation. Children and adults above 40 years showed the largest tissue-specific vitamin deficiency and accordingly may benefit from MK-7 supplementation to improve their extra-hepatic vitamin K status. PMID:24296867

  16. Limits on Risks for Healthy Volunteers in Biomedical Research

    PubMed Central

    Resnik, David B.

    2012-01-01

    Healthy volunteers in biomedical research often face significant risks in studies that offer them no medical benefits. The U.S. federal research regulations and laws adopted by other countries place no limits on the risks that these participants face. In this essay, I argue that there should be some limits on the risks for biomedical research involving healthy volunteers. Limits on risk are necessary to protect human participants, institutions, and the scientific community from harm. With the exception of self-experimentation, limits on research risks faced by healthy volunteers constitute a type of soft, impure paternalism, because participants usually do not fully understand the risks they are taking. I consider some approaches to limiting research risks and propose that healthy volunteers in biomedical research should not be exposed to greater than a 1% chance of serious harm, such as death, permanent disability, or severe illness or injury. While this guideline would restrict research risks, the limits would not be so low that they would prevent investigators from conducting valuable research. They would, however, set a clear upper boundary for investigators and signal to the scientific community and the public that there are limits on the risks that healthy participants may face in research. This standard provides guidance for decisions made by oversight bodies, but it is not an absolute rule. Investigators can enroll healthy volunteers in studies involving a greater than 1% chance of serious harm if they show that the research addresses a compelling public health or social problem and the risk of serious harm is only slightly more than 1%. The committee reviewing the research should use outside experts to assess these risks. PMID:22198413

  17. Psychometric Properties of the Volunteer Functions Inventory with Chinese Students

    ERIC Educational Resources Information Center

    Wu, Joseph; Lo, T. Wing; Liu, Elaine S. C.

    2009-01-01

    The authors report an evaluation of the psychometric properties of a Chinese version of the Volunteer Functions Inventory on a sample of university student volunteers. Reliabilities were high for four out of the six scales of the Inventory (Values, Career, Social, and Understanding) in terms of internal consistency. Items in these four scales also…

  18. An LC-MS/MS method for simultaneous determination of cefprozil diastereomers in human plasma and its application for the bioequivalence study of two cefprozil tablets in healthy Chinese volunteers.

    PubMed

    Liu, Min; Ma, Jing-Yi; Zhang, Yanan; Wang, Xiaolin; Zhao, Hongna; Du, Aihua; Yang, Man; Meng, Lingjie; Deng, Ming; Liu, Huichen

    2016-03-01

    A rapid and sensitive liquid chromatography-tandem mass spectrometric method was developed for the first time and validated for the determination of cefprozil diastereomers in human plasma. The plasma samples were prepared by protein precipitation using acetonitrile. Detection was performed using an electronic spray ion source in the negative ion mode, operating in the multiple reaction monitoring of the transitions m/z 388.0 to m/z 205.0 for cefprozil diastereomers and m/z 346.1 to m/z 268.1 for cephalexin (the internal standard). The calibration curves of cis-cefprozil and trans-cefprozil were linear in the ranges 0.125-16.0 µg/mL and 0.0403-1.72 µg/mL, respectively. The lower limits of quantification of cis- and trans-cefprozil were 0.125 and 0.0403 µg/mL in human plasma, respectively. The intra- and inter-day precisions of cis- and trans-cefprozil were all <9.7%, and the accuracy ranged from 99.2 to 104.7% and from 100.6 to 102.2%, respectively. The validated method was successfully applied to a bioequivalence study of two cefprozil formulations in 24 healthy Chinese volunteers. The two cefprozil tablets were bioequivalent by measurement of cis-, trans- and total cefprozil. We suggest that the bioequivalence of cefprozil formulations can be evaluated only using cis-cefprozil as the analyte in future studies. PMID:26129932

  19. Normal range values for thromboelastography in healthy adult volunteers.

    PubMed

    Scarpelini, S; Rhind, S G; Nascimento, B; Tien, H; Shek, P N; Peng, H T; Huang, H; Pinto, R; Speers, V; Reis, M; Rizoli, S B

    2009-12-01

    Thromboelastography (TEG) provides a functional evaluation of coagulation. It has characteristics of an ideal coagulation test for trauma, but is not frequently used, partially due to lack of both standardized techniques and normal values. We determined normal values for our population, compared them to those of the manufacturer and evaluated the effect of gender, age, blood type, and ethnicity. The technique was standardized using citrated blood, kaolin and was performed on a Haemoscope 5000 device. Volunteers were interviewed and excluded if pregnant, on anticoagulants or having a bleeding disorder. The TEG parameters analyzed were R, K, alpha, MA, LY30, and coagulation index. All volunteers outside the manufacturer's normal range underwent extensive coagulation investigations. Reference ranges for 95% for 118 healthy volunteers were R: 3.8-9.8 min, K: 0.7-3.4 min, alpha: 47.8-77.7 degrees, MA: 49.7-72.7 mm, LY30: -2.3-5.77%, coagulation index: -5.1-3.6. Most values were significantly different from those of the manufacturer, which would have diagnosed coagulopathy in 10 volunteers, for whom additional investigation revealed no disease (81% specificity). Healthy women were significantly more hypercoagulable than men. Aging was not associated with hypercoagulability and East Asian ethnicity was not with hypocoagulability. In our population, the manufacturer's normal values for citrated blood-kaolin had a specificity of 81% and would incorrectly identify 8.5% of the healthy volunteers as coagulopathic. This study supports the manufacturer's recommendation that each institution should determine its own normal values before adopting TEG, a procedure which may be impractical. Consideration should be given to a multi-institutional study to establish wide standard values for TEG.

  20. Diurnal variation in the quantitative EEG in healthy adult volunteers

    PubMed Central

    Cummings, L; Dane, A; Rhodes, J; Lynch, P; Hughes, A M

    2000-01-01

    Aims To define the change in power in standard waveband frequencies of quantitative cortical electroencephalogram (EEG) data over a 24 h period, in a drug free representative healthy volunteer population. Methods This was an open, non randomised study in which 18 volunteers (9 male and 9 female) were studied on 1 study day, over a 24 h period. Volunteers had a cortical EEG recording taken at 0, 2, 4, 6, 8, 10, 12, 16 and 24 h. Each recording lasted for 6 min (3 min eyes open, 3 min eyes closed). All EEG recordings were taken in a quietened ward environment with the curtains drawn round the bed and the volunteer supine. During the 3 min eyes open, volunteers were asked to look at a red circle on a screen at the foot of the bed, and refrain from talking. Results Plots produced of geometric mean power by time of the standard wave band frequencies gave some indication of a circadian rhythm over the 24 h period for θ (4.75–6.75 Hz), α1 (7.0–9.5 Hz) and β1 (12.75–18.50 Hz) wavebands. Mixed models were fitted to both the eyes open and eyes closed data which confirmed a change in mean waveband power with time with statistical significance at the conventional 5% level (P < 0.05). Conclusions These data indicate the presence of a diurnal variation in the cortical quantitative EEG. They support the use of a placebo control group when designing clinical trials which utilize quantitative EEG to screen for central nervous system (CNS) activity of pharmaceutical agents, to control for the confounding variable of time of day at which the EEG recordings were made. PMID:10886113

  1. Sodium Thiosulfate Pharmacokinetics in Hemodialysis Patients and Healthy Volunteers

    PubMed Central

    Stauffer, Emilie; Kalicki, Robert; Hildebrandt, Tatjana; Frey, Brigitte M.; Frey, Felix J.; Uehlinger, Dominik E.; Pasch, Andreas

    2011-01-01

    Summary Background and objectives Vascular calcification is a major cause of morbidity and mortality in dialysis patients. Human and animal studies indicate that sodium thiosulfate (STS) may prevent the progression of vascular calcifications. The pharmacokinetics of STS in hemodialysis patients has not been investigated yet. Design, setting, participants, & measurements STS was given intravenously to 10 hemodialysis patients on- and off-hemodialysis. Additionally, STS was applied to 9 healthy volunteers once intravenously and once orally. Thiosulfate concentrations were measured by using a specific and sensitive HPLC method. Results In volunteers and patients, mean endogenous thiosulfate baseline concentrations were 5.5 ± 1.82 versus 7.1 ± 2.7 μmol/L. Renal clearance was high in volunteers (1.86 ± 0.45 ml/min per kg) and reflected GFR. Nonrenal clearance was slightly, but not significantly, higher in volunteers (2.25 ± 0.32 ml/min per kg) than in anuric patients (2.04 ± 0.72 ml/min per kg). Hemodialysis clearance of STS was 2.62 ± 1.01 ml/min per kg. On the basis of the nonrenal clearance and the thiosulfate steady-state serum concentrations, a mean endogenous thiosulfate generation rate of 14.6 nmol/min per kg was calculated in patients. After oral application, only 4% of STS was recovered in urine of volunteers, reflecting a low bioavailability of 7.6% (0.8% to 26%). Conclusions Given the low and variable bioavailability of oral STS, only intravenous STS should be prescribed today. The biologic relevance of the high hemodialysis clearance for the optimal time point of STS dosing awaits clarification of the mechanisms of action of STS. PMID:21566113

  2. Bioavailability of ranitidine in healthy Mexican volunteers: effect of food.

    PubMed

    Juárez-Olguín, H; Flores, J; Pérez, G; Hernández, G; Flores, C; Guillé, A; Camacho, A; Toledo, A; Carrasco, M; Lares, I

    2002-01-01

    Is well known that food can affect the bioavailability of several drugs, its impact is major for those drugs that have to act near of drug absorption. Documentation about alterations of ranitidine bioavailability by effect of food is poor. The purpose of this work was to evaluate the effect of food over the bioavailability of ranitidine. Twenty healthy Mexican volunteers were included for the study. The study was made in two stages, in the first one the volunteers had 12 hour fast and took a 300 mg of oral dose of ranitidine (without food, WOF) and blood samples were drawn. Two weeks later, the volunteers took a normal diet just before ranitidine intake (with food, WF). The area under the curve (AUC) was 30% greater in WOF, Cmax was 921.5 ng/ml (WF) vs. 1685.2 (WOF), and t1/2 was 2.70 +/- 1.38 (WF) h vs 3.66 +/- 1.34 (WOF). The AUC, Cmax and t1/2 were statistically different. It is evident that there are differences in the drug disposition due to the presence of food, then, it is possible that the efficacy of ranitidine as inhibitor of gastric secretion being limited by food.

  3. Indomethacin and cognitive function in healthy elderly volunteers.

    PubMed

    Bruce-Jones, P N; Crome, P; Kalra, L

    1994-07-01

    1. Cognitive function was studied after single and multiple doses of indomethacin (I) and matched placebo (P) in 20 healthy elderly volunteers using a double-blind crossover design. 2. Arousal, attention, integration, coordination, memory and mood were investigated using a battery of psychomotor tests and the Hospital Anxiety and Depression Scale. Assessments were performed before and after the first and last doses of a 7 day course of medication. 3. Critical flicker fusion threshold fell by a mean of 1.96% on indomethacin compared with a 1.13% rise on placebo 5 h after the first dose (P = 0.029). A beneficial effect on choice reaction time latency (P = 0.012) was seen both after acute and continuing administration of indomethacin. Performance at the most discriminating level (level 3) of the paired word association test was significantly better following 8 days of treatment with indomethacin in the younger (55-65 year-old) age group (P = 0.001). 4. There was no significant difference in performance on the symbol-digit substitution test and the continuous attention task. No change was seen in hospital anxiety and depression scale scores. 5. These results suggest that performance on tests of sensorimotor coordination and short term memory may improve in healthy volunteers following indomethacin administration, whereas tests of attention and psychomotor speed remain unaffected. However, further controlled studies in rheumatic patients are needed to evaluate fully the psychomotor effects of indomethacin and other NSAIDs in clinical practice. PMID:7946936

  4. Is it appropriate regarding patient preference to take Myrtol standardized enteric-coated soft capsules after a meal rather than at fasted state? A food–drug pharmacokinetic interaction study in healthy Chinese volunteers

    PubMed Central

    Zhao, Ting-Ting; Zhu, Ling-Ling; Chen, Meng; Zhou, Quan

    2016-01-01

    Background According to prescribing information for Myrtol standardized enteric-coated soft capsules, the medicine should be taken on an empty stomach. Some patients may experience stomach discomfort after oral administration in fasted state and would prefer to take the medicine after a meal. However, there is no literature addressing the effect of meal on absorption of this drug; therefore, it is desirable to explore the feasibility of taking the capsule after a meal from pharmacokinetic perspective. Methods A gas chromatography coupled with triple quadruples mass spectrometry assay was established and validated for determining plasma concentrations of eucalyptol, a target component of Myrtol standardized capsules. A self-control clinical study was carried out in healthy male volunteers in fasted and fed states after a single oral dose of 300 mg capsules. Comparison of pharmacokinetic parameters in the two phases and bioequivalence evaluation were performed. Results The specificity, sensitivity, accuracy, and precision of the assay satisfied the requirements for biopharmaceutical analysis. Pharmacokinetic parameters of eucalyptol (fasted vs fed) were as follows: maximal plasma concentrations (Cmax) (167.60±114.69 vs 518.89±314.47 ng·mL−1), time of maximum concentration (Tmax) (3.7±1.1 vs 4.8±0.7 h), elimination half-life (T1/2) (3.2±1.4 vs 2.6±0.7 h), area under the plasma concentration–time curve (AUC0–t) (584.91±369.90 vs 1,271.61±605.82 ng·h·mL−1), and AUC0–∞ (690.36±467.26 vs 1,458.02±720.21 ng·h·mL−1). There was statistically significant difference in Cmax, AUC0–t, and AUC0–∞ between the two dosing methods (P<0.05). Pharmacokinetic parameters of eucalyptol given in fasted state in Chinese were comparable to those in Germany population. The 90% confidence intervals for the ratio of Cmax (18.4%~64.7%), AUC0–t (28.9%~68.5%), and AUC0–∞ (31.1%~68.4%) values for the test (fasted) and reference (fed) were beyond the Food and

  5. MDMA Impairs Response to Water Intake in Healthy Volunteers.

    PubMed

    Baggott, Matthew J; Garrison, Kathleen J; Coyle, Jeremy R; Galloway, Gantt P; Barnes, Allan J; Huestis, Marilyn A; Mendelson, John E

    2016-01-01

    Hyponatremia is a serious complication of 3,4-methylenedioxymethamphetamine (MDMA) use. We investigated potential mechanisms in two double-blind, placebo-controlled studies. In Study 1, healthy drug-experienced volunteers received MDMA or placebo alone and in combination with the alpha-1 adrenergic inverse agonist prazosin, used as a positive control to release antidiuretic hormone (ADH). In Study 2, volunteers received MDMA or placebo followed by standardized water intake. MDMA lowered serum sodium but did not increase ADH or copeptin, although the control prazosin did increase ADH. Water loading reduced serum sodium more after MDMA than after placebo. There was a trend for women to have lower baseline serum sodium than men, but there were no significant interactions with drug condition. Combining studies, MDMA potentiated the ability of water to lower serum sodium. Thus, hyponatremia appears to be a significant risk when hypotonic fluids are consumed during MDMA use. Clinical trials and events where MDMA use is common should anticipate and mitigate this risk. PMID:27403159

  6. MDMA Impairs Response to Water Intake in Healthy Volunteers

    PubMed Central

    Garrison, Kathleen J.; Coyle, Jeremy R.; Galloway, Gantt P.; Huestis, Marilyn A.; Mendelson, John E.

    2016-01-01

    Hyponatremia is a serious complication of 3,4-methylenedioxymethamphetamine (MDMA) use. We investigated potential mechanisms in two double-blind, placebo-controlled studies. In Study 1, healthy drug-experienced volunteers received MDMA or placebo alone and in combination with the alpha-1 adrenergic inverse agonist prazosin, used as a positive control to release antidiuretic hormone (ADH). In Study 2, volunteers received MDMA or placebo followed by standardized water intake. MDMA lowered serum sodium but did not increase ADH or copeptin, although the control prazosin did increase ADH. Water loading reduced serum sodium more after MDMA than after placebo. There was a trend for women to have lower baseline serum sodium than men, but there were no significant interactions with drug condition. Combining studies, MDMA potentiated the ability of water to lower serum sodium. Thus, hyponatremia appears to be a significant risk when hypotonic fluids are consumed during MDMA use. Clinical trials and events where MDMA use is common should anticipate and mitigate this risk. PMID:27403159

  7. CNS effects of sumatriptan and rizatriptan in healthy female volunteers.

    PubMed

    van der Post, J; Schram, M T; Schoemaker, R C; Pieters, M S M; Fuseau, E; Pereira, A; Baggen, S; Cohen, A F; van Gerven, J M A

    2002-05-01

    This study investigates the CNS effects of sumatriptan and rizatriptan, with temazepam as an active comparator, in healthy female volunteers. Sixteen volunteers completed a randomized, double-blind, crossover study and on four separate occasions received either 100 mg sumatriptan, 20 mg rizatriptan or 20 mg temazepam. The main parameters were eye movements, EEG, body sway, visual analogue scales and a cognitive test battery. Rizatriptan and sumatriptan decreased saccadic peak velocity by 18.3 (95% CI: 5.7, 30.8) and 15.0 (2.2, 27.9) degrees/sec, respectively, about half the decrease induced by temazepam (35.0 (22.1, 47.8) degrees/sec). Body sway increased (30% for rizatriptan (16%, 45%) and 14% for sumatriptan (1%, 27%), respectively). Temazepam caused larger, similar effects. In contrast to temazepam, sumatriptan and rizatriptan decreased reaction times of recognition tasks and increased EEG alpha power (significant for sumatriptan, 0.477 (0.02, 0.935). Therapeutic doses of sumatriptan and rizatriptan caused CNS effects indicative of mild sedation. For EEG and recognition reaction times the effects were opposite to temazepam, indicating central stimulation. PMID:12100089

  8. Shirodhara: A psycho-physiological profile in healthy volunteers

    PubMed Central

    Dhuri, Kalpana D.; Bodhe, Prashant V.; Vaidya, Ashok B.

    2013-01-01

    Background: Shirodhara is a classical and a well-established ayurvedic procedure of slowly and steadily dripping medicated oil or other liquids on the forehead. This procedure induces a relaxed state of awareness that results in a dynamic psycho-somatic balance. Objectives: The objective of the study is to evaluate the psychological and physiological effects of Shirodhara in healthy volunteers by monitoring the rating of mood and levels of stress, electrocardiogram (ECG), electroencephalogram (EEG), and selected biochemical markers of stress. Materials and Methods: The study was conducted in the human pharmacology laboratory. The study design was open labeled, comparing the baseline variables with values after Shirodhara. The subjects (n = 16) chosen were healthy human volunteers who gave an informed consent. Shirodhara was preceded by Abhyanga – whole body massage. The Shirodhara method was standardized for rate of dripping with peristaltic pump and temperature was controlled with a thermostat. Mood and stress levels were assessed by validated rating scales. The pre- and post-Shirodhara ECG and EEG records were evaluated. Results: Student's paired “t” test was applied to the means + SE of the variables to calculate statistical significance at P <0.05. There was a significant improvement in mood scores and the level of stress (P <0.001). These changes were accompanied by significant decrease in rate of breathing and reduction in diastolic blood pressure along with reduction in heart rate. The relaxed alert state, after Shirodhara, was co-related with an increase in alfa rhythm in EEG. Conclusion: A standardized Shirodhara leads to a state of alert calmness similar to the relaxation response observed in meditation. The clinical benefits observed with Shirodhara in anxiety neurosis, hypertension, and stress aggravation due to chronic degenerative diseases could be mediated through these adaptive physiological effects. PMID:23741161

  9. Pharmacogenetics in Central American healthy volunteers: interethnic variability.

    PubMed

    Céspedes-Garro, Carolina; Naranjo, María-Eugenia G; Ramírez, Ronald; Serrano, Víctor; Fariñas, Humberto; Barrantes, Ramiro; LLerena, Adrián

    2015-03-01

    Ethnicity is one of the major factors involved in interindividual variability to drug response. This study aims to describe the frequency of the most relevant pharmacogenetic biomarkers and metabolic phenotypes in Central American healthy volunteers and to determine its interethnic variability. Twenty-six original research articles on allelic, genotypes or metabolic phenotype frequencies were analyzed, in which a total number of 7611 Central American healthy volunteers were included (6118 were analyzed for genotype and 1799 for metabolic phenotype). No reports were available for population from Belize and Honduras. The CYP2D6*4 and *5 frequencies in Amerindian populations from Costa Rica have shown to be among the highest frequencies so far reported in the world. Furthermore, NAT2*5 and *6 presented higher frequencies in admixed populations than in Amerindians, but, inversely, the NAT2*7 was more frequent in Amerindians compared to an admixed population. Likewise, different patterns of distribution have been shown in HLA-A*02, *03 and HLA-B*07 among Native populations from Latin America. Reports on Central American populations were also found for the CYP2C19, LDLR, CYP2E1, MDR1, G6PD, TP53, CYP1A2, CYP3A4 and CYP3A5 biomarkers, but no data were available for the other 91 pharmacogenetic biomarkers revised in Central American populations. Differences in the frequency of some pharmacogenetic biomarkers and metabolic phenotypes were found, showing interethnic variability within Central American and with other Latin American populations. PMID:25490028

  10. Pharmacokinetic Interaction Between Prasugrel and Ritonavir in Healthy Volunteers

    PubMed Central

    Ancrenaz, Virginie; Déglon, Julien; Samer, Caroline; Staub, Christian; Dayer, Pierre; Daali, Youssef; Desmeules, Jules

    2013-01-01

    The new anti-aggregating agent prasugrel is bioactivated by cytochromes P450 (CYP) 3A and 2B6. Ritonavir is a potent CYP3A inhibitor and was shown in vitro as a CYP2B6 inhibitor. The aim of this open-label cross-over study was to assess the effect of ritonavir on prasugrel active metabolite (prasugrel AM) pharmacokinetics in healthy volunteers. Ten healthy male volunteers received 10 mg prasugrel. After at least a week washout, they received 100 mg ritonavir, followed by 10 mg prasugrel 2 hr later. We used dried blood spot sampling method to monitor prasugrel AM pharmacokinetics (Cmax, t1/2, tmax, AUC0–6 hr) at 0, 0.25, 0.5, 1, 1.5, 2, 4 and 6 hr after prasugrel administration. A ‘cocktail’ approach was used to measure CYP2B6, 2C9, 2C19 and 3A activities. In the presence of ritonavir, prasugrel AM Cmax and AUC were decreased by 45% (mean ratio: 0.55, CI 90%: 0.40–0.7, p = 0.007) and 38% (mean ratio: 0.62, CI 90%: 0.54–0.7, p = 0.005), respectively, while t1/2 and tmax were not affected. Midazolam metabolic ratio (MR) dramatically decreased in presence of ritonavir (6.7 ± 2.6 versus 0.13 ± 0.07) reflecting an almost complete inhibition of CYP3A4, whereas omeprazole, flurbiprofen and bupropion MR were not affected. These data demonstrate that ritonavir is able to block prasugrel CYP3A4 bioactivation. This CYP-mediated drug–drug interaction might lead to a significant reduction of prasugrel efficacy in HIV-infected patients with acute coronary syndrome. PMID:22900583

  11. Effect of transdermic acetylsalicylic acid on hemostasis in healthy volunteers.

    PubMed

    Martínez, Adriana B; Funosas, Esteban; Maestri, Lorella; Lucena, Perla Hermida

    2007-01-01

    Acetylsalicylic acid (ASA) exerts an antiaggregatory effect on platelets by irreversible inhibition of the enzyme thrombocyte cyclooxigenase when it is administered orally at doses above 80 mg/day. For several years ASA has been available as a solution that can be topically applied on the skin. It is widely used by athletes and individuals with chronic rheumatic disorders. However, it has not been established to date whether the plasma levels that result from these doses of ASA affect hemostasis during odontological procedures that involve bleeding, causing platelet dysfunction. The aim of the present study was to evaluate whether topical application is capable of affecting hemostasis. Three studies were conducted: A, B y C. Each of the 3 groups included 12 healthy volunteers of both sexes. The aim of study A was to evaluate if the formulation for topical application resulted in plasma levels of ASA that resembled those observed for the oral formulation and affect hemostasis. In experiment A, plasma levels of salicylic acid (SA) were assessed for each volunteer at 30 minutes, 60 minutes, 6 hours, 12 hours and 24 hours after oral administration of a dose of 500 mg ASA. Experiment B was identical to experiment A except for the fact that ASA was topically applied employing a commercial preparation Aspirub in a predetermined area at a rate of 2 ml/day over a period of 15 days. Experiment C was designed in the same way as experiment B, for a higher dose and a longer period of time (4 ml/day over a period of 30 days). One of the volunteers exhibited detectable salicylemia that could affect hemostasis as occurs with the oral formulation. The following two studies (C1 and C2) employed doses of Aspirub of 8 and 16 ml/day respectively, over a period of 30 days. We measured biochemical parameters associated to platelet function. The dose of 8 ml/day induced moderate alterations in all the parameters related to platelet function and the daily dose of 16 ml inhibited platelet

  12. Pharmacokinetic interaction between prasugrel and ritonavir in healthy volunteers.

    PubMed

    Ancrenaz, Virginie; Déglon, Julien; Samer, Caroline; Staub, Christian; Dayer, Pierre; Daali, Youssef; Desmeules, Jules

    2013-02-01

    The new anti-aggregating agent prasugrel is bioactivated by cytochromes P450 (CYP) 3A and 2B6. Ritonavir is a potent CYP3A inhibitor and was shown in vitro as a CYP2B6 inhibitor. The aim of this open-label cross-over study was to assess the effect of ritonavir on prasugrel active metabolite (prasugrel AM) pharmacokinetics in healthy volunteers. Ten healthy male volunteers received 10 mg prasugrel. After at least a week washout, they received 100 mg ritonavir, followed by 10 mg prasugrel 2 hr later. We used dried blood spot sampling method to monitor prasugrel AM pharmacokinetics (C(max) , t(1/2) , t(max) , AUC(0-6 hr) ) at 0, 0.25, 0.5, 1, 1.5, 2, 4 and 6 hr after prasugrel administration. A 'cocktail' approach was used to measure CYP2B6, 2C9, 2C19 and 3A activities. In the presence of ritonavir, prasugrel AM C(max) and AUC were decreased by 45% (mean ratio: 0.55, CI 90%: 0.40-0.7, p = 0.007) and 38% (mean ratio: 0.62, CI 90%: 0.54-0.7, p = 0.005), respectively, while t(1/2) and t(max) were not affected. Midazolam metabolic ratio (MR) dramatically decreased in presence of ritonavir (6.7 ± 2.6 versus 0.13 ± 0.07) reflecting an almost complete inhibition of CYP3A4, whereas omeprazole, flurbiprofen and bupropion MR were not affected. These data demonstrate that ritonavir is able to block prasugrel CYP3A4 bioactivation. This CYP-mediated drug-drug interaction might lead to a significant reduction of prasugrel efficacy in HIV-infected patients with acute coronary syndrome.

  13. Exercise increases endostatin in circulation of healthy volunteers

    PubMed Central

    Gu, Jian-Wei; Gadonski, Giovani; Wang, Julie; Makey, Ian; Adair, Thomas H

    2004-01-01

    Background Physical inactivity increases the risk of atherosclerosis. However, the molecular mechanisms of this relation are poorly understood. A recent report indicates that endostatin, an endogenous angiostatic factor, inhibits the progression of atherosclerosis, and suggests that reducing intimal and atherosclerotic plaque tissue neovascularization can inhibit the progression atherosclerosis in animal models. We hypothesize that exercise can elevate the circulatory endostatin level. Hence, exercise can protect against one of the mechanisms of atherosclerosis. Results We examined treadmill exercise tests in healthy volunteers to determine the effect of exercise on plasma levels of endostatin and other angiogenic regulators. Oxygen consumption (VO2) was calculated. Plasma levels of endostatin, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) were determined using ELISA. The total peak VO2 (L) in 7 male subjects was 29.5 ± 17.8 over a 4–10 minute interval of exercise. Basal plasma levels of endostatin (immediately before exercise) were 20.3 ± 3.2 pg/ml, the plasma levels increased to 29.3 ± 4.2, 35.2 ± 1.8, and 27.1 ± 2.2 ng/ml, at 0.5, 2, and 6 h, respectively, after exercise. There was a strong linear correlation between increased plasma levels of endostatin (%) and the total peak VO2 (L) related to exercise (R2 = 0.9388; P < 0.01). Concurrently, VEGF levels decreased to 28.3 ± 6.4, 17.6 ± 2.4, and 26.5 ± 12.5 pg/ml, at 0.5, 2, and 6 h, respectively, after exercise. There were no significant changes in plasma bFGF levels in those subjects before and after exercise. Conclusions The results suggest that circulating endostatin can be significantly increased by exercise in proportion to the peak oxygen consumption under physiological conditions in healthy volunteers. These findings may provide new insights into the molecular links between physical inactivity and the risk of angiogenesis dependent diseases such as

  14. Study of GABA in Healthy Volunteers: Pharmacokinetics and Pharmacodynamics

    PubMed Central

    Li, Junfeng; Zhang, Zhaoyun; Liu, Xiaoxia; Wang, Yi; Mao, Fei; Mao, Junjun; Lu, Xiaolan; Jiang, Dongdong; Wan, Yun; Lv, Jia-Ying; Cao, Guoying; Zhang, Jing; Zhao, Naiqing; Atkinson, Mark; Greiner, Dale L.; Prud'homme, Gerald J.; Jiao, Zheng; Li, Yiming; Wang, Qinghua

    2015-01-01

    Preclinical studies show that GABA exerts anti-diabetic effects in rodent models of type 1 diabetes. Because little is known about its absorption and effects in humans, we investigated the pharmacokinetics and pharmacodynamics of GABA in healthy volunteers. Twelve subjects were subjected to an open-labeled, three-period trial involving sequential oral administration of placebo, 2 g GABA once, and 2 g GABA three times/day for 7 days, with a 7-day washout between each period. GABA was rapidly absorbed (Tmax: 0.5 ~ 1 h) with the half-life (t1/2) of 5 h. No accumulation was observed after repeated oral GABA administration for 7 days. Remarkably, GABA significantly increased circulating insulin levels in the subjects under either fasting (1.6-fold, single dose; 2.0-fold, repeated dose; p < 0.01) or fed conditions (1.4-fold, single dose; 1.6-fold, repeated dose; p < 0.01). GABA also increased glucagon levels only under fasting conditions (1.3-fold, single dose, p < 0.05; 1.5-fold, repeated dose, p < 0.01). However, there were no significant differences in the insulin-to-glucagon ratio and no significant change in glucose levels in these healthy subjects during the study period. Importantly, GABA significantly decreased glycated albumin levels in the repeated dosing period. Subjects with repeated dosing showed an elevated incidence of minor adverse events in comparison to placebo or the single dosing period, most notably transient discomforts such as dizziness and sore throat. However, there were no serious adverse events observed throughout the study. Our data show that GABA is rapidly absorbed and tolerated in human beings; its endocrine effects, exemplified by increasing islet hormonal secretion, suggest potential therapeutic benefits for diabetes. PMID:26617516

  15. Antitussive effects of nasal thymol challenges in healthy volunteers.

    PubMed

    Gavliakova, S; Biringerova, Z; Buday, T; Brozmanova, M; Calkovsky, V; Poliacek, I; Plevkova, J

    2013-06-01

    Eighteen healthy volunteers with normal lung function were tested for cough. Before and after nasal administration of thymol (0.025 ml, 10(-3) M) into both nostrils, urge-to-cough, cough threshold, cumulative and total count of coughs per provocation were estimated during standardized and validated capsaicin cough challenge. Nasal thymol challenges induced pleasant olfactory sensation and in 6 out of the 18 subjects also mild cooling sensation. Cough threshold was not influenced when compared with intranasal saline and vehicle challenges (12.5 vs. 13.2 vs. 10.2 μM of capsaicin to induce two or more coughs (C2), respectively), but the total count of coughs after nasal thymol challenge was significantly lower than that obtained after saline or vehicle (19 vs. 20 vs. 14 coughs/provocation, respectively; p<0.05). Importantly, subjects did not report the urge to cough, which appeared to correspond to C2. We conclude that the modulation of cough by thymol is mostly of olfactory origin.

  16. [Meteoadaptogenic properties of peptide drugs in healthy volunteers].

    PubMed

    Shabanov, P D; Ganapol'skiĭ, V P; Aleksandrov, P V

    2007-01-01

    The meteoadaptogenic properties of a series of drugs with peptide (cortexin, noopept, dilept) and nonpeptide (vinpotropil) structure were investigated in a climate thermobarocomplex (Tabay, Japan) on a group of healthy volunteers aged 20-24. All the studied drugs produced a meteoadaptogenic action, the extent of which depended on the environmental test conditions (overcooling, overheating, hypobaric hypoxia). Vinpotropil, optimizing a physiological component of the functional state, can be recommended as a meteoadaptogen for both cold and hot climate as well as for hypobaric hypoxia, where it improved the psychological component of the functional state. Cortexin is qualified as an adaptogen and actoprotector only for hypobaric hypoxia conditions (uplands). Noopept, affecting positively a psychological component of the functional state, can be used for rapid adaptation to both cold and hot climate. In the hot climate, noopept also enhanced the physical work capacity. Dilept mostly elevated the psychological component of the functional state and can be considered as a psychomotor enhancer and adaptogen. Therefore, all the drugs studied (vinpotropil, cortexin, noopept and dilept) can be recommended as the agents producing activation, support and recovery of the physical and psychological efficiency under rapidly changing environment conditions. PMID:18318195

  17. Hemodynamic characteristics of midazolam, propofol, and dexmedetomidine in healthy volunteers

    PubMed Central

    Frölich, Michael A.; Arabshahi, Ali; Katholi, Charles; Prasain, Jeevan; Barnes, Stephen

    2013-01-01

    Study Objective To study the effect of intravenous (IV) sedation on blood pressure (BP), heart rate (HR), and respiratory rates (RR) to determine if IV sedatives differ with respect to their effect on BP, HR, and RR. Design Prospective, randomized, single-blinded, placebo-controlled study. Setting Monitored patient care room at a clinical research center. Subjects 60 healthy ASA physical status 1 volunteers. Interventions Subjects were randomized to receive, in increasing doses, one of three IV sedatives: propofol, midazolam, or dexmedetomidine; or saline control. Measurements Blood pressure (systolic, diastolic), HR, and RR were recorded. Main Results A significant dose-dependent BP reduction occurred with dexmedetomidine and, to a lesser degree, with propofol; and there was good agreement of predicted versus measured drug concentrations for all sedatives. Blood pressure and HR of participants who received midazolam did not change. Conclusions When administered in sedative doses, dexmedetomidine and, to a lesser extent, midazolam, reduces BP in a dose-dependent fashion. Dexmedetomidine also reduces HR. Midazolam does not affect BP or HR. PMID:21570617

  18. Bioequivalence Study of Donepezil Hydrochloride Tablets in Healthy Male Volunteers

    PubMed Central

    Rojanasthien, Noppamas; Aunmuang, Siriluk; Hanprasertpong, Nutthiya; Roongapinun, Sukit; Teekachunhatean, Supanimit

    2012-01-01

    The objective of this study was to investigate the bioequivalence of two formulations of 5 mg donepezil HCL tablets: Tonizep as the test and Aricept as the reference. The two products were administered as a single oral dose according to a randomized two-phase crossover with a 3-week washout period in 20 healthy Thai Male volunteers. After drug administration, serial blood samples were collected over a period of 216 hours. Plasma donepezil concentrations were measured by high performance liquid chromatography with UV detection. Pharmacokinetic parameters were analyzed based on noncompartmental analysis. The logarithmically transformed data of AUC0–∞ and Cmax were analyzed for 90% confidence intervals (CI) using ANOVA. The mean (90% CI) values for the ratio of AUC0–∞ and Cmax values of the test product over those of the reference product were 1.08 (1.02–1.14) and 1.08 (0.99–1.17), respectively (within the bioequivalence range of 0.8–1.25). The median Tmax for the test product was similar to that of the reference product (2.0 hr), and the 90% CI for the Tmax difference between the two preparations was –0.19 to 0.29 hr and within the bioequivalence range of ± 20% of the Tmax of the reference formulation. Our study demonstrated the bioequivalence of the two preparations. PMID:23209934

  19. Sensorimotor function of the cervical spine in healthy volunteers

    PubMed Central

    Artz, Neil J.; Adams, Michael A.; Dolan, Patricia

    2015-01-01

    Background Sensorimotor mechanisms are important for controlling head motion. However, relatively little is known about sensorimotor function in the cervical spine. This study investigated how age, gender and variations in the test conditions affect measures of position sense, movement sense and reflex activation in cervical muscles. Methods Forty healthy volunteers (19M/21F, aged 19–59 years) participated. Position sense was assessed by determining repositioning errors in upright and flexed neck postures during tests performed in 25%, 50% and 75% cervical flexion. Movement sense was assessed by detecting thresholds to passive flexion and extension at velocities between 1 and 25°s− 1. Reflexes were assessed by determining the latency and amplitude of reflex activation in trapezius and sternocleidomastoid muscles. Reliability was evaluated from intraclass correlation coefficients. Findings Mean repositioning errors ranged from 1.5° to 2.6°, were greater in flexed than upright postures (P = 0.006) and in people aged over 25 years (P = 0.05). Time to detect head motion decreased with increasing velocity (P < 0.001) and was lower during flexion than extension movements (P = 0.002). Reflexes demonstrated shorter latency (P < 0.001) and greater amplitude (P = 0.009) in trapezius compared to sternocleidomastoid, and became slower and weaker with age. None of the measures were influenced by gender. Reliability was good for movement sense measures, but was influenced by the test conditions when assessing position sense. Interpretation Increased repositioning errors and slower reflexes in older subjects suggest that sensorimotor function in the cervical spine becomes impaired with age. In position sense tests, reliability was influenced by the test conditions with mid-range flexion movements, performed in standing, providing the most reliable measurements. PMID:25686675

  20. Moderate red wine consumption improves hemorheological parameters in healthy volunteers.

    PubMed

    Toth, A; Sandor, B; Papp, J; Rabai, M; Botor, D; Horvath, Zs; Kenyeres, P; Juricskay, I; Toth, K; Czopf, L

    2014-01-01

    Pieces of epidemiological evidence have supported that moderate red wine consumption reduces the risk of cardiovascular diseases (French-paradox). Our previous in vitro experiment has demonstrated favourable hemorheological effects of red wine, alcohol-free red wine extract and ethanol. Thirty-nine healthy, non-smoking male volunteers between 18-40 years were assigned into two groups: control group had drunk water, while red wine group had consumed 2 dl of red wine each day at dinner for 3 weeks. No alcohol had been drunk for one week prior to the study. Blood was obtained in the morning of the first and last day. Hematocrit (Hct), plasma (PV) and whole blood viscosity (WBV) (Hevimet 40 capillary viscometer), red blood cell (RBC) aggregation (Myrenne and LORCA aggregometer) and deformability (LORCA ektacytometer) were measured and Hct/WBV ratio was calculated to determine oxygen carrying capacity. Hct was adjusted to 40%. Hct and PV were not affected. WBV remained unchanged in controls, but it considerably decreased in the red wine group compared to the 3-week control group, while Hct/WBV ratio became significantly higher in the red wine group compared to the control (p < 0.05). RBC aggregation significantly decreased in the red wine group and became significantly lower compared to the 3-week controls (p < 0.05). Red wine significantly increased RBC deformability (p < 0.05) at high shear stress. Our results show that moderate red wine consumption has beneficial effects on hemorheological parameters which may contribute to the French-paradox.

  1. Validation of the Beliefs against Volunteering Scale among Chinese Adolescents in Hong Kong

    ERIC Educational Resources Information Center

    Law, Ben M. F.; Shek, Daniel T. L.

    2011-01-01

    Participation in volunteer service is an indicator of quality of life. This study attempts to validate the Beliefs Against Volunteering Scale (BAV), an assessment of the negative beliefs about volunteerism among Chinese adolescents in Hong Kong. The BAV was administered to 5,946 Chinese adolescents. The BAV and its subscales were found to be…

  2. Exposure to wood smoke particles produces an inflammation in healthy volunteers

    EPA Science Inventory

    Background. Human exposure to wood smoke particles (WSP) is of consequence in indoor air quality, exposures from wild fires, burning ofbiomass, and air pollution. This investigation tested the postulate that healthy volunteers exposed to WSP would demonstrate pulmonary and cardio...

  3. Accumulation of caffeine in healthy volunteers treated with furafylline.

    PubMed Central

    Tarrus, E; Cami, J; Roberts, D J; Spickett, R G; Celdran, E; Segura, J

    1987-01-01

    The pharmacokinetics and tolerance of repeated oral doses of furafylline were investigated in normal volunteers. In accord with predictions from single dose studies, steady state was achieved on the first day following the administration of 90 mg and maintained by subsequent daily doses of 30 mg. When corrected for body weight there were no significant differences in minimum and maximum plateau levels of furafylline between males (1.2-2.0 micrograms ml-1; mean body weight 67.2 kg) and females (1.6-2.6 micrograms ml-1; mean body weight 54.9 kg). The half-life of elimination was less when the plasma concentration was lower than 600 ng ml-1 than during the stationary phase of treatment. Despite constant plasma levels the repeated administration of furafylline appeared to be associated with the onset of adverse xanthine-like side effects, a finding which was subsequently traced to the presence of, and possible synergism with, accumulating serum levels of caffeine in those volunteers drinking caffeine containing beverages. Subsequent studies showed that a single dose (90 mg) of furafylline results in a rapid accumulation of caffeine given orally (100 mg twice daily) and that this is accompanied by an elimination half-life of some 50 h and an abrupt decrease in metabolite levels. The furafylline-induced accumulation of caffeine was not influenced by the smoking habits of the subjects, implying that the metabolite pathway blocked by furafylline is the demethylation of caffeine in position 3, an implication confirmed by the reduced formation of paraxanthine. This demonstration of an unacceptable level of adverse side effects resulting from a potent inhibiting effect of furafylline on the metabolism of a normal dietary constituent has obvious implications in the interpretation of drug-induced toxicity. PMID:3814465

  4. Association between common CYP1A2 polymorphisms and theophylline metabolism in non-smoking healthy volunteers.

    PubMed

    Wang, Liqing; Hu, Zheyi; Deng, Xun; Wang, Yong; Zhang, Zhongyi; Cheng, Ze-Neng

    2013-04-01

    This study was designed to investigate the impact of cytochrome P450 (CYP) 1A2 polymorphisms on theophylline metabolism in a non-smoking healthy male Chinese population. Four polymorphisms CYP1A2 1C (G-3860A), G-3113A, CYP1A2 1F (C-163A) and CYP1A2 1B (C-5347T) were screened in 238 unrelated male volunteers. Then, a single oral 200-mg dose of theophylline was administered to 37 volunteers, who were selected from 238 volunteers based on the CYP1A2 genotype. CYP1A2 activities were evaluated by plasma 1,7-dimethylxanthine/caffeine ratios (17X/137X) after administration of 100-mg caffeine. The plasma concentrations of theophylline, 17X and 137X were determined by high-performance liquid chromatography. The activity of CYP1A2 was lower in volunteers with the -3113 AA genotype compared with those with the -3113 AG genotype (0.35 ± 0.04 versus 0.48 ± 0.07, p = 0.016) or the -3113 GG genotype (0.35 ± 0.04 versus 0.58 ± 0.22, p = 0.037). CYP1A2 1F polymorphisms were associated with increased CYP1A2 activity in volunteers with -3860G/-3113G/5347C homozygosity (0.66 ± 0.24 versus 0.46 ± 0.05, p = 0.034). However, theophylline metabolism showed no difference among volunteers carrying different haplotype pairs. CYP1A2 genetic polymorphisms influenced CYP1A2 enzyme activity as measured by caffeine, but CYP1A2 gene polymorphisms appeared to have limited influence on theophylline metabolism in our study.

  5. Using "clinical trial diaries" to track patterns of participation for serial healthy volunteers in U.S. phase I studies.

    PubMed

    Edelblute, Heather B; Fisher, Jill A

    2015-02-01

    Phase I testing of investigational drugs relies on healthy volunteers as research participants. Many U.S. healthy volunteers enroll repeatedly in clinical trials for the financial compensation. Serial participants are incentivized to ignore restrictions on their participation, and no centralized clinical trial registry prevents dual enrollment. Little is currently known about how healthy volunteers participate in studies over time, hampering the development of policies to protect this group. We detail a methodology developed as part of a longitudinal study to track in real-time healthy volunteers' Phase I participation. Illustrating these data through three case studies, we document how healthy volunteers use strategies, such as qualifying for studies at more than one clinic and traveling significant distances, to maximize their participation. Our findings suggest that "clinical trial diaries" can generate critical information about serial research participation and point to ethical issues unique to healthy volunteers' involvement in Phase I clinical trials. PMID:25742668

  6. Using "clinical trial diaries" to track patterns of participation for serial healthy volunteers in U.S. phase I studies.

    PubMed

    Edelblute, Heather B; Fisher, Jill A

    2015-02-01

    Phase I testing of investigational drugs relies on healthy volunteers as research participants. Many U.S. healthy volunteers enroll repeatedly in clinical trials for the financial compensation. Serial participants are incentivized to ignore restrictions on their participation, and no centralized clinical trial registry prevents dual enrollment. Little is currently known about how healthy volunteers participate in studies over time, hampering the development of policies to protect this group. We detail a methodology developed as part of a longitudinal study to track in real-time healthy volunteers' Phase I participation. Illustrating these data through three case studies, we document how healthy volunteers use strategies, such as qualifying for studies at more than one clinic and traveling significant distances, to maximize their participation. Our findings suggest that "clinical trial diaries" can generate critical information about serial research participation and point to ethical issues unique to healthy volunteers' involvement in Phase I clinical trials.

  7. Recruiting Healthy Volunteers for Research Participation via Internet Advertising

    PubMed Central

    Bramstedt, Katrina A.

    2007-01-01

    Objective: The Internet is frequently used as a tool to recruit research subjects, and the US Food and Drug Administration (FDA) provides general guidance regarding such advertising. The goal of this study was to explore the incidence and nature of ethically inappropriate recruiting advertisements on the Internet and to provide descriptive guidance to researchers for responsible Internet recruiting. Methods: In this study, 119 advertisements recruiting health volunteers and listed on the CenterWatch Clinical Trials Listing Service website were reviewed for content as well as text style and visual effects. Results: The majority of advertisements satisfied FDA guidance. However, 21 (18%) were ethically troubling with regard to font size, font style, and/or verbiage. In many advertisements, it was unclear if “medication” meant “investigational drug,” “over-the-counter medication” or US FDA approved “prescription medication.” Nearly 30% of the 119 advertisements used the terms “free,” “no charge” or “no cost” as lures. Conclusion: Ethically problematic recruiting advertisements can be coercive and misleading. Descriptive guidance provided in this paper can help clinical researchers create ethically appropriate recruiting advertisements. PMID:17607043

  8. Increased Set Shifting Costs in Fasted Healthy Volunteers

    PubMed Central

    Bolton, Heather M.; Burgess, Paul W.; Gilbert, Sam J.; Serpell, Lucy

    2014-01-01

    We investigated the impact of temporary food restriction on a set shifting task requiring participants to judge clusters of pictures against a frequently changing rule. 60 healthy female participants underwent two testing sessions: once after fasting for 16 hours and once in a satiated state. Participants also completed a battery of questionnaires (Hospital Anxiety and Depression Scale [HADS]; Persistence, Perseveration and Perfectionism Questionnaire [PPPQ-22]; and Eating Disorders Examination Questionnaire [EDE-Q6]). Set shifting costs were significantly increased after fasting; this effect was independent of self-reported mood and perseveration. Furthermore, higher levels of weight concern predicted a general performance decrement under conditions of fasting. We conclude that relatively short periods of fasting can lead to set shifting impairments. This finding may have relevance to studies of development, individual differences, and the interpretation of psychometric tests. It also could have implications for understanding the etiology and maintenance of eating disorders, in which impaired set shifting has been implicated. PMID:25025179

  9. Early effects of duloxetine on emotion recognition in healthy volunteers.

    PubMed

    Bamford, Susan; Penton-Voak, Ian; Pinkney, Verity; Baldwin, David S; Munafò, Marcus R; Garner, Matthew

    2015-05-01

    The serotonin-noradrenaline reuptake inhibitor (SNRI) duloxetine is an effective treatment for major depression and generalised anxiety disorder. Neuropsychological models of antidepressant drug action suggest therapeutic effects might be mediated by the early correction of maladaptive biases in emotion processing, including the recognition of emotional expressions. Sub-chronic administration of duloxetine (for two weeks) produces adaptive changes in neural circuitry implicated in emotion processing; however, its effects on emotional expression recognition are unknown. Forty healthy participants were randomised to receive either 14 days of duloxetine (60 mg/day, titrated from 30 mg after three days) or matched placebo (with sham titration) in a double-blind, between-groups, repeated-measures design. On day 0 and day 14 participants completed a computerised emotional expression recognition task that measured sensitivity to the six primary emotions. Thirty-eight participants (19 per group) completed their course of tablets and were included in the analysis. Results provide evidence that duloxetine, compared to placebo, may reduce the accurate recognition of sadness. Drug effects were driven by changes in participants' ability to correctly detect subtle expressions of sadness, with greater change observed in the placebo relative to the duloxetine group. These effects occurred in the absence of changes in mood. Our preliminary findings require replication, but complement recent evidence that sadness recognition is a therapeutic target in major depression, and a mechanism through which SNRIs could resolve negative biases in emotion processing to achieve therapeutic effects. PMID:25759400

  10. Early effects of duloxetine on emotion recognition in healthy volunteers.

    PubMed

    Bamford, Susan; Penton-Voak, Ian; Pinkney, Verity; Baldwin, David S; Munafò, Marcus R; Garner, Matthew

    2015-05-01

    The serotonin-noradrenaline reuptake inhibitor (SNRI) duloxetine is an effective treatment for major depression and generalised anxiety disorder. Neuropsychological models of antidepressant drug action suggest therapeutic effects might be mediated by the early correction of maladaptive biases in emotion processing, including the recognition of emotional expressions. Sub-chronic administration of duloxetine (for two weeks) produces adaptive changes in neural circuitry implicated in emotion processing; however, its effects on emotional expression recognition are unknown. Forty healthy participants were randomised to receive either 14 days of duloxetine (60 mg/day, titrated from 30 mg after three days) or matched placebo (with sham titration) in a double-blind, between-groups, repeated-measures design. On day 0 and day 14 participants completed a computerised emotional expression recognition task that measured sensitivity to the six primary emotions. Thirty-eight participants (19 per group) completed their course of tablets and were included in the analysis. Results provide evidence that duloxetine, compared to placebo, may reduce the accurate recognition of sadness. Drug effects were driven by changes in participants' ability to correctly detect subtle expressions of sadness, with greater change observed in the placebo relative to the duloxetine group. These effects occurred in the absence of changes in mood. Our preliminary findings require replication, but complement recent evidence that sadness recognition is a therapeutic target in major depression, and a mechanism through which SNRIs could resolve negative biases in emotion processing to achieve therapeutic effects.

  11. Alexithymia and health behaviors in healthy male volunteers.

    PubMed

    Helmers, K F; Mente, A

    1999-12-01

    The association between alexithymia and maladaptive health behaviors was evaluated in 118 young, healthy men, aged 18-45 years. Subjects completed the Toronto Alexithymia Scale (TAS-26), and a health behaviors questionnaire, measuring alcohol and drug use, sedentary lifestyle, poor nutritional consumption, and risky sexual practices. In forced hierarchical regression analyses, the association between alexithymia and health behaviors was evaluated after adjusting for age, body mass index, social support, ambivalence over expression of emotion, and the expression of emotion. Results indicated that: (1) the TAS-26 and difficulty identifying feelings was associated with poor nutritional consumption; (2) difficulty identifying feelings was associated with greater alcohol and drug use; and (3) difficulty communicating feelings was associated with a more sedentary lifestyle. There was no association between risky sexual practices and alexithymia. These results suggest that, in young men, difficulties with identifying emotions and communicating emotions are associated with maladaptive nutritional habits, a sedentary lifestyle, and substance abuse, even after adjusting for other psychosocial and demographic variables. Such maladaptive health behaviors may help explain the association between alexithymia and premature mortality.

  12. Diesel Exhaust Modulates Ozone-induced Lung Function Decrements in Healthy Human Volunteers

    EPA Science Inventory

    The potential effects of combinations of dilute whole diesel exhaust (DE) and ozone (03), each a common component of ambient airborne pollutant mixtures, on lung function were examined. Healthy young human volunteers were exposed for 2 hr to pollutants while exercising (~50 L/min...

  13. Diclofenac does not interact with codeine metabolism in vivo: A study in healthy volunteers

    PubMed Central

    Ammon, Susanne; Marx, Claudia; Behrens, Christoph; Hofmann, Ute; Mürdter, Thomas; Griese, Ernst-Ulrich; Mikus, Gerd

    2002-01-01

    Background Previously, we have demonstrated a marked inhibition of codeine glucuronidation by diclofenac in human liver tissue homogenate. We therefore aimed to investigate whether diclofenac inhibits glucuronidation of codeine also in vivo in healthy volunteers. Methods In a randomised, placebo-controlled, double-blind, cross-over study, 12 healthy volunteers received a singe of 100 mg codeine phosphate plus 50 mg diclofenac sodium or codeine phosphate plus placebo. Over a 36 hour period serum concentrations of codeine and its metabolites as well as urinary excretion were analysed using LC-mass spectrometry. Side effects were recorded and analgesic efficacy was determined using the cold pressor test (0–6 h). Results A single dose of diclofenac did not alter the formation of codeine-6-glucuronide in healthy volunteers. Metabolic clearance of codeine to morphine was not affected by diclofenac. In terms of side effects, both treatments were well tolerated. Diclofenac did not significantly influence the analgesic effects of codeine in the cold pressor test. Conclusions In contrast to recent in vitro data, a single oral dose of diclofenac did not alter the glucuronidation of codeine in healthy volunteers. PMID:11943073

  14. Family influence on volunteering intention and behavior among Chinese adolescents in Hong Kong.

    PubMed

    Law, Ben M F; Shek, Daniel T L

    2009-01-01

    Based on the responses of 5,946 adolescents (mean age = 14.77), the relationships among family influence, adolescents' volunteering intention, and volunteering behavior in a Chinese context were examined. A 9-item Chinese Family Influence on Adolescent Volunteerism Scale (C-FIAV) was used to measure nine kinds of influence of the family (such as family support) which could be subsumed under two underlying domains (positive family influence and extrinsic family influence). Results showed that family support, family belief, and family modeling were positively associated with both intention and behavior. Family reward and coercion were negatively associated with both intention and behavior. Family belief in volunteerism was the most critical factor. Grade and gender differences were found only in the associations between family influence and volunteering intention. Path models showed that positive and extrinsic family influence had an effect on volunteering behavior directly or via the mediation of volunteering intention. Implications and limitations are discussed. PMID:19950876

  15. The OxyMask™ development and performance in healthy volunteers

    PubMed Central

    Paul, James E; Hangan, Horia; Hajgato, Julius

    2009-01-01

    Background The OxyMask™ is a unique, open-style, oxygen mask that was originally developed in 2005. The original mask was modified, using computational fluid dynamics numerical simulations, with the goal of allowing it to produce a wider range of FiO2. This analysis was used to guide the modification of the mask shell and the location for the oxygen diffuser. Methods The new OxyMask was attached to 10 healthy subjects and used to deliver escalating levels of oxygen (1.5, 2, 2.5, 3, 5, 10, 15, 20, 25 and 30 LPM) for 90 seconds at each level and the resulting FiO2 was recorded (at the lips) from 5 consecutive measurements at each oxygen flow rate. Results Mean FiO2 was 25.4% at 1.5 LPM of oxygen, 30.1% at 2 LPM, 36.5% at 2.5 LPM, 41.8% at 3 LPM, 57.6% at 5 LPM, 74.4% at 10 LPM, and 80.1% at 15 LPM. Each FiO2 achieved at these escalating oxygen levels was significantly greater than all the previous levels. The mean FiO2 was 82.8 at 20 LPM, 84.2% at 25 LPM and 84.3% at 30 LPM. All of these values on average were not significantly greater than the FiO2 achieved with 15 LPM. In a few subjects a maximum FiO2 of 90% was reached. Conclusion The original OxyMask was successfully modified so that the second generation of the mask can provide a wide range of FiO2, from 25% to 90%, while keeping its unique open design. PMID:22915909

  16. Eltrombopag increases plasma rosuvastatin exposure in healthy volunteers

    PubMed Central

    Allred, Alicia J; Bowen, Carolyn J; Park, Jung Wook; Peng, Bin; Williams, Daphne D; Wire, Mary Beth; Lee, Edmund

    2011-01-01

    AIM Eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist, inhibits the organic anion transporting polypeptide 1B1 (OATP1B1) and breast cancer resistance protein (BCRP) in vitro. OATP1B1 is important for hepatic uptake of rosuvastatin and inhibition of this transporter could reduce cholesterol-lowering efficacy and increase the risk of exposure-dependent toxicities. In contrast, BCRP is an efflux transporter and inhibition of this transporter could increase both hepatic and plasma rosuvastatin concentrations, resulting in increased efficacy and toxicity. To determine if co-administration of eltrombopag with rosuvastatin alters plasma rosuvastatin exposure, an open-label study was conducted in 42 healthy adult subjects. METHODS Subjects received rosuvastatin and eltrombopag orally: day 1, rosuvastatin 10 mg single dose; days 6 to 9, eltrombopag 75 mg once daily; day 10, eltrombopag 75 mg once daily and rosuvastatin 10 mg single dose. Adverse event assessments were performed daily and at the follow-up visit. Plasma samples for pharmacokinetic analysis were collected days 1 to 5 and days 10 to 14. RESULTS Co-administration of eltrombopag with rosuvastatin increased geometric mean (90% confidence interval) plasma rosuvastatin AUC(0,∞) by 55% (42%, 69%) and Cmax by 103% (82%, 126%) in the overall study population, with a larger interaction in the non-Asian compared with Asian subjects. CONCLUSIONS Concomitant administration of eltrombopag with rosuvastatin was associated with increased rosuvastatin exposure. The therapeutic index of HMG Co-A reductase inhibitors may be reduced by the concomitant use of eltrombopag. In subjects taking eltrombopag, a reduced dose of HMG Co-A reductase inhibitors may be needed. PMID:21434975

  17. Differences in gluten metabolism among healthy volunteers, coeliac disease patients and first-degree relatives.

    PubMed

    Caminero, Alberto; Nistal, Esther; Herrán, Alexandra R; Pérez-Andrés, Jénifer; Ferrero, Miguel A; Vaquero Ayala, Luis; Vivas, Santiago; Ruiz de Morales, José M G; Albillos, Silvia M; Casqueiro, Francisco Javier

    2015-10-28

    Coeliac disease (CD) is an immune-mediated enteropathy resulting from exposure to gluten in genetically predisposed individuals. Gluten proteins are partially digested by human proteases generating immunogenic peptides that cause inflammation in patients carrying HLA-DQ2 and DQ8 genes. Although intestinal dysbiosis has been associated with patients with CD, bacterial metabolism of gluten has not been studied in depth thus far. The aim of this study was to analyse the metabolic activity of intestinal bacteria associated with gluten intake in healthy individuals, CD patients and first-degree relatives of CD patients. Faecal samples belonging to twenty-two untreated CD patients, twenty treated CD patients, sixteen healthy volunteers on normal diet, eleven healthy volunteers on gluten-free diet (GFD), seventy-one relatives of CD patients on normal diet and sixty-nine relatives on GFD were tested for several proteolytic activities, cultivable bacteria involved in gluten metabolism, SCFA and the amount of gluten in faeces. We detected faecal peptidasic activity against the gluten-derived peptide 33-mer. CD patients showed differences in faecal glutenasic activity (FGA), faecal tryptic activity (FTA), SCFA and faecal gluten content with respect to healthy volunteers. Alterations in specific bacterial groups metabolising gluten such as Clostridium or Lactobacillus were reported in CD patients. Relatives showed similar parameters to CD patients (SCFA) and healthy volunteers (FTA and FGA). Our data support the fact that commensal microbial activity is an important factor in the metabolism of gluten proteins and that this activity is altered in CD patients.

  18. Precursors to suicidality and violence on antidepressants: systematic review of trials in adult healthy volunteers

    PubMed Central

    Bielefeldt, Andreas Ø; Danborg, Pia B

    2016-01-01

    Objective To quantify the risk of suicidality and violence when selective serotonin and serotonin-norepinephrine reuptake inhibitors are given to adult healthy volunteers with no signs of a mental disorder. Design Systematic review and meta-analysis. Main outcome measure Harms related to suicidality, hostility, activation events, psychotic events and mood disturbances. Setting Published trials identified by searching PubMed and Embase and clinical study reports obtained from the European and UK drug regulators. Participants Double-blind, placebo-controlled trials in adult healthy volunteers that reported on suicidality or violence or precursor events to suicidality or violence. Results A total of 5787 publications were screened and 130 trials fulfilled our inclusion criteria. The trials were generally uninformative; 97 trials did not report the randomisation method, 75 trials did not report any discontinuations and 63 trials did not report any adverse events or lack thereof. Eleven of the 130 published trials and two of 29 clinical study reports we received from the regulatory agencies presented data for our meta-analysis. Treatment of adult healthy volunteers with antidepressants doubled their risk of harms related to suicidality and violence, odds ratio 1.85 (95% confidence interval 1.11 to 3.08, p = 0.02, I2 = 18%). The number needed to treat to harm one healthy person was 16 (95% confidence interval 8 to 100; Mantel-Haenszel risk difference 0.06). There can be little doubt that we underestimated the harms of antidepressants, as we only had access to the published articles for 11 of our 13 trials. Conclusions Antidepressants double the occurrence of events in adult healthy volunteers that can lead to suicide and violence. PMID:27729596

  19. Effect of trimethoprim on serum creatinine in healthy and chronic renal failure volunteers.

    PubMed

    Myre, S A; McCann, J; First, M R; Cluxton, R J

    1987-06-01

    The effect of trimethoprim (TMP) on serum creatinine concentration (SCr) was studied in 10 healthy (H) subjects and nine subjects with chronic renal failure (CRF). Each volunteer was given TMP 100 mg perorally every 12 h for 10 days followed by a 7-day washout period. SCr was measured colorimetrically immediately before the study (baseline), on day 10 of TMP, and 7 days after TMP had been discontinued. SCr increased an average of 14.8% from baseline during TMP administration in the H volunteers, but this increase was not statistically significant. During TMP administration to the CRF volunteers, a pronounced elevation (34.6%) of mean SCr from baseline was observed (p less than 0.05). SCr returned to baseline values in both groups following the 7-day washout period. These results are consistent with the hypothesis that TMP competitively inhibits the renal tubular secretion of creatinine. PMID:3617154

  20. Assessing change in health professions volunteers' perceptions after participating in Special Olympics healthy athlete events.

    PubMed

    Freudenthal, Jacqueline J; Boyd, Linda D; Tivis, Rick

    2010-09-01

    This study assessed perceptions of health professions student and faculty volunteers who participated with athletes at the 2009 Special Olympics World Winter Games in Healthy Athlete venues. The volunteers' perceptions and expectations of the abilities of intellectually disabled athletes were measured by administering pre-event and post-event questionnaires consisting of demographic questions and the Prognostic Belief Scale (PBS). Invitations to participate in the study were sent to 165 students and faculty members; of those, eighty (48.5 percent response rate) responded to the pre-event questionnaire, and sixty-seven (40.6 percent response rate) responded to the post-event questionnaire. Of the eighty respondents to the pre-event questionnaire, fifty-five (68.7 percent) also completed the post-event questionnaire. The ANOVA comparing pre- and post-event PBS scores between groups found a trend towards higher scores among the volunteers, but analysis did not demonstrate a significant effect in either group (p=.68) or the interaction of group by time (p=.46). Despite the findings from the PBS, participants' statements suggest the experience had an impact on their perceptions and expectations. Although not statistically significant, this study found a positive trend pre- to post-event in the volunteers' perceptions of the abilities of athletes with intellectual disabilities. In addition to didactic and clinical education, volunteer experiences may enhance care providers' knowledge, skill, and confidence levels for treating clients with intellectual disabilities. PMID:20837738

  1. Effects of low-dose cholecystokinin on respiratory function in healthy volunteers.

    PubMed

    Schruers, K; Caycedo, N; Overbeek, T; Büchold, H; Bourin, M; Griez, E

    2000-09-01

    Injection of high doses of cholecystokinin tetrapeptide (CCK-4), a recent experimental model for panic, causes panic attacks and respiratory stimulation, a key feature of panic, in healthy volunteers. However, it has not yet been established whether respiratory stimulation is specifically linked to panic or merely an effect of arousal in general. Results of the present study show that respiratory stimulation is not merely linked to higher arousal and suggest a link between CCK-provoked panic and respiratory stimulation.

  2. Penetration of Linezolid into Soft Tissues of Healthy Volunteers after Single and Multiple Doses

    PubMed Central

    Dehghanyar, Pejman; Bürger, Cornelia; Zeitlinger, Markus; Islinger, Florian; Kovar, Florian; Müller, Markus; Kloft, Charlotte; Joukhadar, Christian

    2005-01-01

    The present study tested the ability of linezolid to penetrate soft tissues in healthy volunteers. Ten healthy volunteers were subjected to linezolid drug intake at a dose of 600 mg twice a day for 3 to 5 days. The first dose was administered intravenously. All following doses were self-administered orally. The tissue penetration of linezolid was assessed by use of in vivo microdialysis. In the single-dose experiments the ratios of the area under the concentration-time curve from 0 to 8 h (AUC0-8) for tissue to the AUC0-8 for free plasma were 1.4 ± 0.3 (mean ± standard deviation) and 1.3 ± 0.4 for subcutaneous adipose and muscle tissue, respectively. After multiple doses, the corresponding mean ratios were 0.9 ± 0.2 and 1.0 ± 0.5, respectively. The ratios of the AUC from 0 to 24 h (AUC0-24) for free linezolid in tissues to the MIC were between 50 and 100 for target pathogens with MICs between 2 and 4 mg/liter. In conclusion, the present study showed that linezolid penetrates rapidly into the interstitial space fluid of subcutaneous adipose and skeletal muscle tissues in healthy volunteers. On the basis of pharmacokinetic-pharmacodynamic calculations, we suggest that linezolid concentrations in soft tissues can be considered sufficient to inhibit the growth of many clinically relevant bacteria. PMID:15917535

  3. Developing an Older Adult Volunteer Program in a New York Chinese Community: An Evidence-Based Approach.

    PubMed

    Mui, Ada C; Glajchen, Myra; Chen, Huajuan; Sun, Juanjuan

    2013-06-01

    This study reports the results of a pilot volunteer project for older Chinese immigrants and documents benefits for both volunteers and caregiver recipients. Using a social marketing approach, the volunteer project was designed as a social model to promote better health among older Chinese immigrants in New York City. The packaging of this health promotion project as a volunteer program was based on a strengths perspective. In the program, 18 older Chinese immigrants were trained to provide support and referral to family caregivers of ill relatives in the Chinese community. At 6 months, outcomes were evaluated for both volunteers and caregivers. The older volunteers perceived benefits associated with volunteering, specifically, a greater sense of well-being and satisfaction with life. In addition, the majority of volunteers felt empowered by training and volunteering (100 %), felt the skills they learned improved communication with their own families (90 %), and reported physical and emotional health benefits (61 %). At the same time, caregivers reported stress reduction following volunteer support. Findings suggest that a volunteer program model may be an effective health promotion intervention for older Chinese immigrants.

  4. Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha (Withania somnifera) in healthy volunteers.

    PubMed

    Raut, Ashwinikumar A; Rege, Nirmala N; Tadvi, Firoz M; Solanki, Punita V; Kene, Kirti R; Shirolkar, Sudatta G; Pandey, Shefali N; Vaidya, Rama A; Vaidya, Ashok B

    2012-07-01

    Ashwagandha (Withania somnifera) (WS), a "rasayana" drug, is recommended for balavardhan and mamsavardhan. The study was intended to evaluate dose-related tolerability, safety, and activity of WS formulation in normal individuals. The design was prospective, open-labeled, variable doses in volunteers. Eighteen apparently healthy volunteers (12M:6F, age:18-30 years, and BMI: 19-30) were enrolled. After baseline investigations, they received WS capsules (Rx) (aqueous extract, 8:1) daily in two divided doses with increase in daily dosage every 10 days for 30 days (750 mg/day ×10 days, 1 000 mg/day × 10 days, 1 250 mg/day × 10 days). Volunteers were assessed for symptoms/signs, vital functions, hematological and biochemical organ function tests. Muscle activity was measured by hand grip strength, quadriceps strength, and back extensor force. Exercise tolerance was determined using cycle ergometry. Lean body weight and fat% were computed from skin fold thickness measurement. Adverse events were recorded, as volunteered by the subjects. Repeated measures ANOVA, McNemar's test, and paired t test were employed. All but one volunteer tolerated WS without any adverse event. One volunteer showed increased appetite, libido, and hallucinogenic effects with vertigo at the lowest dose and was withdrawn from study. In six subjects, improvement in quality of sleep was found. Organ function tests were in normal range before and after the intervention. Reduction in total- and LDL- cholesterol and increase of strength in muscle activity was significant. Total body fat percentage showed a reduction trend. WS, in escalated dose, was tolerated well. The formulation appeared safe and strengthened muscle activity. In view of its traditional Rasayana use, further studies are planned to evaluate potential of this drug in patients of sarcopenia. PMID:23125505

  5. Immigrants as Active Citizens: Exploring the Volunteering Experience of Chinese Immigrants in Vancouver

    ERIC Educational Resources Information Center

    Guo, Shibao

    2014-01-01

    Despite the fact that immigration has played an important role in transforming Canada into an ethno-culturally diverse and economically prosperous nation, immigrants themselves are often criticised as passive citizens. This study attempts to deconstruct this myth by investigating the volunteering experiences of Chinese immigrants in Vancouver. The…

  6. Cognitive, psychomotor, and subjective effects of sodium oxybate and triazolam in healthy volunteers

    PubMed Central

    Carter, Lawrence P.; Griffiths, Roland R.; Mintzer, Miriam Z.

    2009-01-01

    Rationale Illicit gamma-hydroxybutyrate (GHB) has received attention as a “date rape drug” that produces robust amnesia; however, there is little experimental evidence in support of GHB’s amnestic effects. Objectives This study compared the cognitive effects of GHB (sodium oxybate) with those of triazolam in healthy volunteers. Materials and methods Doses of sodium oxybate (1.125, 2.25, and 4.5 g/70 kg), triazolam (0.125, 0.25, and 0.5 mg/70 kg), and placebo were administered to 15 volunteers under repeated measures, counterbalanced, double-blind, double-dummy conditions. The time course and peak physiological, psychomotor, subjective, and cognitive effects were examined. Results Sodium oxybate and triazolam produced similar increases in participant ratings of drug effects. Performance on psychomotor, working memory, and episodic memory tasks was impaired to a greater extent after triazolam than sodium oxybate. Conclusions Together, these data suggest that sodium oxybate produces less psychomotor and cognitive impairment than triazolam at doses that produce equivalent participant-rated subjective effects in healthy volunteers. PMID:19543883

  7. Sufentanil does not increase cerebral blood flow in healthy human volunteers

    SciTech Connect

    Mayer, N.; Weinstabl, C.; Podreka, I.; Spiss, C.K. )

    1990-08-01

    The effect of sufentanil on human cerebral blood flow (CBF) was studied in seven unpremedicated, healthy volunteers 31 +/- 3.5 yr of age (mean +/- SD) and either sex. CBF (ml.100 g-1.min-1) was measured noninvasively with the 133Xe clearance technique and a scintillation camera before and after sufentanil 0.5 micrograms/kg administered intravenously. This technique provides values for global blood flow and for gray and white matter blood flow, and from 13 preselected regions in one hemisphere. After the administration of sufentanil, the volunteers were stimulated verbally in order to prevent their loss of consciousness and hypercarbia. Heart rate (HR), arterial pressure, oxyhemoglobin saturation, and end-tidal CO2 ETCO2 were recorded during the measurements. Neither global CBF (46.1 +/- 1.6 control and 43 +/- 1.9 after sufentanil, mean +/- SEM) nor gray (76.5 +/- 3.2 and 70.9 +/- 6.1) or white (22.7 +/- 1.5 and 24.2 +/- 1.6) matter blood flow changed significantly after sufentanil administration. As well, no significant differences in HR (72 +/- 4 control and 79 +/- 4 beats per min after sufentanil) and ETCO2 (39.8 +/- 1.4 and 41.1 +/- 1.1 mmHg) were observed. It is concluded that sufentanil has no significant effect on CBF in healthy human volunteers.

  8. Effects of clear liquids on gastric volume and pH in healthy volunteers.

    PubMed

    Shevde, K; Trivedi, N; Gross, M

    1991-04-01

    The effects of clear liquids on gastric volume and pH were examined in 30 healthy ASA physical status I volunteers. After overnight fasting, a Salem-sump nasogastric tube was inserted and gastric contents were removed for measurement of volume and pH. Gastric contents were then reinserted through the nasogastric tube into the stomach. The volunteers were randomly divided into three groups: group 1 (n = 10) received 240 mL water, group 2 (n = 10) received 240 mL coffee, and group 3 (n = 10) received 240 mL pulp-free orange juice. All liquids were administered orally. Gastric contents were then again aspirated, measured for volume and pH, and reinserted through the nasogastric tube every half hour until gastric volume was less than 25 mL. All volunteers had gastric volumes less than 25 mL with a slight decrease in pH within 2 h of orally taking one of the three 240-mL liquids. These data suggest that if patients have ingested a moderate amount of clear liquids it is safe to conduct general anesthesia after a 2-h fast in healthy surgical patients.

  9. Feeding and Bleeding: The Institutional Banalization of Risk to Healthy Volunteers in Phase I Pharmaceutical Clinical Trials

    PubMed Central

    Fisher, Jill A.

    2015-01-01

    Phase I clinical trials are the first stage of testing new pharmaceuticals in humans. The majority of these studies are conducted under controlled, inpatient conditions using healthy volunteers who are paid for their participation. This article draws on an ethnographic study of six phase I clinics in the United States, including 268 semistructured interviews with research staff and healthy volunteers. In it, I argue that an institutional banalization of risk structures the perceptions of research staff and healthy volunteers participating in the studies. For research staff, there are three mechanisms by which risk becomes banal: a perceived homogeneity of studies, Fordist work regimes, and data-centric discourse. For healthy volunteers, repeat study participation contributes to the institutional banalization of risk both through the process of desensitization to risk and the formation of trust in the clinics. I argue that the institutional banalization of risk also renders invisible ethical concerns about exploitation of underprivileged groups in pharmaceutical research. PMID:25914430

  10. New Combined Parameter of Liver and Splenic Stiffness as Determined by Elastography in Healthy Volunteers

    PubMed Central

    Kassym, Laura; Nounou, Mohammed A.; Zhumadilova, Zauresh; Dajani, Asad I.; Barkibayeva, Nurgul; Myssayev, Ayan; Rakhypbekov, Tolebay; Abuhammour, Adnan M.

    2016-01-01

    Background: The diagnosis of chronic liver disease (CLD) leading to fibrosis, cirrhosis, and portal hypertension had witnessed dramatic changes after the introduction of noninvasive figure accessible tools over the past few years. Imaging techniques that are based on evaluation of the liver stiffness was particularly useful in this respect. Acoustic radiation force impulse (ARFI) emerged as an interesting figure tool with reliable repute and high precision. Aims: To evaluate liver stiffness measurement (LSM) and splenic stiffness measurement (SSM) in healthy volunteers as concluded by the ARFI technique and to out a numeric calculated ratio that may reflect their correlation in the otherwise healthy liver. Patients and Methods: A ratio (splenic stiffness/liver stiffness in kPa) was determined in 207 consenting healthy subjects and was investigated with respect to age, gender, ethnic origin, body mass index (BMI), liver and spleen sizes healthy volunteers, alanine aminotransferase (ALT), aspartate aminotransferase (AST), platelet count (PLT), APRI, and FIB-4 scores. Results: Data from this work led to computing an index of 4.72 (3.42–7.33) in healthy persons on an average. Females had a higher index than males 6.37 vs 4.92, P=0.002. There was not any significant difference of the ratio in different age groups; ethnic origins; any correlation between SSM/LSM ratio and BMI; liver and spleen sizes; or ALT, AST, PLT, APRI, and FIB-4 scores. Conclusions: A quantifiable numeric relationship between splenic and liver stiffness in the healthy subjects could be computed to a parameter expressed as SSM/LSM ratio. We believe that this ratio can be a useful reference tool for further researches in CLD. PMID:27488328

  11. Subacromial space in adult patients with thoracic hyperkyphosis and in healthy volunteers.

    PubMed

    Gumina, Stefano; Di Giorgio, Giantony; Postacchini, Franco; Postacchini, Roberto

    2008-02-01

    The assumption that subacromial space decreases in patients with thoracic hyperkyphosis arises from sporadic and personal observations. The purpose of this study was to compare width of subacromial space calculated on radiographs and CT scans of a high number of patients with thoracic hyperkyphosis that registered on exams of healthy volunteers. We measured the subacromial space, using Petersson's method, on radiographs of 47 patients with idiopathic or acquired thoracic hyperkyphosis and of 175 healthy shoulder volunteers. Both groups were further distinguished considering gender and age. Females with hyperkyphosis were also divided in two subgroups: those with a kyphotic curve of less (24 patients) or more (19 patients) than 50 degrees , respectively. Subacromial space of all patients and of 21 volunteers was also evaluated using CT. Acromio-humeral space was less wide in patients with hyperkyphosis with respect to coeval volunteers of the same gender; in females and in subjects older than 60. Subacromial width of females with hyperkyphosis whose curve was more than 50 degrees was significantly narrower (p<0.05) than that measured on radiograms or CT scans of females with a less severe spinal deformity. Decrease of subacromial space may be attributed to less posterior tilting of the scapula and to dyskinesis of the scapular movement. Scapular malposition causes an anomalous orientation of the acromion that may contribute to subacromial impingement. Patients with thoracic hyperkyphosis greater than 50 degrees had a subacromial space narrower than that measured in patients with a less severe kyphosis. This suggests that subacromial width is directly related to severity of thoracic kyphosis. Because hyperkyphosis of patients with osteoporotic vertebral fractures may worsen over the time, subacromial decompression could give only temporary shoulder pain relief. PMID:18320381

  12. Albendazole-praziquantel interaction in healthy volunteers: kinetic disposition, metabolism and enantioselectivity

    PubMed Central

    Lima, Renata Monteiro; Ferreira, Maria Augusta Drago; de Jesus Ponte Carvalho, Teresa Maria; Dumêt Fernandes, Bruno José; Takayanagui, Osvaldo Massaiti; Garcia, Hector Hugo; Coelho, Eduardo Barbosa; Lanchote, Vera Lucia

    2011-01-01

    AIM This study investigated the kinetic disposition, metabolism and enantioselectivity of albendazole (ABZ) and praziquantel (PZQ) administered alone and in combination to healthy volunteers. METHODS A randomized crossover study was carried out in three phases (n = 9), in which some volunteers started in phase 1 (400 mg ABZ), others in phase 2 (1500 mg PZQ), and the remaining volunteers in phase 3 (400 mg ABZ + 1500 mg PZQ). Serial blood samples were collected from 0–48 h after drug administration. Pharmacokinetic parameters were calculated using a monocompartmental model with lag time and were analyzed using the Wilcoxon test; P≤ 0.05. RESULTS The administration of PZQ increased the plasma concentrations of (+)-ASOX (albendazole sulphoxide) by 264% (AUC 0.99 vs. 2.59 µg ml−1 h), (−)-ASOX by 358% (0.14 vs. 0.50 µg ml−1 h) and albendazole sulfone (ASON) by 187% (0.17 vs. 0.32 µg ml−1 h). The administration of ABZ did not change the kinetic disposition of (+)-(S)-PZQ (–)-(R)-4-OHPZQ or (+)-(S)-4-OHPZQ, but increased the plasma concentration of (–)-(R)-PZQ by 64.77% (AUC 0.52 vs. 0.86 µg ml−1 h). CONCLUSIONS The pharmacokinetic interaction between ABZ and PZQ in healthy volunteers was demonstrated by the observation of increased plasma concentrations of ASON, both ASOX enantiomers and (–)-(R)-PZQ. Clinically, the combination of ABZ and PZQ may improve the therapeutic efficacy as a consequence of higher concentration of both active drugs. On the other hand, the magnitude of this elevation may represent an increased risk of side effects, requiring, certainly, reduction of the dosage. However, further studies are necessary to evaluate the efficacy and safety of this combination. PMID:21395645

  13. A single consumption of high amounts of the Brazil nuts improves lipid profile of healthy volunteers.

    PubMed

    Colpo, Elisângela; Vilanova, Carlos Dalton de Avila; Brenner Reetz, Luiz Gustavo; Medeiros Frescura Duarte, Marta Maria; Farias, Iria Luiza Gomes; Irineu Muller, Edson; Muller, Aline Lima Hermes; Moraes Flores, Erico Marlon; Wagner, Roger; da Rocha, João Batista Teixeira

    2013-01-01

    Background. This study investigates the effects of Brazil nut ingestion on serum lipid profile in healthy volunteers. Methods. Ten healthy subjects were enrolled in the study. Each subject was tested 4 times in a randomized crossover in relation to the ingestion of different serving sizes of the Brazil nut: 0, 5, 20, or 50 g. At each treatment point, peripheral blood was drawn before and at 1, 3, 6, 9, 24, and 48 hours and 5 and 30 days. Blood samples were tested for total cholesterol, high- and low-density lipoprotein cholesterol (HDL-c and LDL-c, resp.), triglycerides, selenium, aspartate and alanine aminotransferases, albumin, total protein, alkaline phosphatase, gamma GT, urea, creatinine, and C-reactive protein. Results. A significant increase of the plasma selenium levels was observed at 6 hours within the groups receiving the nuts. Serum LDL-c was significantly lower, whereas HDL-c was significantly higher 9 hours after the ingestion of 20 or 50 g of nuts. The biochemical parameters of liver and kidney function were not modified by ingestion of nuts. Conclusions. This study shows that the ingestion of a single serving of Brazil nut can acutely improve the serum lipid profile of healthy volunteers.

  14. Pharmacokinetics of the antiepileptic drug levetiracetam in healthy Japanese and Caucasian volunteers following intravenous administration.

    PubMed

    Toublanc, Nathalie; Okagaki, Takuya; Boyce, Malcolm; Chan, Robert; Mugitani, Ayumi; Watanabe, Shikiko; Yamamoto, Katsumi; Yoshida, Katsumi; Andreas, Jens-Otto

    2015-12-01

    The intravenous (iv) formulation of levetiracetam has been available in clinical practice worldwide for several years, but not in Japan. Two open-label studies were conducted: Study A evaluated the bioequivalence of iv and oral tablet formulations in healthy Japanese volunteers; and Study B subsequently compared the pharmacokinetics of iv levetiracetam in healthy Japanese and Caucasian volunteers. Study A had a randomised, two-way crossover design; a single 1,500 mg levetiracetam dose was administered as a 15-min iv infusion and as 3 × 500 mg oral tablets to Japanese volunteers. In Study B, 1,500 mg levetiracetam was administered as single and repeated 15-min iv infusions to Japanese and Caucasian volunteers. Overall, 26/27 volunteers completed Study A and 32/32 (16 Japanese; 16 Caucasian) completed Study B. In Study A, the point estimate and 90 % confidence interval (CI) for the geometric least squares mean (LSM) ratio (iv vs oral) were fully included within the acceptance range for bioequivalence (0.85-1.25) for the area under plasma concentration-time curve from 0 to last quantifiable observation (AUClast 0.97 [0.95, 0.99]), but not for the maximum plasma concentration (C max 1.64 [1.47, 1.83]). In Study B, after a single iv infusion, the point estimates (90 % CI) for the geometric LSM ratio (Japanese vs Caucasian) for body weight-normalised C max and AUClast were 1.21 (1.07, 1.36) and 0.97 (0.90, 1.04), respectively. Corresponding values after repeated iv infusions were C max,ss 1.01 (0.91, 1.12) and AUCτ,ss 0.89 (0.83, 0.96). Levetiracetam was well tolerated in both studies. Study A did not demonstrate the bioequivalence of single doses of levetiracetam 1,500 mg administered as an iv infusion and as oral tablets in healthy Japanese adults. Study B, however, showed that pharmacokinetic profiles were generally similar between Japanese and Caucasian adults after single and repeated iv infusions of levetiracetam 1,500 mg.

  15. Effect of ABCB1 polymorphisms and atorvastatin on sitagliptin pharmacokinetics in healthy volunteers

    PubMed Central

    Aquilante, Christina L.; Wempe, Michael F.; Sidhom, Maha S.; Kosmiski, Lisa A.; Predhomme, Julie A.

    2013-01-01

    Objectives The objectives of this study were to determine if ABCB1 polymorphisms are associated with interindividual variability in sitagliptin pharmacokinetics, and if atorvastatin alters the pharmacokinetic disposition of sitagliptin in healthy volunteers. Methods In this open-label, randomized, two-phase crossover study, healthy volunteers were prospectively stratified according to ABCB1 1236/2677/3435 diplotype (n=9, CGC/CGC; n=10, CGC/TTT; and n=10, TTT/TTT). In one phase, participants received a single 100 mg dose of sitagliptin. In the other phase, participants received 40 mg of atorvastatin for five days, with a single 100 mg dose of sitagliptin administered on day 5. A 24 hour pharmacokinetic study followed each sitagliptin dose, and the study phases were separated by a 14-day washout period. Results Sitagliptin pharmacokinetic parameters did not differ significantly between ABCB1 CGC/CGC, CGC/TTT, and TTT/TTT diplotype groups during the monotherapy phase. Atorvastatin administration did not significantly affect sitagliptin pharmacokinetics, with GMRs (90% CIs) for sitagliptin Cmax, AUC0-∞, CLR, and fe of 0.93 (0.86, 1.01), 0.96 (0.91, 1.01), 1.02 (0.93, 1.12), and 0.98 (0.90, 1.06), respectively. Conclusions ABCB1 CGC/CGC, CGC/TTT, and TTT/TTT diplotypes did not influence sitagliptin pharmacokinetics in healthy volunteers. Furthermore, atorvastatin had no effect on the pharmacokinetics of sitagliptin in the setting of ABCB1 CGC/CGC, CGC/TTT, and TTT/TTT diplotypes. PMID:23407853

  16. Allium sativum L. Improves Visual Memory and Attention in Healthy Human Volunteers.

    PubMed

    Tasnim, Sara; Haque, Parsa Sanjana; Bari, Md Sazzadul; Hossain, Md Monir; Islam, Sardar Mohd Ashraful; Shahriar, Mohammad; Bhuiyan, Mohiuddin Ahmed; Bin Sayeed, Muhammad Shahdaat

    2015-01-01

    Studies have shown that Allium sativum L. (AS) protects amyloid-beta peptide-induced apoptosis, prevents oxidative insults to neurons and synapses, and thus prevent Alzheimer's disease progression in experimental animals. However, there is no experimental evidence in human regarding its putative role in memory and cognition. We have studied the effect of AS consumption by healthy human volunteers on visual memory, verbal memory, attention, and executive function in comparison to control subjects taking placebo. The study was conducted over five weeks and twenty volunteers of both genders were recruited and divided randomly into two groups: A (AS) and B (placebo). Both groups participated in the 6 computerized neuropsychological tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB) twice: at the beginning and after five weeks of the study. We found statistically significant difference (p < 0.05) in several parameters of visual memory and attention due to AS ingestion. We also found statistically nonsignificant (p > 0.05) beneficial effects on verbal memory and executive function within a short period of time among the volunteers. Study for a longer period of time with patients suffering from neurodegenerative diseases might yield more relevant results regarding the potential therapeutic role of AS.

  17. Effect of Crocus sativus L. (saffron) on coagulation and anticoagulation systems in healthy volunteers.

    PubMed

    Ayatollahi, Hossein; Javan, Atefeh Ordoei; Khajedaluee, Mohammad; Shahroodian, Masood; Hosseinzadeh, Hossein

    2014-04-01

    Saffron showed some effects on blood coagulation and platelet aggregation in in vitro and in vivo studies. In a clinical trial with a limited number volunteers, saffron tablets influenced on bleeding time. In this study, the effect of saffron on plasma level of fibrinogen, factor VII (as coagulant agent), C and S protein (as anti-coagulant agent), PT and PTT in a larger sample size was evaluated. The study was a double-blind, placebo-controlled study consisting of 1 week treatment with 200 mg and 400 mg saffron tablets. Sixty healthy volunteers (age range 20-50 years) were selected for the study. The volunteers were divided into three groups of 20 each. Group 1 received placebo; Groups 2 and 3 received 200 mg and 400 mg saffron tablets, respectively, for 7 days (1 tablet per day). Before and after 7 days treatment and also 1 month after that, blood samples were taken. The plasma levels of fibrinogen, factor VII, C and S protein, PT and PTT were evaluated. Statistical analysis showed no difference between groups for any of evaluated factors. This study rejected any effect of saffron with dose of 200 and 400 mg for 1 week on coagulant and anticoagulant system.

  18. Allium sativum L. Improves Visual Memory and Attention in Healthy Human Volunteers

    PubMed Central

    Tasnim, Sara; Haque, Parsa Sanjana; Bari, Md. Sazzadul; Hossain, Md. Monir; Islam, Sardar Mohd. Ashraful; Shahriar, Mohammad; Bhuiyan, Mohiuddin Ahmed; Bin Sayeed, Muhammad Shahdaat

    2015-01-01

    Studies have shown that Allium sativum L. (AS) protects amyloid-beta peptide-induced apoptosis, prevents oxidative insults to neurons and synapses, and thus prevent Alzheimer's disease progression in experimental animals. However, there is no experimental evidence in human regarding its putative role in memory and cognition. We have studied the effect of AS consumption by healthy human volunteers on visual memory, verbal memory, attention, and executive function in comparison to control subjects taking placebo. The study was conducted over five weeks and twenty volunteers of both genders were recruited and divided randomly into two groups: A (AS) and B (placebo). Both groups participated in the 6 computerized neuropsychological tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB) twice: at the beginning and after five weeks of the study. We found statistically significant difference (p < 0.05) in several parameters of visual memory and attention due to AS ingestion. We also found statistically nonsignificant (p > 0.05) beneficial effects on verbal memory and executive function within a short period of time among the volunteers. Study for a longer period of time with patients suffering from neurodegenerative diseases might yield more relevant results regarding the potential therapeutic role of AS. PMID:26351508

  19. A parallel design study to assess the bioequivalence of generic and branded hydroxychloroquine sulfate tablets in healthy volunteers.

    PubMed

    Liu, Y-M; Chen, Q; Zhang, M-Q; Liu, G-Y; Jia, J-Y; Pu, H-H; Liu, Y; Hu, C-Y; Lu, C; Wang, W; Cao, W-E; Song, B; Song, Y-X; Zhu, J-M; Yu, C

    2012-12-01

    Hydroxychloroquine (HCQ) is a racemic 4-aminoquinoline derivative that was first introduced as an antimalarial, and subsequently applied to the treatment of autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. Information on the pharmacokinetics of HCQ in healthy volunteers, especially in a Chinese population is limited, and this study was conducted to provide support for a generic product to obtain marketing authorization in China.The aim of the present study was to compare the pharmacokinetics and assess bioequivalence of a new generic test and the branded reference hydroxychloroquine sulfate tablets in healthy volunteers.This was a parallel, open-label, randomized, single-dose, 1-period fasting study. 54 healthy subjects were randomly assigned (1:1) to receive 200 mg hydroxychloroquine sulfate tablets of the test or the reference formulation. 15 blood samples were collected and whole blood concentrations of HCQ were determined by a validated liquid chromatography-isotopic dilution mass spectrometry method. Log-transformed Cmax and AUC0-24 values were used to test for bioequivalence. The 2 formulations were considered bioequivalent if 90% confidence intervals (CIs) for the log-transformed ratios of Cmax and AUC0-24 were within the predetermined bioequivalence range of 80-125%. Tolerability was evaluated throughout the study by vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms, and interviews with the subjects about adverse events.54 healthy subjects were enrolled and completed the study (mean [SD] age, height, body weight, and BMI were 23.9 [2.4] years, 168.9 [5.0] cm, 61.3 [5.4] kg, and 21.5 [1.7] kg/m2), 27 subjects per group. No formulation or sequence effects were observed. The mean values of Cmax and AUC0-24 for the test and reference formulations of HCQ (197.6 and 199.0 ng/mL, 2460.1 and 2468.3 ng/mL/h) were not significantly different. The 90% CIs of the ratios of Cmax and AUC0

  20. A parallel design study to assess the bioequivalence of generic and branded hydroxychloroquine sulfate tablets in healthy volunteers.

    PubMed

    Liu, Y-M; Chen, Q; Zhang, M-Q; Liu, G-Y; Jia, J-Y; Pu, H-H; Liu, Y; Hu, C-Y; Lu, C; Wang, W; Cao, W-E; Song, B; Song, Y-X; Zhu, J-M; Yu, C

    2012-12-01

    Hydroxychloroquine (HCQ) is a racemic 4-aminoquinoline derivative that was first introduced as an antimalarial, and subsequently applied to the treatment of autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. Information on the pharmacokinetics of HCQ in healthy volunteers, especially in a Chinese population is limited, and this study was conducted to provide support for a generic product to obtain marketing authorization in China.The aim of the present study was to compare the pharmacokinetics and assess bioequivalence of a new generic test and the branded reference hydroxychloroquine sulfate tablets in healthy volunteers.This was a parallel, open-label, randomized, single-dose, 1-period fasting study. 54 healthy subjects were randomly assigned (1:1) to receive 200 mg hydroxychloroquine sulfate tablets of the test or the reference formulation. 15 blood samples were collected and whole blood concentrations of HCQ were determined by a validated liquid chromatography-isotopic dilution mass spectrometry method. Log-transformed Cmax and AUC0-24 values were used to test for bioequivalence. The 2 formulations were considered bioequivalent if 90% confidence intervals (CIs) for the log-transformed ratios of Cmax and AUC0-24 were within the predetermined bioequivalence range of 80-125%. Tolerability was evaluated throughout the study by vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms, and interviews with the subjects about adverse events.54 healthy subjects were enrolled and completed the study (mean [SD] age, height, body weight, and BMI were 23.9 [2.4] years, 168.9 [5.0] cm, 61.3 [5.4] kg, and 21.5 [1.7] kg/m2), 27 subjects per group. No formulation or sequence effects were observed. The mean values of Cmax and AUC0-24 for the test and reference formulations of HCQ (197.6 and 199.0 ng/mL, 2460.1 and 2468.3 ng/mL/h) were not significantly different. The 90% CIs of the ratios of Cmax and AUC0

  1. Biomarkers for the effects of cannabis and THC in healthy volunteers

    PubMed Central

    Zuurman, Lineke; Ippel, Annelies E; Moin, Eduard; van Gerven, Joop M A

    2009-01-01

    An increasing number of novel therapeutic agents are targeted at cannabinoid receptors. Drug development programmes of new cannabinoid drugs may be facilitated by the identification of useful biomarkers. This systemic literature review aims to assess the usefulness of direct biomarkers for the effects of cannabis and tetrahydrocannabinol (THC) in healthy volunteers. One hundred and sixty-five useful articles were found that investigated the acute effects of cannabis or THC on the central nervous system (CNS) and heart rate in healthy volunteers. Three hundred and eighteen tests (or test variants) were grouped in test clusters and functional domains, to allow their evaluation as a useful biomarker and to study their dose–response effects. Cannabis/THC affected a wide range of CNS domains. In addition to heart rate, subjective effects were the most reliable biomarkers, showing significant responses to cannabis in almost all studies. Some CNS domains showed indications of depression at lower and stimulation at higher doses. Subjective effects and heart rate are currently the most reliable biomarkers to study the effect of cannabis. Cannabis affects most CNS domains, but too many different CNS tests are used to quantify the drug–response relationships reliably. Test standardization, particularly in motor and memory domains, may reveal additional biomarkers. PMID:19133057

  2. Bioequivalence study of 500 mg cefuroxime axetil film-coated tablets in healthy volunteers.

    PubMed

    Kaza, Michał; Leś, Andrzej; Serafin-Byczak, Krystyna; Ksycińska, Hanna; Rudzki, Piotr J; Gutkowskpi, Piotr; Drewniak, Tomasz; Gutkowska, Anna; Tarasiuk, Andrzej; Piatkowska-Chabuda, Ewa; Skowrońska-Smolak, Małgorzata; Wilkowska, Ewa

    2012-01-01

    The aim of the study was to investigate the bioavailability of a generic product of 500 mg cefuroxime axetil film-coated tablets (test) as compared to that of a branded product (reference) at the same strength to determine bioequivalence and to apply for regulatory approval. The secondary objective of the study was to evaluate tolerability of both products. A double blinded, randomized, crossover, two-period, single-dose, comparative study was conducted in Caucasian healthy volunteers in fasting conditions. A single oral dose administration of the test or reference product was followed by 7-day wash-out period. The cefuroxime concentration was determined using a validated HPLC-UV method. The results of the single-dose study in healthy volunteers indicated that the film-coated tablets of Tarsime 500 mg manufactured by Tarchomińskie Zakłady Farmaceutyczne Polfa S.A. (test product) are bioequivalent to those of Zinnat manufactured by GlaxoSmithKline Export Ltd. (reference product). Both products were well tolerated.

  3. Caffeine and taurine containing energy drink increases left ventricular contractility in healthy volunteers.

    PubMed

    Doerner, Jonas M; Kuetting, Daniel L; Luetkens, Julian A; Naehle, Claas P; Dabir, Darius; Homsi, Rami; Nadal, Jennifer; Schild, Hans H; Thomas, Daniel K

    2015-03-01

    To investigate the impact of a caffeine and taurine containing energy drink (ED) on myocardial contractility in healthy volunteers using cardiac MR and cardiac MR based strain analysis. 32 healthy volunteers (mean age 28 years) were investigated before and 1 h after consumption of a caffeine and taurine containing ED. For assessment of global cardiac functional parameters balanced SSFP-Cine imaging was performed, whereas CSPAMM tagging was used to evaluate global and regional myocardial strain. In addition, ten randomly chosen subjects were investigated once more using a caffeine only protocol to further evaluate the effect of caffeine solely. Heart rate and blood pressure were recorded throughout all studies. ED consumption led to a significant increase in peak systolic strain (PSS) and peak systolic strain rate (PSSR) 1 h after consumption (PSS: w/o ED -22.8 ± 2.1%; w ED -24.3 ± 2.4%, P = <0.0001 and PSSR: w/o ED -1.2 ± 0.1 1/s; w ED -1.3 ± 0.2 1/s, P = 0.0056), which was not observed in the caffeine only group. In contrast, global left ventricular function was unchanged (P = 0.2076). No significant changes of vital parameters and diastolic filling pattern were detected 1 h after ED consumption. Consumption of a caffeine and taurine containing ED results in a subtle, but significant increase of myocardial contractility 1 h after consumption. PMID:25425431

  4. Lorazepam 0.25 mg twice a day improves aspects of psychometric performance in healthy volunteers.

    PubMed

    Bourin, M; Colombel, M C; Malinge, M

    1995-01-01

    The effects of lorazepam (0.25 mg) twice a day on several cognitive and performance tasks, pictures test, digit-symbol substitution test (DSST), choice reaction time (CRT) and critical flicker fusion (CFF), were investigated in healthy students. A double-blind independent group design was used to compare placebo and lorazepam (30 volunteers in each group). After randomisation, all subjects received placebo for 3 days (D), followed by 14 days of treatment, with either lorazepam or placebo. Subjects completed a battery of tests at Do, then D(3), D(7) , D(10) and D(14). D(3) performance was poorer in the lorazepam group except for CFF (ascending values and total values), yet the only significant improvement was in total reaction time on the CRT test. However, a significant improvement of performance was shown at D(7), D(10) and D(14) in the lorazepam group compared with the control group (except in recognition reaction time). The current study shows that low repeated doses of lorazepam are able to produce small improvements in some aspects of psychomotor and cognitive functions in healthy volunteers. Different points are discussed to explain the performance improvement: training effect, tolerance effect, partial inverse agonist effect and the possible release of cholecystokinin.

  5. Neurobehavioral and Cognitive Changes Induced by Sleep Deprivation in Healthy Volunteers.

    PubMed

    Cassé-Perrot, Catherine; Lanteaume, Laura; Deguil, Julie; Bordet, Régis; Auffret, Alexandra; Otten, Lisa; Blin, Olivier; Bartrés-Faz, David; Micallef, Joëlle

    2016-01-01

    To this day, the pharmacological treatment of Alzheimer's disease remains limited to the temporary stabilisation of cognitive decline and the reduction of neuropsychiatric symptoms. It is moreover with great difficulty to predict and select promising drug candidates in the early stages of the discovery and developmental process. In this context, scientists have developed new experimental paradigms to artificially induce transient cognitive impairments in healthy volunteers akin to those observed in Alzheimer's disease, i.e. the Cognitive Challenge Models. In the last decade, a great amount of literature on Sleep Deprivation was published which mainly focused on the consequences of sleep loss for public health. However, sleep deprivation paradigm may also be regarded as a cognitive challenge model. It is commonly accepted that sleep deprivation induces cognitive impairments related to a global decrease in vigilance, while in fact, there is a controversial approach related to the selective effects on cognitive functions. The identification and validation of cognitive challenge models in healthy volunteers are suitable in early clinical development of drugs to determine the 'hint of efficacy' of drug candidates. The present review aims at exploring in detail the methods, designs and cognitive paradigms used in non pharmacological sleep deprivation studies. Sleep deprivation can be induced by different methods. Probing the four main cognitive functions will allow identifying the extent to which different sleep deprivation designs selectively compromise executive function, working memory, episodic memory and attention. Findings will be discussed in line with cognitive processing levels that are required according to the tasks. PMID:27189463

  6. Distribution and Respiratory Activity of Mycobacteria in Household Water System of Healthy Volunteers in Japan

    PubMed Central

    Ichijo, Tomoaki; Izumi, Yoko; Nakamoto, Sayuri; Yamaguchi, Nobuyasu; Nasu, Masao

    2014-01-01

    The primary infectious source of nontuberculous mycobacteria (NTM), which are known as opportunistic pathogens, appears to be environmental exposure, and it is important to reduce the frequency of exposure from environmental sources for preventing NTM infections. In order to achieve this, the distribution and respiratory activity of NTM in the environments must be clarified. In this study, we determined the abundance of mycobacteria and respiratory active mycobacteria in the household water system of healthy volunteers using quantitative PCR and a fluorescent staining method, because household water has been considered as one of the possible infectious sources. We chose healthy volunteer households in order to lessen the effect of possible residential contamination from an infected patient. We evaluated whether each sampling site (bathroom drain, kitchen drain, bath heater pipe and showerhead) have the potential to be the sources of NTM infections. Our results indicated that drains in the bathroom and kitchen sink are the niche for Mycobacterium spp. and M. avium cells were only detected in the bathtub inlet. Both physicochemical and biologic selective pressures may affect the preferred habitat of Mycobacterium spp. Regional differences also appear to exist as demonstrated by the presence (US) or absence (Japan) of Mycobacterium spp. on showerheads. Understanding of the country specific human activities and water usage will help to elucidate the infectious source and route of nontuberculous mycobacterial disease. PMID:25350137

  7. The cerebellum link to neuroticism: a volumetric MRI association study in healthy volunteers.

    PubMed

    Schutter, Dennis J L G; Koolschijn, P Cédric M P; Peper, Jiska S; Crone, Eveline A

    2012-01-01

    Prior research suggests an association between reduced cerebellar volumes and symptoms of depression and anxiety in patients with mood disorders. However, whether a smaller volume in itself reflects a neuroanatomical correlate for increased susceptibility to develop mood disorders remains unclear. The aim of the present study was to examine the relationship between cerebellar volume and neurotic personality traits in a non-clinical subject sample. 3T Structural magnetic resonance imaging scans were acquired, and trait depression and anxiety scales of the revised NEO personality inventory were assessed in thirty-eight healthy right-handed volunteers. Results showed that cerebellar volume corrected for total brain volume was inversely associated with depressive and anxiety-related personality traits. Cerebellar gray and white matter contributed equally to the observed associations. Our findings extend earlier clinical observations by showing that cerebellar volume covaries with neurotic personality traits in healthy volunteers. The results may point towards a possible role of the cerebellum in the vulnerability to experience negative affect. In conclusion, cerebellar volumes may constitute a clinico-neuroanatomical correlate for the development of depression- and anxiety-related symptoms.

  8. The Cerebellum Link to Neuroticism: A Volumetric MRI Association Study in Healthy Volunteers

    PubMed Central

    Schutter, Dennis J. L. G.; Koolschijn, P. Cédric M. P.; Peper, Jiska S.; Crone, Eveline A.

    2012-01-01

    Prior research suggests an association between reduced cerebellar volumes and symptoms of depression and anxiety in patients with mood disorders. However, whether a smaller volume in itself reflects a neuroanatomical correlate for increased susceptibility to develop mood disorders remains unclear. The aim of the present study was to examine the relationship between cerebellar volume and neurotic personality traits in a non-clinical subject sample. 3T Structural magnetic resonance imaging scans were acquired, and trait depression and anxiety scales of the revised NEO personality inventory were assessed in thirty-eight healthy right-handed volunteers. Results showed that cerebellar volume corrected for total brain volume was inversely associated with depressive and anxiety-related personality traits. Cerebellar gray and white matter contributed equally to the observed associations. Our findings extend earlier clinical observations by showing that cerebellar volume covaries with neurotic personality traits in healthy volunteers. The results may point towards a possible role of the cerebellum in the vulnerability to experience negative affect. In conclusion, cerebellar volumes may constitute a clinico-neuroanatomical correlate for the development of depression- and anxiety-related symptoms. PMID:22615955

  9. Biomarkers for the effects of cannabis and THC in healthy volunteers.

    PubMed

    Zuurman, Lineke; Ippel, Annelies E; Moin, Eduard; van Gerven, Joop M A

    2009-01-01

    An increasing number of novel therapeutic agents are targeted at cannabinoid receptors. Drug development programmes of new cannabinoid drugs may be facilitated by the identification of useful biomarkers. This systemic literature review aims to assess the usefulness of direct biomarkers for the effects of cannabis and tetrahydrocannabinol (THC) in healthy volunteers. One hundred and sixty-five useful articles were found that investigated the acute effects of cannabis or THC on the central nervous system (CNS) and heart rate in healthy volunteers. Three hundred and eighteen tests (or test variants) were grouped in test clusters and functional domains, to allow their evaluation as a useful biomarker and to study their dose-response effects. Cannabis/THC affected a wide range of CNS domains. In addition to heart rate, subjective effects were the most reliable biomarkers, showing significant responses to cannabis in almost all studies. Some CNS domains showed indications of depression at lower and stimulation at higher doses. Subjective effects and heart rate are currently the most reliable biomarkers to study the effect of cannabis. Cannabis affects most CNS domains, but too many different CNS tests are used to quantify the drug-response relationships reliably. Test standardization, particularly in motor and memory domains, may reveal additional biomarkers. PMID:19133057

  10. Acute effects of exposure to air contaminants in a sawmill on healthy volunteers.

    PubMed Central

    Dahlqvist, M; Palmberg, L; Malmberg, P; Sundblad, B M; Ulfvarson, U; Zhiping, W

    1996-01-01

    OBJECTIVES: To study whether air contaminants in sawmills can induce acute changes in the upper and lower airways of previously non-exposed subjects. METHODS: Nineteen healthy volunteers were examined to find the concentration of interleukin 6 (IL-6) in nasal lavage fluid and lung function before and after five hour exposure to dusts and fumes generated in a sawmill where timber from Scots pine was sawed. When exposed, the subjects had respirators with and without a particle filter. RESULTS: The median for daily time weighted average concentration of total dust for subjects with respirators without a filter was 0.13 mg/m3, which was significantly higher than the median of 0.04 mg/m3 for subjects who had respirators with a filter. The median for the concentration of IL-6 in the nasal lavage fluid increased after exposure from 0.5 to 5.9 pg/ml in subjects with respirators without a particle filter (P < 0.05). The increase of the concentration of IL-6 was significantly correlated with the dust concentration. A decrease in transfer factor of the lung was significantly correlated with daily time weighted average concentrations of terpenes. CONCLUSION: The findings suggest that healthy volunteers, exposed to air contaminants in a sawmill, show a slight inflammatory reaction. Also, the results of the study indicate the importance of decreasing the concentrations of wood dust in the work environment. PMID:8882114

  11. Caffeine and taurine containing energy drink increases left ventricular contractility in healthy volunteers.

    PubMed

    Doerner, Jonas M; Kuetting, Daniel L; Luetkens, Julian A; Naehle, Claas P; Dabir, Darius; Homsi, Rami; Nadal, Jennifer; Schild, Hans H; Thomas, Daniel K

    2015-03-01

    To investigate the impact of a caffeine and taurine containing energy drink (ED) on myocardial contractility in healthy volunteers using cardiac MR and cardiac MR based strain analysis. 32 healthy volunteers (mean age 28 years) were investigated before and 1 h after consumption of a caffeine and taurine containing ED. For assessment of global cardiac functional parameters balanced SSFP-Cine imaging was performed, whereas CSPAMM tagging was used to evaluate global and regional myocardial strain. In addition, ten randomly chosen subjects were investigated once more using a caffeine only protocol to further evaluate the effect of caffeine solely. Heart rate and blood pressure were recorded throughout all studies. ED consumption led to a significant increase in peak systolic strain (PSS) and peak systolic strain rate (PSSR) 1 h after consumption (PSS: w/o ED -22.8 ± 2.1%; w ED -24.3 ± 2.4%, P = <0.0001 and PSSR: w/o ED -1.2 ± 0.1 1/s; w ED -1.3 ± 0.2 1/s, P = 0.0056), which was not observed in the caffeine only group. In contrast, global left ventricular function was unchanged (P = 0.2076). No significant changes of vital parameters and diastolic filling pattern were detected 1 h after ED consumption. Consumption of a caffeine and taurine containing ED results in a subtle, but significant increase of myocardial contractility 1 h after consumption.

  12. Detection of human papillomavirus DNA in plucked hairs from renal transplant recipients and healthy volunteers.

    PubMed

    Boxman, I L; Berkhout, R J; Mulder, L H; Wolkers, M C; Bouwes Bavinck, J N; Vermeer, B J; ter Schegget, J

    1997-05-01

    We have previously detected a group of human papillomaviruses originally found in skin lesions of epidermodysplasia verruciformis (EV) patients in skin cancers from renal transplant recipients and from non-immunosuppressed patients. The reservoir of EV-HPVs is still unknown. In the current study we investigated whether EV-HPV DNA can be detected in plucked hairs from renal transplant recipients and healthy volunteers. Hairs were plucked from eyebrows, scalp, arms, and/or legs and DNA was subsequently isolated. To detect EV-HPV, we used nested PCR with degenerate primers located in the HPV L1 open reading frame. HPV DNA was detected in hairs from one or more sites in all 26 renal transplant recipients tested. Forty-five of 49 samples (92%) from these 26 patients were positive. The HPV type was successfully determined by sequencing in 38 samples, and all types belonged to the EV-HPVs. In ten of 22 healthy volunteers (45%), EV-HPV DNA was also detected in hairs from one or more sites. Twenty of 38 samples (53%) were positive, of which 17 samples were typed as EV-HPV types. These findings indicate that EV-HPV is subclinically present in the skin of the general population. Immunosuppression may lead to activation of the virus, explaining the finding that the apparent prevalence of EV-HPV in plucked hairs from renal transplant patients is higher than in those from the volunteers. If a dose-response situation exists for the carcinogenic potential of HPV infection, this finding may be relevant to the increased risk of skin cancer in this group of patients.

  13. Pharmacokinetics and Pharmacodynamics of Intranasal Insulin Spray (Nasulin™) Administered to Healthy Male Volunteers:

    PubMed Central

    Leary, Andrew C.; Dowling, Muiris; Cussen, Kathleen; O'Brien, Jackie; Stote, Robert M.

    2008-01-01

    Background The pharmacokinetics and pharmacodynamics of a Bentley Pharmaceuticals proprietary intranasal (IN) insulin formulation (Nasulin™) were studied in healthy volunteers. Methods Thirteen fasting healthy male volunteers received five doses of medication (one dose of 4 international units [IU] subcutaneous (SC) regular insulin and four doses of 25 IU IN insulin) at least 48 h apart. Serum insulin, serum C-peptide, and plasma glucose were measured in the 4 h after dosing. Profiles were compared for IN insulin spray following administration into the dominant nostril (more open at time of dosing) and into the nondominant nostril (less open at time of dosing). Results The formulation was generally well tolerated. A rise in serum insulin levels accompanied by a decrease in plasma glucose was seen following all doses. For IN doses, peak insulin levels were generally attained in 10–20 min and remained elevated for approximately 40–50 min; the resultant effect on glucose peaked at 40 min and waned approximately 2 h postdosing. As reported in other studies, the interindividual response to insulin was variable. The comparative absorption of IN insulin relative to SC insulin was 12.0% (dominant nostril) or 15.4% (nondominant nostril) over 2 h. This increased somewhat if sneezers and volunteers with moderately blocked nostrils were removed from the analysis. Conclusions This IN formulation was generally well tolerated and relatively well absorbed. While both insulin data (maximal plasma concentration and area under the plasma concentration time curve) and glucose data (% fall) support a trend toward better absorption from the nondominant nostril, this did not reach statistical significance. Nasulin can be administered without reference to the nasal cycle. PMID:19885293

  14. Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers.

    PubMed

    Gota, Vikram S; Maru, Girish B; Soni, Tejal G; Gandhi, Tejal R; Kochar, Nitin; Agarwal, Manish G

    2010-02-24

    Curcumin is the lipid-soluble antioxidant compound obtained from the rhizome of Curcuma longa Linn, also known as turmeric. Curcumin targets multiple chemotherapeutic and inflammatory pathways and has demonstrated safety and tolerability in humans, supporting its potential as a therapeutic agent; however, the clinical literature lacks conclusive evidence supporting its use as a therapeutic agent due to its low bioavailability in humans. The purpose of this study was to quantify plasma levels of free curcumin after dosing of a solid lipid curcumin particle (SLCP) formulation versus unformulated curcumin in healthy volunteers and to determine its tolerability and dose-plasma concentration relationship in late-stage osteosarcoma patients. Doses of 2, 3, and 4 g of SLCP were evaluated in 11 patients with osteosarcoma. Plasma curcumin levels were measured using a validated high-performance liquid chromatography method. The limit of detection of the assay was 1 ng/mL of curcumin. In healthy subjects, the mean peak concentration of curcumin achieved from dosing 650 mg of SLCP was 22.43 ng/mL, whereas plasma curcumin from dosing an equal quantity of unformulated 95% curcuminoids extract was not detected. In both healthy individuals and osteosarcoma patients, high interindividual variability in pharmacokinetics and nonlinear dose dependency was observed, suggesting potentially complex absorption kinetics. Overall, good tolerability was noted in both healthy and osteosarcoma groups. PMID:20092313

  15. Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers.

    PubMed

    Gota, Vikram S; Maru, Girish B; Soni, Tejal G; Gandhi, Tejal R; Kochar, Nitin; Agarwal, Manish G

    2010-02-24

    Curcumin is the lipid-soluble antioxidant compound obtained from the rhizome of Curcuma longa Linn, also known as turmeric. Curcumin targets multiple chemotherapeutic and inflammatory pathways and has demonstrated safety and tolerability in humans, supporting its potential as a therapeutic agent; however, the clinical literature lacks conclusive evidence supporting its use as a therapeutic agent due to its low bioavailability in humans. The purpose of this study was to quantify plasma levels of free curcumin after dosing of a solid lipid curcumin particle (SLCP) formulation versus unformulated curcumin in healthy volunteers and to determine its tolerability and dose-plasma concentration relationship in late-stage osteosarcoma patients. Doses of 2, 3, and 4 g of SLCP were evaluated in 11 patients with osteosarcoma. Plasma curcumin levels were measured using a validated high-performance liquid chromatography method. The limit of detection of the assay was 1 ng/mL of curcumin. In healthy subjects, the mean peak concentration of curcumin achieved from dosing 650 mg of SLCP was 22.43 ng/mL, whereas plasma curcumin from dosing an equal quantity of unformulated 95% curcuminoids extract was not detected. In both healthy individuals and osteosarcoma patients, high interindividual variability in pharmacokinetics and nonlinear dose dependency was observed, suggesting potentially complex absorption kinetics. Overall, good tolerability was noted in both healthy and osteosarcoma groups.

  16. Molecular characterization of skin microbiota between cancer cachexia patients and healthy volunteers.

    PubMed

    Li, Wei; Han, Lei; Yu, Pengbo; Ma, Chaofeng; Wu, Xiaokang; Moore, John E; Xu, Jiru

    2014-04-01

    Systemic inflammation contributes to both the development of cancer and of cachexia. The microenvironment of bacterial habitats might be changed during the progression of cancer cachexia. The aim of this study was to quantitatively and qualitatively compare the composition of the skin microbiota between cancer cachexia patients and healthy volunteers. Cutaneous bacteria were swabbed at the axillary fossa of 70 cancer cachexia patients and 34 healthy individuals from China. Nested-PCR-denaturing gradient gel electrophoresis (PCR-DGGE) with primers specifically targeting V3 region and quantitative PCR (qPCR) for total bacteria, Corynebacterium spp., Staphylococcus spp., and Staphylococcus epidermidis were performed on all samples. Barcoded 454 pyrosequencing of the V3-V4 regions was performed on 30 randomly selected samples. By comparing diversity and richness indices, we found that the skin microbiome of cachectic cancer patients is less diverse than that of healthy participants, though these differences were not significant. The main microbes that reside on human skin were divided into four phyla: Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes. Staphylococcus spp. and Corynebacterium spp. were the dominant bacteria at the genus level. Significantly fewer Corynebacterium spp. had been observed in cachexia patients compared to healthy subjects. These results suggest that the presence of cancer and cachexia alters human skin bacterial communities. Understanding the changes in microbiota during cancer cachexia may lead to new insights into the syndrome.

  17. Molecular characterization of skin microbiota between cancer cachexia patients and healthy volunteers.

    PubMed

    Li, Wei; Han, Lei; Yu, Pengbo; Ma, Chaofeng; Wu, Xiaokang; Moore, John E; Xu, Jiru

    2014-04-01

    Systemic inflammation contributes to both the development of cancer and of cachexia. The microenvironment of bacterial habitats might be changed during the progression of cancer cachexia. The aim of this study was to quantitatively and qualitatively compare the composition of the skin microbiota between cancer cachexia patients and healthy volunteers. Cutaneous bacteria were swabbed at the axillary fossa of 70 cancer cachexia patients and 34 healthy individuals from China. Nested-PCR-denaturing gradient gel electrophoresis (PCR-DGGE) with primers specifically targeting V3 region and quantitative PCR (qPCR) for total bacteria, Corynebacterium spp., Staphylococcus spp., and Staphylococcus epidermidis were performed on all samples. Barcoded 454 pyrosequencing of the V3-V4 regions was performed on 30 randomly selected samples. By comparing diversity and richness indices, we found that the skin microbiome of cachectic cancer patients is less diverse than that of healthy participants, though these differences were not significant. The main microbes that reside on human skin were divided into four phyla: Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes. Staphylococcus spp. and Corynebacterium spp. were the dominant bacteria at the genus level. Significantly fewer Corynebacterium spp. had been observed in cachexia patients compared to healthy subjects. These results suggest that the presence of cancer and cachexia alters human skin bacterial communities. Understanding the changes in microbiota during cancer cachexia may lead to new insights into the syndrome. PMID:24402361

  18. Noninvasive estimation of tissue edema in healthy volunteers and in patients suffering from heart failure

    NASA Astrophysics Data System (ADS)

    Gurfinkel, Yuri I.; Mikhailov, Valery M.; Kudutkina, Marina I.

    2004-06-01

    Capillaries play a critical role in cardiovascular function as the point of exchange of nutrients and waste products between tissues and circulation. A common problem for healthy volunteers examined during isolation, and for the patients suffering from heart failure is a quantitative estimation tissue oedema. Until now, objective assessment body fluids retention in tissues did not exist. Optical imaging of living capillaries is a challenging and medically important scientific problem. Goal of the investigation was to study dynamic of microcriculation parameters including tissue oedema in healthy volunteers during extended isolation and relative hypokinesia as a model of mission to the International Space Station. The other aim was to study dynamic of microcirculation parameters including tissue oedema in patients suffering from heart failure under treatment. Healthy volunteers and patients. We studied four healthy male subjects at the age of 41, 37, 40, and 48 before the experiment (June 1999), and during the 240-d isolation period starting from July3, 1999. Unique hermetic chambers with artidicial environmental parameters allowed performing this study with maximum similarity to real conditions in the International Space Station (ISS). With the regularity of 3 times a week at the same time, each subject recorded three video episodes with the total length of one-minute using the optical computerized capillaroscope for noninvasive measurement of the capillary diameters sizes, capillary blood velocity as well as the size of the perivascular zone. All this parameters of microcirculation determined during three weeks in 15 patients (10 male, 5 female, aged 62,2+/-8,8) suffering from heart failure under Furosemid 40 mg 2 times a week, as diuretic. Results. About 1500 episodes recorded on laser disks and analyzed during this experiment. Every subject had wave-like variations of capillary blood velocity within the minute, week, and month ranges. It was found that the

  19. Evaluation of Trigeminal Sensitivity to Ammonia in Asthmatics and Healthy Human Volunteers

    PubMed Central

    Petrova, Maja; Diamond, Jeanmarie; Schuster, Benno; Dalton, Pamela

    2009-01-01

    Background Asthmatics often report the triggering or exacerbation of respiratory symptoms following exposure to airborne irritants, which in some cases may result from stimulation of irritant receptors in the upper airways inducing reflexive broncho-constriction. Ammonia (NH3) is a common constituent of commercially available household products, and in high concentration has the potential to elicit sensory irritation in the eyes and upper respiratory tract of humans. The goal of the present study was to evaluate the irritation potential of ammonia in asthmatics and healthy volunteers and to determine whether differences in nasal or ocular irritant sensitivity to ammonia between these two groups could account for the exacerbation of symptoms reported by asthmatics following exposure to an irritant. Methods 25 healthy and 15 mild/moderate persistent asthmatic volunteers, with reported sensitivity to household cleaning products, were evaluated for their sensitivity to the ocular and nasal irritancy of NH3. Lung function was evaluated at baseline and multiple time points following exposure. Results Irritation thresholds did not differ between asthmatics and healthy controls, nor did ratings of odor intensity, annoyance and irritancy following exposure to NH3 concentrations at and above the irritant threshold for longer periods of time (30 sec).Importantly, no changes in lung function occurred following exposure to NH3 for any individuals in either group. Conclusion Despite heightened symptom reports to environmental irritants among asthmatics, the ocular and nasal trigeminal system of mild-moderate asthmatics does not appear to be more sensitive or more reactive than that of non-asthmatics, nor does short duration exposure to ammonia at irritant levels induce changes in lung function. At least in brief exposures, the basis for some asthmatics to experience adverse responses to volatile compounds in everyday life may arise from factors other than trigeminally

  20. Evaluation of the functional efficacy of an antioxidative probiotic in healthy volunteers

    PubMed Central

    Songisepp, Epp; Kals, Jaak; Kullisaar, Tiiu; Mändar, Reet; Hütt, Pirje; Zilmer, Mihkel; Mikelsaar, Marika

    2005-01-01

    Background In persons without clinical symptom it is difficult to assess an impact of probiotics regarding its effect on health. We evaluated the functional efficacy of the probiotic Lactobacillus fermentum ME-3 in healthy volunteers by measuring the influence of two different formulations on intestinal lactoflora, fecal recovery of the probiotic strain and oxidative stress markers of blood and urine after 3 weeks consumption. Methods Two 3-week healthy volunteer trials were performed. Open placebo controlled (OPC) study participants (n = 21) consumed either goat milk or by L. fermentum ME-3 fermented goat milk (daily dose 11.8 log CFU (Colony Forming Units). Double blind randomised placebo controlled (DBRP) study participants (n = 24) received either capsules with L. fermentum ME-3 (daily of dose 9.2 CFU) or placebo capsules. The faecal lactoflora composition, faecal ME-3 recovery, effect of the consumption on intestinal lactoflora, and oxidative stress markers of blood (total antioxidative activity; total antioxidative status and glutathione red-ox ratio) was measured. Results ME-3 was well tolerated and a significant increase in total faecal lactobacilli yet no predominance of ME-3 was detected in all study groups. Faecal recovery of ME-3 was documented by molecular methods only in fermented milk group, however the significant improvement of blood TAA (Total Antioxidative Activity) and TAS (Total Antioxidative Status) indices was seen both in case of fermented goat milk and capsules", yet glutathione re-ox ratio values decreased only in case of fermented by ME-3 goat milk. Conclusion The functional efficacy of both consumed formulations of an antioxidative probiotic L. fermentum ME-3 is proved by the increase of the intestinal lactobacilli counts providing putative defence against enteric infections and by reduction of the oxidative stress indices of blood and urine of healthy volunteers. In non-diseased host the probiotic health claims can be assessed by

  1. Effects of smoking on renal hemodynamics in healthy volunteers and in patients with glomerular disease.

    PubMed

    Ritz, E; Benck, U; Franek, E; Keller, C; Seyfarth, M; Clorius, J

    1998-10-01

    Patients with renal disease who smoke have a poor renal functional prognosis, but the mechanisms involved have not been explored. In this controlled study, the effects of smoking and sham smoking were compared in 15 healthy normotensive volunteers. All were occasional smokers and abstained from smoking for 48 h as documented by urinary cotinine measurements. These data were compared with those of seven patients with biopsy-confirmed IgA glomerulonephritis, also occasional smokers. Renal clearance examinations were obtained after hydration in the supine position before and while smoking two cigarettes or sham cigarettes in random order on 2 consecutive days. GFR and effective renal plasma flow were determined using In111-diethylenetriamine penta-acetic acid and 131I-hippurate with a dual tracer infusion clearance technique. In an ancillary study with six volunteers, the effect of smoking was compared with the effect of nicotine-containing chewing gum. In healthy volunteers, sham smoking caused a minor but significant increase of mean arterial pressure (MAP) and GFR with no significant change of effective renal plasma flow, filtration fraction (FF), or renovascular resistance. Smoking caused a significant and more marked increase of MAP (from baseline 92.8+/-8.98 to 105+/-7.78 mmHg) and heart rate (from 61.7+/-7.52 to 86.4+/-9.87 min(-1)), accompanied by a significant increase in arginine vasopressin (from 1.27+/-0.72 to 19.9+/-27.2 pg/ml) and epinephrine (from 37+/-13 to 140+/-129 pg/ml). During smoking, GFR decreased in all but one volunteer (from 120+/-17.7 to 102+/-19.3 ml/min per 1.73 m2), and this was accompanied by a significant decrease of FF (from 21.3+/-4.24 to 17.4+/-3.41%) and an increase in renovascular resistance (from 97.6+/-27.2 to 108+/-30.4 mmHg x min/ml per 1.73 m2). These findings were reproduced with nicotine-containing chewing gum. In contrast, when patients with IgA glomerulonephritis smoked, a similar increment in MAP was noted, the changes of

  2. Disposition kinetics of selenium in healthy volunteers following therapeutic shampoo treatment.

    PubMed

    Noisel, Nolwenn; Bouchard, Michèle; Carrier, Gaétan

    2010-05-01

    This study was aimed at documenting the kinetic time courses of selenium (Se) in accessible biological matrices of volunteers following controlled applications of therapeutic shampoo containing Se, to better elucidate the mechanisms by which shampoo-Se accumulates in hair and hence estimate the contribution of this source to total Se body burden. Ten healthy volunteers were exposed to Se-shampoo three times a week over a month. Blood, hair and toenail concentrations along with daily urinary excretions were repeatedly measured over an 18-month period following the onset of application. Over the entire study period, blood concentrations of Se (range: 127-233μg/l) and daily urinary excretions (range: 11.9-150μg/d) remained within baseline range of the general population. Conversely, during shampoo application, mean Se concentrations in hair reached transitional levels of 89μg/g while, following cessation of treatment, a mono-exponential decrease was observed with a mean half-life of 4.5 weeks. Two of the volunteers also exhibited an increase in toenail concentrations of Se during the study period. Results show that Se-shampoo does not contribute significantly to total Se body burden, as assessed from blood and urine levels. Differences observed between blood and urine time courses as compared to hair profiles and the presence of Se on hair grown before treatment indicates an adsorption on hair; however, the gradual decrease in Se concentrations in successive centimeters of hair grown following the application period suggests a concomitant absorption from the scalp during treatment with subsequent excretion in hair.

  3. Increase in body mass index from normal weight to overweight in a cross-sectional sample of healthy research volunteers.

    PubMed

    Courville, Amber B; DiVito, Meagan; Moyer, Lindsay; Rossinoff, Anna; Royster, Caitlin; Psota, Tricia; Ayres, Elaine; Zambell, Kirsten L

    2014-12-01

    Current literature provides limited information about healthy volunteers serving as controls for biomedical research. This study describes trends in body mass index (BMI), a ratio of weight to height (kilograms per square meter), of the population of healthy volunteers at the National Institutes of Health Clinical Center (NIH CC) and compares these trends to a nationally representative sample, as reported by the National Health and Nutrition Examination Survey. We hypothesized that BMI trends at the NIH CC would follow those of the US population. This cross-sectional study examined the BMI of healthy volunteers at the NIH CC from 1976 to 1980, 1981 to 1987, 1988 to 1994, 1995 to 1998 and for all subsequent two-year periods onward until 2012. Study data were extracted from the NIH Biomedical Translational Research Information System. Subjects were selected based on a discharge code of "volunteer." Descriptive statistics of volunteers at the NIH CC were calculated for height, weight, age-adjusted BMI, age, and sex, and associations between categorical variables were analyzed using the χ2 test. Differences between BMI categories or periods for continuous independent variables were assessed using Kruskal-Wallis and post hoc Tamhane T2 tests. The 13 898 healthy volunteers with median age of 34 years were 53% female and primarily non-Hispanic whites. Mean BMI was within the normal category from 1976 to 1987. From 1988 on, mean BMI fluctuated but increased overall. The BMI of healthy volunteers at the NIH CC appears to follow national trends as described by National Health and Nutrition Examination Survey data of increasing body weight during the past three decades followed by a recent plateau.

  4. Oxytocin does not improve performance of patients with schizophrenia and healthy volunteers in a facial emotion matching task.

    PubMed

    Horta de Macedo, Ligia R; Zuardi, Antonio Waldo; Machado-de-Sousa, João Paulo; Chagas, Marcos Hortes N; Hallak, Jaime E C

    2014-12-15

    The neuropeptide oxytocin improves the performance in facial emotion recognition tests in healthy volunteers and in individuals with schizophrenia. Different paradigms are used in emotion recognition tasks, engaging different neurobiological bases. To date, the effects of oxytocin in facial emotion matching tasks have not been studied. The objective of this study was to evaluate the effects of intranasal oxytocin in a facial emotion matching task in patients with schizophrenia and healthy volunteers. Twenty patients and 20 healthy volunteers received 48 IU intranasal oxytocin and placebo in a double-blind, randomized, placebo-controlled, within subjects design. Fifty minutes after treatment, subjects completed a facial emotion matching task and three control tests. Oxytocin failed to improve facial affect processing, in contrast with previous results. Possible explanations are the fact that we used a facial emotion matching paradigm instead of emotion labeling tasks and a higher dose of oxytocin than the one used in most similar studies.

  5. Survival of gentamicin-loaded carrier erythrocytes in healthy human volunteers.

    PubMed

    Eichler, H G; Rameis, H; Bauer, K; Korn, A; Bacher, S; Gasić, S

    1986-02-01

    Resealed erythrocytes are potential slow release carriers for drugs and enzymes. We have investigated carrier erythrocyte survival in human volunteers using gentamicin (G) as encapsulated cell marker; G was readily incorporated into red cells by hypo-osmotic dialysis (87% efficiency of incorporation) and did not exit from carrier cells in vitro. Six healthy young volunteers were injected with 59 +/- 7 ml carrier erythrocytes containing 56 +/- 13 mg G. G levels were measured in plasma and haemolysed whole blood by RIA. After an initial phase of cell loss (up to 4.5 h post-injection) the carrier erythrocytes survived in circulation with a half-life of 22 days, as was indicated by intracellular G concentration. G levels were detectable in plasma during the first 90 min after injection. This indicates haemolysis of some carrier cells. In conclusion, carrier erythrocytes appear to circulate longer than any other drug carrier under investigation and may well serve as innocuous slow release system. PMID:3084270

  6. The effect of titrated fentanyl on suppressed cough reflex in healthy adult volunteers.

    PubMed

    Kelly, H E; Shaw, G M; Brett, C N; Greenwood, F M; Huckabee, M L

    2016-05-01

    Cough suppression is part of the pharmacodynamic profile of opioids. We investigated the impact of clinical doses of fentanyl on suppressing the cough reflex. Thirteen volunteers received 2 μg.kg(-1) of fentanyl in a divided administration protocol. Three minutes after each administration and at 10 min intervals during washout, suppressed cough reflex testing with nebulised citric acid was performed and compared with fentanyl effect-site concentration. Mean (SD) citric acid concentration provoking cough increased from 0.5 (0.28) mol.l(-1) at baseline to 1.2 (0.50) mol.l(-1) after 2 μg.kg(-1) of fentanyl (p = 0.01). Mean (SD) fentanyl effect-site concentration after the final dose of fentanyl was 1.89 (0.05) ng.ml(-1) . A strong positive correlation was found between suppressed cough reflex thresholds and fentanyl effect-site concentrations during both fentanyl administration and washout phases of the study (r(2) = 0.79, p = 0.01). The mean (SD) length of time for return of suppressed cough response was 44.6 (18.8) min. Clinically relevant doses of fentanyl produced cough reflex suppression in healthy volunteers. PMID:26919658

  7. The effect of titrated fentanyl on suppressed cough reflex in healthy adult volunteers.

    PubMed

    Kelly, H E; Shaw, G M; Brett, C N; Greenwood, F M; Huckabee, M L

    2016-05-01

    Cough suppression is part of the pharmacodynamic profile of opioids. We investigated the impact of clinical doses of fentanyl on suppressing the cough reflex. Thirteen volunteers received 2 μg.kg(-1) of fentanyl in a divided administration protocol. Three minutes after each administration and at 10 min intervals during washout, suppressed cough reflex testing with nebulised citric acid was performed and compared with fentanyl effect-site concentration. Mean (SD) citric acid concentration provoking cough increased from 0.5 (0.28) mol.l(-1) at baseline to 1.2 (0.50) mol.l(-1) after 2 μg.kg(-1) of fentanyl (p = 0.01). Mean (SD) fentanyl effect-site concentration after the final dose of fentanyl was 1.89 (0.05) ng.ml(-1) . A strong positive correlation was found between suppressed cough reflex thresholds and fentanyl effect-site concentrations during both fentanyl administration and washout phases of the study (r(2) = 0.79, p = 0.01). The mean (SD) length of time for return of suppressed cough response was 44.6 (18.8) min. Clinically relevant doses of fentanyl produced cough reflex suppression in healthy volunteers.

  8. Separate and combined psychopharmacological effects of alprazolam and oxycodone in healthy volunteers

    PubMed Central

    Zacny, James P.; Paice, Judith A.; Coalson, Dennis W.

    2013-01-01

    Background There are epidemiological data indicating that medical and/or nonmedical use of prescription opioids oftentimes involves concurrent use of other substances. One of those substances is benzodiazepines. It would be of relevance to characterize the effects of an opioid and a benzodiazepine when taken together to determine if measures related to abuse liability-related effects and psychomotor performance impairment are increased compared to when the drugs are taken alone. Methods Twenty volunteers participated in a crossover, randomized, double-blind study in which they received placebo, 0.5 mg alprazolam, 10mg oxycodone, and 0.5 mg alprazolam combined with 10mg oxycodone, all p.o. Subjective, psychomotor, and physiological measures were assessed during each of the four sessions. Results Oxycodone by itself increased drug liking and “take again” ratings relative to placebo, but these ratings were not increased when oxycodone was taken with alprazolam, which by itself did not increase either of these ratings. The two drugs in combination produced stronger effects (larger in magnitude or longer lasting) than when either was taken alone on a number of measures, including psychomotor performance impairment. Conclusions In healthy volunteers, abuse liability-related subjective effects of oxycodone were not enhanced by alprazolam. There was enhanced behavioral toxicity when the drugs were taken together, and thus, this is of significant concern from a public safety standpoint. PMID:22365897

  9. Effect of an acidic beverage (Coca-Cola) on the pharmacokinetics of carbamazepine in healthy volunteers.

    PubMed

    Malhotra, S; Dixit, R K; Garg, S K

    2002-01-01

    The effect of an acidic beverage (Coca-Cola) on the pharmacokinetics of a single dose of carbamazepine was studied. In a two-way cross-over design with a 1 week washout period, 10 healthy volunteers were randomized to received 200 mg carbamazepine orally with 300 ml of Coca-Cola or water. Blood samples were collected at 0, 0.5, 1, 2, 3, 6, 9, 12, 24, 48 and 72 h after drug administration. Plasma carbamazepine levels were higher with Coca-Cola as compared to water. The AUC0-infinity and Cmax of carbamazepine were significantly enhanced after Coca-Cola while tmax was achieved earlier with Coca-Cola. The results of the study indicate that concomitant administration of Coca-Cola enhances the rate and extent of absorption of carbamazepine.

  10. A drug interaction study of ceftriaxone and frusemide in healthy volunteers.

    PubMed

    Korn, A; Eichler, H G; Gasic, S

    1986-05-01

    Ceftriaxone, a recently developed cephalosporin significantly reduced the diuretic activity of frusemide in rats. For this reason and because an interaction of unknown mechanism is well established between frusemide and some cephalosporins, we studied the interference of ceftriaxone with the diuretic effect of frusemide in healthy volunteers. Twelve subjects received frusemide (40 mg p.o.) or placebo in combination with ceftriaxone (2 g i.v.) or saline on 4 different days (cross-over, randomized, single-blind study). Urine was collected in small portions during 24 hours after medication and analyzed for volume, osmolality, Na+, K+, Cl- and creatinine concentration. Ceftriaxone had neither an effect on basal urinary output and electrolyte excretion nor on the specific diuretic action of frusemide.

  11. Effects of flumazenil on cholecystokinin-tetrapeptide-induced panic symptoms in healthy volunteers.

    PubMed

    Bradwejn, J; Koszycki, D; Couëtoux du Tertre, A; Paradis, M; Bourin, M

    1994-03-01

    The neuropeptide cholecystokinin-tetrapeptide (CCK-4) has potent anxiogenic action in human and animal subjects. On the basis of prior work which demonstrated that benzodiazepine (BZD) receptor agonists antagonized CCK-induced excitation of rat hippocampal neurons we studied whether BZD receptors mediated the anxiogenic effect of CCK-4. To examine this possibility we determined whether the BZD receptor antagonist flumazenil could antagonize the effects of CCK-4 (50 micrograms) in healthy volunteers. Thirty subjects (10 females; 20 males) were pretreated with flumazenil (2 mg in saline) or placebo (0.9% NaCl in water) 15 min prior to CCK-4 challenge in a randomized double-blind crossover design. Flumazenil had no impact on the behavioral and cardiovascular effects of CCK-4, suggesting that BZD receptors do not mediate the anxiogenic action of CCK-4. The influence of GABA and non-GABA-related mechanisms on response to CCK-4 remains to be considered.

  12. Dose ranging study of the effects of cholecystokinin in healthy volunteers.

    PubMed

    Bradwejn, J; Koszycki, D; Bourin, M

    1991-07-01

    The authors determined whether response to cholecystokinin-tetrapeptide (CCK-4) was dose-dependent. Healthy volunteers (n = 36) received double-blind injections of either 9 micrograms, 25 micrograms, or 50 micrograms of CCK-4 and placebo in a randomized sequence of injection. Significant dose-related differences were found for the number of symptoms, sum intensity of symptoms and the time until onset of symptoms, but not for the duration of symptoms. The incidence of panic attacks with CCK-4 was 11%, 17% and 47% for the 9 micrograms, 25 micrograms and 50 micrograms dose, respectively. None of the controls panicked with placebo injections. These results support the notion of a dose-dependent effect of CCK-4-induced panic symptoms. Implications of these findings in the neurobiology of panic attacks are discussed.

  13. RATIONALIZED AND COMPLEMENTARY FINDINGS OF SILYMARIN (MILK THISTLE) IN PAKISTANI HEALTHY VOLUNTEERS.

    PubMed

    Ashraf, Muhammad; Abid, Farah; Riffat, Sualeha; Bashir, Sajid; Iqbal, Javed; Sarfraz, Muhammad; Afzal, Attia; Zaheer, Muhammad

    2015-01-01

    The aim of the work was to examine the influence of gender on pharmacokinetics of silymarin; a basic constituent of medicinal herb "milk thistle" (Silybum marianum). The presented work is the extension of published work of Usman et al. (16). The comparative parallel design pharmacokinetic study was conducted in Pakistani healthy volunteers (male and female) receiving a single 200 mg oral dose of silymarin. Sixteen subjects (8 males and 8 females) were enrolled and completed the 12 h study. Blood screening was done on HPLC and the pharmacokinetic parameters were calculated by APO, 3.2 Ver. software using non-compartmental and two compartment model approaches. A significant difference (p < 0.05) was observed in almost all calculated pharmacokinetic parameters of silymarin in male and female. Clinically, the silymarin has been underestimated in the previous study. Gender based clinical investigations should be directed in the future on other flavono-lignans of 'milk thistle' as well.

  14. Objective markers of drug effects on brain function from recordings of scalp potential in healthy volunteers

    PubMed Central

    Boeijinga, Peter H.

    2002-01-01

    In order to stress the importance of P300 responses in drug development, we describe the spatiotemporal characteristics of this objective, evoked event-related potential. These brain activations reflect mnemonic function, in which limbic structures play a role. It is demonstrated that a pharmacological challenge concerning, for example, the cholinergic system in young healthy volunteers induces modifications in P300 reminiscent of the aging brain. We use this type of observation to build a model in which it can be verified whether the deterioration can be counteracted by treatment with “cognition-enhancing” drugs. If we accept the extrapolation of the pharmacological effects to symptomatology, scalp potential analysis offers an appropriate tool for the study of drug interactions in early proof-of-concept models. PMID:22033496

  15. Reproducibility of resting state spinal cord networks in healthy volunteers at 7 Tesla.

    PubMed

    Barry, Robert L; Rogers, Baxter P; Conrad, Benjamin N; Smith, Seth A; Gore, John C

    2016-06-01

    We recently reported our findings of resting state functional connectivity in the human spinal cord: in a cohort of healthy volunteers we observed robust functional connectivity between left and right ventral (motor) horns and between left and right dorsal (sensory) horns (Barry et al., 2014). Building upon these results, we now quantify the within-subject reproducibility of bilateral motor and sensory networks (intraclass correlation coefficient=0.54-0.56) and explore the impact of including frequencies up to 0.13Hz. Our results suggest that frequencies above 0.08Hz may enhance the detectability of these resting state networks, which would be beneficial for practical studies of spinal cord functional connectivity.

  16. Immunomodulatory consequences of oral administration of Lactobacillus rhamnosus strain GG in healthy volunteers.

    PubMed

    Schultz, Michael; Linde, Hans-Jörg; Lehn, Norbert; Zimmermann, Kurt; Grossmann, Johannes; Falk, Werner; Schölmerich, Jürgen

    2003-05-01

    Probiotic microorganisms, especially lactic acid bacteria, are effective in the treatment of infectious diarrhoeal diseases and experimental colitis. Although the mechanisms by which these organisms exert their anti-inflammatory effects are largely unknown, immunomodulating effects are suggested. The objective of this study was to examine the effect of a 5-week oral administration of Lactobacillus rhamnosus subspecies GG (Lb. GG) on the cellular immune response to intestinal microorganisms in ten healthy volunteers. Peripheral blood cells (PB) were stimulated with either 'self' or 'non-self' preparations of faecal samples and isolated Bacteroides fragilis group-organisms (Bfg) or Escherichia coli (Esch. coli), and pro- and anti-inflammatory cytokines (IL-10, IL-4, IL-6, IFN-gamma, TNF-alpha) were measured in the culture supernatant. CD4+ T-lymphocyte activation was determined by measurement of intracellular ATP following lysis of the cells. The activational response of CD4+ T-lymphocytes towards isolated and heat-inactivated intestinal organisms was increased after the probiotic treatment. Additionally, TNF-alpha, IL-6 and in part IFN-gamma cytokine secretion by PB cells following stimulation with whole stool preparations and single members of the flora was significantly decreased, whereas the IL-10 and in part IL-4 cytokine secretion was increased at the end of the study. In contrast, the activational response of CD4+ T-lymphocytes following stimulation with whole 'non-self' intestinal flora was higher than by 'self' intestinal flora, but both responses showed a trend towards a reduction at the end of the study. This study documents a direct effect by Lb. GG on the cellular immune system of healthy volunteers and offers a promising tool to investigate systemic immunomodulation due to oral administration of probiotic microorganisms.

  17. Dreaming under antidepressants: a systematic review on evidence in depressive patients and healthy volunteers.

    PubMed

    Tribl, Gotthard G; Wetter, Thomas C; Schredl, Michael

    2013-04-01

    Sleep related symptoms of depression include sleep fragmentation, early morning awakening, decreased rapid eye movement (REM) sleep latency, increased REM density, and more negative dream content. Most tricyclic antidepressants (ADs) increase total sleep time and decrease wake time after sleep onset, while many selective serotonin reuptake inhibitors (SSRIs) have an opposite effect. However, almost all ADs prolong REM sleep latency and reduce the amount of REM sleep. Case reports and research data indicate a strong effect of ADs on dream recall and dream content. We performed a systematic review (1950 to August 2010) about ADs impact on dreaming in depressive patients and healthy volunteers. Twenty-one clinical studies and 25 case reports were eligible for review and document a clear AD effect on dreaming. The major finding, both in depressed patients and in healthy volunteers, is a decrease of dream recall frequency (DRF) under ADs. This is a rather consistent effect in tricyclic ADs and phenelzine, less consistently documented also for SSRIs/serotonin norepinephrine reuptake inhibitors (SNRIs). Tricyclic ADs induce more positive dream emotions. Withdrawal from tricyclic ADs and from the monoamine oxidase inhibitors phenelzine and tranylcypromine may cause nightmares. Intake and even more withdrawal of SSRIs/SNRIs seem to intensify dreaming, which may be experienced in different ways; a potential to cause nightmares has to be taken into account. Though there are clear-cut pharmacological effects of ADs on DRF and dream content, publications have been surprisingly scarce during the past 60 years. There is evidence of a gap in neuropsychopharmacological research. AD effects on dreams should be recognized and may be used in treatment.

  18. Virtual Reality-Guided Motor Imagery Increases Corticomotor Excitability in Healthy Volunteers and Stroke Patients

    PubMed Central

    2016-01-01

    Objective To investigate the effects of using motor imagery (MI) in combination with a virtual reality (VR) program on healthy volunteers and stroke patients. In addition, this study investigated whether task variability within the VR-guided MI programs would influence corticomotor excitability. Methods The present study included 15 stroke patients and 15 healthy right-handed volunteers who were presented with four different conditions in a random order: rest, MI alone, VR-guided MI, and VR-guided MI with task variability. The corticomotor excitability of each participant was assessed before, during, and after each condition by measuring changes in the various parameters of motor-evoked potentials (MEPs) of the extensor carpi radials (ECR). Changes in intracortical inhibition (ICI) and intracortical facilitation (ICF) were calculated after each condition as percentages of inhibition (%INH) and facilitation (%FAC) at rest. Results In both groups, the increases in MEP amplitudes were greater during the two VR-guided MI conditions than during MI alone. Additionally, the reductions in ECR %INH in both groups were greater under the condition involving VR-guided MI with task variability than under that involving VR-guided MI with regular interval. Conclusion The corticomotor excitability elicited by MI using a VR avatar representation was greater than that elicited by MI with real body observations. Furthermore, the use of task variability in a VR program may enhance neural regeneration after stroke by reducing ICI. The present findings support the use of various VR programs as well as the concept of combining MI with VR programs for neurorehabilitation. PMID:27446778

  19. Comparative bioavailability study of two ibuprofen preparations after oral administration in healthy volunteers.

    PubMed

    Bienert, Agnieszka; Szkutnik-Fiedler, Danuta; Dyderski, Stanisław; Grześkowiak, Edmund; Drobnik, Leon; Wolc, Anna; Slawińiska, Urszula

    2006-01-01

    The bioavailability of a new ibuprofen (2-(p-isobutylphenyl)propionic acid, CAS 15687-27-1) preparation was compared with a reference preparation of the drug in 23 healthy male volunteers, aged between 19 and 27. A single dose of 400 mg was given orally in the fasted state, using a randomized two-way crossover study. A washout period of two weeks separated both treatment periods. Ibuprofen plasma levels were determined by means of a validated HPLC method (UV detector). Values of 154.48 +/- 53.27 microg x h/ml (95 % confidence interval CI: 133.50-177.03) for the test, and 140.86 +/- 44.82 microg x h/ml (95% CI: 122.53-159.16) for the reference preparation AUC(0-infinity) demonstrate a nearly identical extent of drug absorption. Maximum plasma concentrations Cmax of 39.53 +/- 7.11 microg/ml (95 % CI: 35.97-41.78) and 37.71 +/- 8.67 microg/ml (95% CI: 33.37-40.46) achieved for the test and reference preparations did not differ significantly. AUC(0-infinity) and Cmax ratios (90% CI) were within the 80-125% interval required for bioequivalence as stipulated in the current international regulations of the European Agency for the Evalution of Medicinal Products and the Food and Drug Administration. Therefore it is concluded that the new ibuprofen preparation is therapeutically equivalent to the reference preparation for both, the extent and the rate of absorption, after single dose administration in healthy volunteers.

  20. Buccal acetaminophen provides fast analgesia: two randomized clinical trials in healthy volunteers

    PubMed Central

    Pickering, Gisèle; Macian, Nicolas; Libert, Frédéric; Cardot, J Michel; Coissard, Séverine; Perovitch, Philippe; Maury, Marc; Dubray, Claude

    2014-01-01

    Background Acetaminophen (APAP) by oral or intravenous (iv) routes is used for mild to moderate pain but may take time to be effective. When fast relief is required and/or oral or iv routes are not available because of the patient’s condition, the transmucosal route may be an alternative. Methodology A new transmucosal/buccal (b) pharmaceutical form of APAP dissolved in 50% wt alcohol is compared with other routes of administration. Two consecutive randomized, crossover, double-blind clinical trials (CT1: NCT00982215 and CT2: NCT01206985) included 16 healthy volunteers. CT1 compared the pharmacology of 250 mg bAPAP with 1 g iv APAP. CT2 compared the pharmacodynamics of 125 mg bAPAP with 1 g iv and 125 mg sublingual (s) APAP. Mechanical pain thresholds are recorded in response to mechanical stimuli applied on the forearm several times during 120 minutes. The objective is to compare the time of onset of antinociception and the antinociception (area under the curve) between the routes of administration with analysis of variance (significance P<0.05). Results bAPAP has a faster time of antinociception onset (15 minutes, P<0.01) and greater antinociception at 50 minutes (P<0.01, CT1) and 30 minutes (P<0.01, CT2) than ivAPAP and sAPAP. All routes are similar after 50 minutes. Conclusion bAPAP has a faster antinociceptive action in healthy volunteers. This attractive alternative to other routes would be useful in situations where oral or iv routes are not available. This finding must now be confirmed in patients suffering from acute pain of mild and moderate intensity. PMID:25302017

  1. Hyperoxia Improves Hemodynamic Status During Head-up Tilt Testing in Healthy Volunteers

    PubMed Central

    Fromonot, Julien; Chaumet, Guillaume; Gavarry, Olivier; Rostain, Jean-Claude; Lucciano, Michel; Joulia, Fabrice; Brignole, Michele; Deharo, Jean-Claude; Guieu, Regis; Boussuges, Alain

    2016-01-01

    Abstract Head-up tilt test is useful for exploring neurally mediated syncope. Adenosine is an ATP derivative implicated in cardiovascular disturbances that occur during head-up tilt test. The aim of the present study was to investigate the impact of hyperoxia on adenosine plasma level and on hemodynamic changes induced by head-up tilt testing. Seventeen healthy male volunteers (mean age 35 ± 11 years) were included in the study. The experiment consisted of 2 head-up tilt tests, 1 session with subjects breathing, through a mask, medical air (FiO2 = 21%) and 1 session with administration of pure oxygen (FiO2 = 100%) in double-blind manner. Investigations included continuous monitoring of hemodynamic data and measurement of plasma adenosine levels. No presyncope or syncope was found in 15 of the 17 volunteers. In these subjects, a slight decrease in systolic blood pressure was recorded during orthostatic stress performed under medical air exposure. In contrast, hyperoxia led to increased systolic blood pressure during orthostatic stress when compared with medical air. Furthermore, mean adenosine plasma levels decreased during hyperoxic exposure before (0.31 ± 0.08 μM) and during head-up tilt test (0.33 ± 0.09 μM) when compared with baseline (0.6 ± 0.1 μM). Adenosine plasma level was unchanged during medical air exposure at rest (0.6 ± 0.1 μM), and slightly decreased during orthostatic stress. In 2 volunteers, the head-up tilt test induced a loss of consciousness when breathing air. In these subjects, adenosine plasma level increased during orthostatic stress. In contrast, during hyperoxic exposure, the head-up tilt test did not induce presyncope or syncope. In these 2 volunteers, biological study demonstrated a decrease in adenosine plasma level at both baseline and during orthostatic stress for hyperoxic exposure compared with medical air. These results suggest that hyperoxia was able to increase blood pressure during head

  2. The Association between Baseline Subjective Anxiety Rating and Changes in Cardiac Autonomic Nervous Activity in Response to Tryptophan Depletion in Healthy Volunteers.

    PubMed

    Hsiao, Chih Yin; Tsai, Hsin Chun; Chi, Mei Hung; Chen, Kao Chin; Chen, Po See; Lee, I Hui; Yeh, Tzung Lieh; Yang, Yen Kuang

    2016-05-01

    The aim of this study was to investigate the influence of serotonin on anxiety and autonomic nervous system (ANS) function; the correlation between subjective anxiety rating and changes of ANS function following tryptophan depletion (TD) in healthy volunteers was examined. Twenty-eight healthy participants, consisting of 15 females and 13 males, with an average age of 33.3 years, were recruited.Baseline Chinese Symptom Checklist-90-Revised and ANS function measurements were taken. TD was carried out on the testing day, and participants provided blood samples right before and 5 hours after TD. ANS function, somatic symptoms, and Visual Analogue Scales (VASs) were determined after TD. Wilcoxon signed rank test and Spearman ρ correlation were adapted for analyses of the results.The TD procedure reduced total and free plasma tryptophan effectively. After TD, the sympathetic nervous activity increased and parasympathetic nervous activity decreased. Baseline anxiety ratings positively correlated with post-TD changes in sympathetic nervous activity, VAS ratings, and physical symptoms. However, a negative correlation with post-TD changes in parasympathetic nervous activity was found.The change in ANS function after TD was associated with the severity of anxiety in healthy volunteers. This supports the fact that the effect of anxiety on heart rate variability is related to serotonin vulnerability. Furthermore, it also shows that the subjective anxiety rating has a biological basis related to serotonin.

  3. The Association between Baseline Subjective Anxiety Rating and Changes in Cardiac Autonomic Nervous Activity in Response to Tryptophan Depletion in Healthy Volunteers.

    PubMed

    Hsiao, Chih Yin; Tsai, Hsin Chun; Chi, Mei Hung; Chen, Kao Chin; Chen, Po See; Lee, I Hui; Yeh, Tzung Lieh; Yang, Yen Kuang

    2016-05-01

    The aim of this study was to investigate the influence of serotonin on anxiety and autonomic nervous system (ANS) function; the correlation between subjective anxiety rating and changes of ANS function following tryptophan depletion (TD) in healthy volunteers was examined. Twenty-eight healthy participants, consisting of 15 females and 13 males, with an average age of 33.3 years, were recruited.Baseline Chinese Symptom Checklist-90-Revised and ANS function measurements were taken. TD was carried out on the testing day, and participants provided blood samples right before and 5 hours after TD. ANS function, somatic symptoms, and Visual Analogue Scales (VASs) were determined after TD. Wilcoxon signed rank test and Spearman ρ correlation were adapted for analyses of the results.The TD procedure reduced total and free plasma tryptophan effectively. After TD, the sympathetic nervous activity increased and parasympathetic nervous activity decreased. Baseline anxiety ratings positively correlated with post-TD changes in sympathetic nervous activity, VAS ratings, and physical symptoms. However, a negative correlation with post-TD changes in parasympathetic nervous activity was found.The change in ANS function after TD was associated with the severity of anxiety in healthy volunteers. This supports the fact that the effect of anxiety on heart rate variability is related to serotonin vulnerability. Furthermore, it also shows that the subjective anxiety rating has a biological basis related to serotonin. PMID:27175645

  4. The Association between Baseline Subjective Anxiety Rating and Changes in Cardiac Autonomic Nervous Activity in Response to Tryptophan Depletion in Healthy Volunteers

    PubMed Central

    Hsiao, Chih Yin; Tsai, Hsin Chun; Chi, Mei Hung; Chen, Kao Chin; Chen, Po See; Lee, I Hui; Yeh, Tzung Lieh; Yang, Yen Kuang

    2016-01-01

    Abstract The aim of this study was to investigate the influence of serotonin on anxiety and autonomic nervous system (ANS) function; the correlation between subjective anxiety rating and changes of ANS function following tryptophan depletion (TD) in healthy volunteers was examined. Twenty-eight healthy participants, consisting of 15 females and 13 males, with an average age of 33.3 years, were recruited. Baseline Chinese Symptom Checklist-90-Revised and ANS function measurements were taken. TD was carried out on the testing day, and participants provided blood samples right before and 5 hours after TD. ANS function, somatic symptoms, and Visual Analogue Scales (VASs) were determined after TD. Wilcoxon signed rank test and Spearman ρ correlation were adapted for analyses of the results. The TD procedure reduced total and free plasma tryptophan effectively. After TD, the sympathetic nervous activity increased and parasympathetic nervous activity decreased. Baseline anxiety ratings positively correlated with post-TD changes in sympathetic nervous activity, VAS ratings, and physical symptoms. However, a negative correlation with post-TD changes in parasympathetic nervous activity was found. The change in ANS function after TD was associated with the severity of anxiety in healthy volunteers. This supports the fact that the effect of anxiety on heart rate variability is related to serotonin vulnerability. Furthermore, it also shows that the subjective anxiety rating has a biological basis related to serotonin. PMID:27175645

  5. Effect of intermittent administration of omeprazole on serum pepsinogens in duodenal ulcer patients and healthy volunteers.

    PubMed

    Biemond, I; Crobach, L F; Jansen, J B; Lamers, C B

    1990-04-01

    1. Omeprazole, a substituted benzimidazole inhibitor of the gastric H+/K(+)-APT-ase, was administered orally at a dose of 20 mg in the morning of 3 consecutive days, followed by a period of 4 days without medication, and this intermittent dosage regimen was continued for 4 weeks. 2. During intermittent administration of omeprazole to 10 patients with duodenal ulcer disease and 10 healthy volunteers concentrations of serum pepsinogen A and serum pepsinogen C were monitored by sensitive and specific radioimmunoassays to study whether the effect of this treatment on serum pepsinogens is different between patients and normal subjects and to evaluate whether serum pepsinogen levels can be used to assess compliance with therapy. 3. Administration of omeprazole for 3 days induced significant increases in pepsinogen A and pepsinogen C serum concentrations, which rapidly fell after stopping the omeprazole intake. The pattern of serum pepsinogens after stopping the drug was different for duodenal ulcer patients and normal subjects. Both pepsinogens were intra-individually related in both patients and healthy subjects when compared during the first and last 3-day course with omeprazole, but in duodenal ulcer patients both pepsinogens tended to be higher in the last treatment course, while the opposite was found in the normal subjects. 4. The present study confirms that serum pepsinogen concentrations are higher in duodenal ulcer patients than in normal subjects, but also shows for the first time that serum pepsinogens in the patients respond differently upon stimulation with omeprazole.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2328194

  6. Bayesian adaptive designs in single ascending dose trials in healthy volunteers

    PubMed Central

    Guédé, David; Reigner, Bruno; Vandenhende, Francois; Derks, Mike; Beyer, Ulrich; Jordan, Paul; Worth, Eric; Diack, Cheikh; Frey, Nicolas; Peck, Richard

    2014-01-01

    Aim Recent publications indicate a strong interest in applying Bayesian adaptive designs in first time in humans (FTIH) studies outside of oncology. The objective of the present work was to assess the performance of a new approach that includes Bayesian adaptive design in single ascending dose (SAD) trials conducted in healthy volunteers, in comparison with a more traditional approach. Methods A trial simulation approach was used and seven different scenarios of dose–response were tested. Results The new approach provided less biased estimates of maximum tolerated dose (MTD). In all scenarios, the number of subjects needed to define a MTD was lower with the new approach than with the traditional approach. With respect to duration of the trials, the two approaches were comparable. In all scenarios, the number of subjects exposed to a dose greater than the actual MTD was lower with the new approach than with the traditional approach. Conclusions The new approach with Bayesian adaptive design shows a very good performance in the estimation of MTD and in reducing the total number of healthy subjects. It also reduces the number of subjects exposed to doses greater than the actual MTD. PMID:24528176

  7. Effect of disulfiram on the platelet function and fibrinolysis in healthy volunteers.

    PubMed

    Gleerup, G; Boström, S; Hansson, G; Teger-Nilsson, A C; Sjöquist, P O; Winther, K

    1990-01-01

    Disulfiram was studied for platelet and fibrinolytic activity in 12 healthy volunteers of both sexes (age 23-75 years). Placebo was given for 7 days, followed by disulfiram, 800 mg for 2 days and 400 mg for an additional 12 days. Finally, there was another placebo period of 14 days. With the exception of an initial platelet activation on day 2, no significant effects were found on the platelet variables studied: platelet aggregation with collagen, ADP and adrenaline, beta-thromboglobulin and platelet factor 4. Treatment for 14 days with disulfiram resulted in a decreased euglobulin clot lysis time: from 421 +/- 82 to 246 +/- 41 min (p less than 0.01). After an initial increase, plasminogen activator inhibitor activity was slightly decreased on disulfiram, from 8.4 +/- 1.6 on placebo to 6.0 +/- 1.2 U/ml (p less than 0.05) after 14 days of treatment. Plasminogen, fibrinogen and alpha 2-antiplasmin were unchanged. It is concluded that disulfiram can increase fibrinolytic activity in healthy subjects.

  8. First clinical experience with TRV027: pharmacokinetics and pharmacodynamics in healthy volunteers.

    PubMed

    Soergel, David G; Subach, Ruth Ann; Cowan, Conrad L; Violin, Jonathan D; Lark, Michael W

    2013-09-01

    TRV027 is a novel β-arrestin biased peptide ligand of the angiotensin II type 1 receptor (AT1R). The compound antagonizes G protein coupling while simultaneously stimulating β-arrestin-mediated signaling. In preclinical studies, TRV027 reversibly reduced blood pressure while preserving renal function in a dog tachypaced heart failure model and stimulating cardiomyocyte contractility in vitro. This profile suggests that TRV027 may have unique benefits in acute heart failure, a condition associated with renin-angiotensin system activation. A first-time-in-human study was conducted with ascending doses of TRV027 to explore its tolerability, pharmacokinetics and pharmacodynamics in healthy volunteers. Subjects' salt intake was restricted to stimulate RAS activation. In this study TRV027 was safe and well tolerated with a short-half-life (ranging between 2.4 and 13.2 minutes) and dose-proportional increases in systemic exposure. Consistent with the pre-clinical findings, TRV027 reduced blood pressure to a greater degree in subjects with RAS activation, measured as elevated plasma renin activity, than in those with normal PRA levels. This study in sodium-restricted healthy subjects suggests that TRV027 will successfully target a core mechanism of acute heart failure pathophysiology. Further clinical studies with TRV027 in patients with heart failure are underway.

  9. Electrophysiological and neuropsychological effects of a central alpha 2-antagonist atipamezole in healthy volunteers.

    PubMed

    Mervaala, E; Alhainen, K; Helkala, E L; Partanen, J; Jousmäki, V; Väyrynen, M; Heinonen, E; Riekkinen, P

    1993-05-31

    We studied the electrophysiological and neuropsychological effects of acute modulation of central noradrenergic (NA) transmission using a specific alpha 2-antagonist atipamezole (ATI) in sic healthy volunteers. ATI had effects on resting EEG, auditory event-related potentials and neuropsychological tests. Quantitative EEG revealed increased total power in frontal, parietal and temporo-occipital areas without significant changes in the mean or peak frequencies. Event-related potentials showed no effects on the active attention-related processing negativity or the passive mismatch negativity, but frontally recorded mean amplitude of target-P300 was decreased. Neuropsychological tests after ATI revealed improvement in Digit Span, more errors in Word Recognition task, and no effects on Moss spatial recognition task. In healthy subjects with intact NA systems and without any attention deficit, ATI produced evident NA overactivity. ATI decreased the spontaneous thalamocortical oscillation of EEG and improved focused attention (Digit Span). It impaired, however, more divided attention (decreased mean P300 amplitude, increased errors in Word Recognition). PMID:8101086

  10. Pharmacokinetics and safety of JTE-522, a novel selective cyclooxygenase-2 inhibitor, in healthy male volunteers

    PubMed Central

    Ikeda, Yasuhiko; Umemura, Kazuo; Kondo, Kazunao; Nakashima, Mitsuyoshi; Kobayashi, Takuo; Takahashi, Mitsuru

    2002-01-01

    Aims The pharmacokinetics and safety profile of JTE-522, 4-(4-cyclohexyl-2 methyloxazol-5-yl)-2-fluorobenzensulphonamide, a novel selective cyclooxygenase-2 inhibitor were investigated in healthy male volunteers. Methods Initially, as a pilot study, five groups of two subjects were given oral doses of 3–100 mg of JTE-522. After safety assessment, subjects were given 150 and 200 mg of JTE-522. The effect of food-intake on the pharmacokinetics of JTE-522 at a dose of 150 mg was examined. In the multiple-dose study, subjects were given 150 mg of JTE-522 once a day for 7 days. Concentrations of unchanged JTE-522 in plasma, blood and urine were determined by high performance liquid chromatography (h.p.l.c.). Concentrations of metabolites were estimated with h.p.l.c. chromatograms and calibration curves for quantification of unchanged JTE-522. Results In the course of this study, no serious abnormality attributable to the test drug was observed, suggesting that JTE-522 was well tolerated in healthy subjects. In a single-dose study, the concentrations of JTE-522 in blood were much higher than the corresponding concentrations in plasma. JTE-522 was readily distributed to blood cells and percentage distribution into blood cells was more than 99.0%. However, the values of Cmax in blood at doses of 100, 150, 200 mg JTE-522 were 15241, 20445 ± 3918 (16333–24556), 20965 ± 3260 (17544–24386) ng ml−1, respectively. These findings suggest that JTE-522 has a high affinity for blood cells and the distribution into blood cells is limited at the higher doses of over 100 mg. In a multiple dose study, pharmacokinetic parameters including t1/2 and AUC after the fourth administration were comparable with that of the seventh administration. Thus, these findings suggest the absence of accumulation on the multiple-dosing of JTE-522. Conclusions These results indicate that JTE-522 has an acceptable pharmacokinetic profile for clinical use without any serious adverse events as we

  11. Substantial Effect of Efavirenz Monotherapy on Bilirubin Levels in Healthy Volunteers

    PubMed Central

    Metzger, Ingrid F.; Quigg, Troy C.; Epstein, Noam; Aregbe, Abdulateef O.; Thong, Nancy; Callaghan, John T.; Flockhart, David A.; Nguyen, Anne T.; Stevens, Colleen K.; Gupta, Samir K.; Desta, Zeruesenay

    2014-01-01

    Background Efavirenz exhibits multiple interactions with drug-metabolizing enzymes and transporters, and for this reason efavirenz-based HIV therapy is associated with altered pharmacokinetics of coadministered drugs. Probably by the same mechanism, efavirenz-based HIV therapy affects the disposition of endogenous compounds, but this effect is difficult to directly link with efavirenz because it is used in combination with other drugs. Objectives To explore the effect of efavirenz monotherapy on biochemical laboratory values in a clinical trial of healthy volunteers. Methods Men and women (aged 18–49 years) with body mass index ≤32 who were assessed to be healthy based on medical history, physical examination, and standard laboratory screening received a single (600 mg) and multiple doses (600 mg/d for 17 days) of efavirenz orally. This trial was designed to determine the pharmacokinetics and drug interactions of efavirenz. As part of this study, analysis of serum chemistries that were measured at study entry (screening) and 1 week after completion of the multiple dose study (exit) is reported. Results Data from 60 subjects who fully completed and 13 subjects who partially completed the study are presented. Total bilirubin was substantially reduced at exit (by ~30%, with large intersubject variability) compared with screening values (P < 0.0001). The percent changes were in part explained by the intersubject differences in baseline total bilirubin because there was a significant correlation between baseline (screening) values and percent change at exit (r = 0.50; P < 0.0001). Hemoglobin and absolute neutropenia were also substantially decreased at exit compared with screening, but this may be due to intensive blood sampling rather than direct effect of efavirenz on these parameters. No significant correlation was found between percent change in hemoglobin versus percent change in bilirubin, indicating the effect of efavirenz on bilirubin is independent of its

  12. Altruism, personal benefit, and anxieties: a phenomenological study of healthy volunteers' experiences in a placebo‐controlled trial of duloxetine

    PubMed Central

    Kwakye, Isaac N.; Garner, Matthew; Baldwin, David S.; Bamford, Susan; Pinkney, Verity

    2016-01-01

    Objective The objective of this study was to develop an in‐depth understanding of healthy volunteers' experiences of mental health trials. Methods A qualitative study was nested within a healthy volunteer placebo‐controlled trial of duloxetine, a psychotropic drug used for treating patients with major depression and generalized anxiety disorder. Eight participants were interviewed, and data were analyzed using interpretative phenomenological analysis. Results Interviewees described volunteering for the trial because they were interested in research, wanted the monetary incentive, wanted to help researchers, and wanted to be part of something. On entering the trial, participants considered the possible risks and described feeling anxious, excited, and determined; they had some clear expectations and some loosely held hopes about what would happen. During the trial, participants were curious about whether they were taking duloxetine or placebo, self‐monitored their bodies' reactions, and guessed which treatment they received. On being un‐blinded to treatment allocation after completing the trial, some participants' guesses were confirmed, but others were surprised, and a few were disappointed. Conclusions Small changes to advertising/consent materials to reflect volunteers' motivations could improve recruitment rates to similar trials; “active” placebos might be particularly useful for maintaining blinding in healthy volunteer trials; and sensitive procedures are needed for un‐blinding participants to treatment allocation. © 2016 The Authors. Human Psychopharmacology: Clinical and Experimental published by John Wiley & Sons, Ltd. PMID:27378326

  13. Cervical spine segmental vertebral motion in healthy volunteers feigning restriction of neck flexion and extension.

    PubMed

    Puglisi, Filadelfio; Strimpakos, Nikolaos; Papathanasiou, Matthildi; Kapreli, Eleni; Bonelli, Aurelio; Sgambetterra, Sergio; Ferrari, Robert

    2007-09-01

    The purpose of this study was to obtain comparative data concerning the percentage contribution of segmental cervical vertebral motion to the cervical range of motion (ROM) in healthy volunteers under two conditions: (1) normal, voluntary neck flexion and extension and (2) feigned restriction of neck flexion and extension. Each healthy subject's angular motion over forward cervical flexion and extension was measured first by X-ray analysis during normal, voluntary motion. Then the subjects were asked to pretend that they had a 50% restricted neck range due to pain or stiffness and thus to move in both flexion and extension only as far as about 50% of their normal range. A total of 26 healthy subjects (ten males and sixteen females, age 28.7+/-7.7 years) participated. The total angular motion from C2 to C7 was normal in the unrestricted condition and was significantly reduced in the feigned restriction condition (p<0.001). The percentage contribution of each of the functional units C2-C3 to C6-C7 to this rotation was different between the normal unrestricted and the feigned restricted conditions. In the feigned restricted neck flexion and extension, a shift occurred in the pattern of how each segment contributes to the total angular range. A greater percentage contribution was made by C2-C3 and C3-C4 than under normal conditions (P<0.01), and the percentage contribution to total rotation made by C6-C7 became much less under the feigned restricted movements than under normal, unrestricted neck range (p<0.001). Thus, simulated or feigned restricted neck ROM affects the percentage contribution of the functional units C2-C3 to C6-C7 by showing a higher percentage contribution of the upper cervical segments and less contribution to the angular rotation by the lowest cervical segment. Feigners of restricted neck range thus produce a pattern different from nonfeigning subjects.

  14. (3)He MRI in healthy volunteers: preliminary correlation with smoking history and lung volumes.

    PubMed

    Guenther, D; Eberle, B; Hast, J; Lill, J; Markstaller, K; Puderbach, M; Schreiber, W G; Hanisch, G; Heussel, C P; Surkau, R; Grossmann, T; Weiler, N; Thelen, M; Kauczor, H U

    2000-06-01

    MRI with hyperpolarized helium-3 ((3)He) provides high-resolution imaging of ventilated airspaces. The first aim of this (3)He-study was to compare observations of localized signal defects in healthy smokers and non-smokers. A second aim was to describe relationships between parameters of lung function, volume of inspired (3)He and signal-to-noise ratio. With Ethics Committee approval and informed consent, 12 healthy volunteers (seven smokers and five non-smokers) were studied. Imaging was performed in a 1.5 T scanner using a two-dimensional FLASH sequence at 30V transmitter amplitude (TR/TE/alpha = 11 ms/4.2 ms/<10 degrees ). Known amounts of (3)He were inhaled from a microprocessor-controlled delivery device and imaged during single breath-holds. Images were evaluated visually, and scored using a prospectively defined 'defect-index'. Signal-to-noise ratio of the images were correlated with localization, (3)He volumes and static lung volumes. Due to poor image quality studies of two smokers were not eligible for the evaluation. Smokers differed from non-smokers in total number and size of defects: the 'defect-index' of smokers ranged between 0.8 and 6.0 (median = 1.1), that of non-smokers between 0.1 and 0.8 (median = 0.4). Intraindividually, an anteroposterior gradient of signal-to-noise ratio was apparent. Signal-to-noise ratio correlated with the estimated amount of hyperpolarization administered (r = 0. 77), but not with static lung volumes. We conclude that (3)He MRI is a sensitive measure to detect regional abnormalities in the distribution of ventilation in clinically healthy persons with normal pulmonary function tests.

  15. Metabolic effects of a diet with inulin-enriched pasta in healthy young volunteers.

    PubMed

    Russo, F; Riezzo, G; Chiloiro, M; De Michele, G; Chimienti, G; Marconi, E; D'Attoma, B; Linsalata, M; Clemente, C

    2010-01-01

    Different lines of evidence suggest that higher intake of fiber may somehow protect against metabolic syndrome. The prebiotic inulin has widely been studied in relation to its putative beneficial effects on lipid and glucose metabolism. Therefore, adding inulin to diet may be a suitable strategy to prevent metabolic syndrome. Aim of the present study was to evaluate the effects of the daily consumption of inulin-enriched pasta on lipid and glucose metabolism as well as on gastrointestinal motility in young healthy subjects. Methods. Twenty-two healthy young male volunteers entered a randomized double blind cross-over study consisting of a 2-weeks a run-in period, two 5-weeks study periods (11% inulin-enriched or control pasta), and an 8-weeks wash-out period in between. Serum lipid and glucose concentrations were evaluated by routine biochemical analyses. Gastric emptying time and electrical activity were non-invasively evaluated by ultrasound and electrogastrography. Data were analyzed by Friedman Repeated Measures ANOVA test. Results. Significant differences among baseline and the treatment group were found for HDL-cholesterol (p=0.004), total cholesterol/HDL-cholesterol ratio (p=0.006), triglycerides (p=0.04), fasting glucose level (p=0.044), fructosamine (p=0.0478), HbA1c (p=0.04), and homeostatic model assessment (HOMA-IR) (p=0.045). The gastric emptying, expressed as final emptying time, was found significantly delayed in the group that assumed inulin-enriched pasta (p=0.008). Conclusions. Inulin-enriched pasta improved lipidic and glicidic metabolism as well as the insulin resistance in healthy young subjects. In addition, it delayed the gastric emptying time which may represent the physiological counterpart of its metabolic effects.

  16. Study on Yang-Xu Using Body Constitution Questionnaire and Blood Variables in Healthy Volunteers

    PubMed Central

    Chen, Hong-Jhang; Lin, Yii-Jeng; Wu, Pei-Chen; Hsu, Wei-Hsiang; Hu, Wan-Chung; Wu, Trong-Neng; Chen, Fang-Pey; Lin, Yun-Lian

    2016-01-01

    Traditional Chinese medicine (TCM) formulates treatment according to body constitution (BC) differentiation. Different constitutions have specific metabolic characteristics and different susceptibility to certain diseases. This study aimed to assess the Yang-Xu constitution using a body constitution questionnaire (BCQ) and clinical blood variables. A BCQ was employed to assess the clinical manifestation of Yang-Xu. The logistic regression model was conducted to explore the relationship between BC scores and biomarkers. Leave-one-out cross-validation (LOOCV) and K-fold cross-validation were performed to evaluate the accuracy of a predictive model in practice. Decision trees (DTs) were conducted to determine the possible relationships between blood biomarkers and BC scores. According to the BCQ analysis, 49% participants without any BC were classified as healthy subjects. Among them, 130 samples were selected for further analysis and divided into two groups. One group comprised healthy subjects without any BC (68%), while subjects of the other group, named as the sub-healthy group, had three BCs (32%). Six biomarkers, CRE, TSH, HB, MONO, RBC, and LH, were found to have the greatest impact on BCQ outcomes in Yang-Xu subjects. This study indicated significant biochemical differences in Yang-Xu subjects, which may provide a connection between blood variables and the Yang-Xu BC. PMID:27340421

  17. Study on Yang-Xu Using Body Constitution Questionnaire and Blood Variables in Healthy Volunteers.

    PubMed

    Chen, Hong-Jhang; Lin, Yii-Jeng; Wu, Pei-Chen; Hsu, Wei-Hsiang; Hu, Wan-Chung; Wu, Trong-Neng; Chen, Fang-Pey; Lin, Yun-Lian

    2016-01-01

    Traditional Chinese medicine (TCM) formulates treatment according to body constitution (BC) differentiation. Different constitutions have specific metabolic characteristics and different susceptibility to certain diseases. This study aimed to assess the Yang-Xu constitution using a body constitution questionnaire (BCQ) and clinical blood variables. A BCQ was employed to assess the clinical manifestation of Yang-Xu. The logistic regression model was conducted to explore the relationship between BC scores and biomarkers. Leave-one-out cross-validation (LOOCV) and K-fold cross-validation were performed to evaluate the accuracy of a predictive model in practice. Decision trees (DTs) were conducted to determine the possible relationships between blood biomarkers and BC scores. According to the BCQ analysis, 49% participants without any BC were classified as healthy subjects. Among them, 130 samples were selected for further analysis and divided into two groups. One group comprised healthy subjects without any BC (68%), while subjects of the other group, named as the sub-healthy group, had three BCs (32%). Six biomarkers, CRE, TSH, HB, MONO, RBC, and LH, were found to have the greatest impact on BCQ outcomes in Yang-Xu subjects. This study indicated significant biochemical differences in Yang-Xu subjects, which may provide a connection between blood variables and the Yang-Xu BC. PMID:27340421

  18. A Natural Electromagnetic Fields Effect on Healthy Volunteers During Long-Term Experiment with Isolation

    NASA Astrophysics Data System (ADS)

    Gurfinkel, Yury I.; Mikhailov, Valery M.; Ushakov, Boris B.

    2008-06-01

    There were investigated four healthy volunteers at the age of 37, 40, 41 and 48 during the baseline 240-d isolation period starting from July 3, 1999 in the frame of SFINCSS-99 - "SIMULATION OF FLIGHT OF INTERNATIONAL CREW ON SPACE STATION". Before a starting of experiment with long-term isolation were carried out measurements of magnetic properties of module and sleeping places. With the regularity of 3 times a week each subject made records of no less then 3 video episodes with the total length of one minute minimum at the same time between 1 and 2 p.m. Applying vital non-invasive computer capillaroscopy of nailbed has allowed quantitatively estimating a capillary blood velocity (CBV). The microcirculation parameters obtained during experiment were compared to local indexes of geomagnetic activity. About 1500 episodes were recorded on laser disks and analyzed. Parameters of microcirculation were compared with other physiological parameters monitored in the experiment. CBV investigation during the most intensive magnetic storm for the period of isolation (A-index- 44) show, that CBV at all volunteers was considerably slowed down. The greatest delay of blood flow velocity revealed at the subject which the factor of shielding of a constant magnetic field at the level of the sleeping berth has made 2,0. CBV at the subject has made 498 ± 46 μm/s with (- 65,8 % from base line). Least delay of a CBV is revealed at the subject which the factor of shielding of a constant magnetic field at the level of the sleeping berth has made 3, 15 (-12 % from base line).

  19. Reproducibility of the heat/capsaicin skin sensitization model in healthy volunteers

    PubMed Central

    Cavallone, Laura F; Frey, Karen; Montana, Michael C; Joyal, Jeremy; Regina, Karen J; Petersen, Karin L; Gereau, Robert W

    2013-01-01

    Introduction Heat/capsaicin skin sensitization is a well-characterized human experimental model to induce hyperalgesia and allodynia. Using this model, gabapentin, among other drugs, was shown to significantly reduce cutaneous hyperalgesia compared to placebo. Since the larger thermal probes used in the original studies to produce heat sensitization are now commercially unavailable, we decided to assess whether previous findings could be replicated with a currently available smaller probe (heated area 9 cm2 versus 12.5–15.7 cm2). Study design and methods After Institutional Review Board approval, 15 adult healthy volunteers participated in two study sessions, scheduled 1 week apart (Part A). In both sessions, subjects were exposed to the heat/capsaicin cutaneous sensitization model. Areas of hypersensitivity to brush stroke and von Frey (VF) filament stimulation were measured at baseline and after rekindling of skin sensitization. Another group of 15 volunteers was exposed to an identical schedule and set of sensitization procedures, but, in each session, received either gabapentin or placebo (Part B). Results Unlike previous reports, a similar reduction of areas of hyperalgesia was observed in all groups/sessions. Fading of areas of hyperalgesia over time was observed in Part A. In Part B, there was no difference in area reduction after gabapentin compared to placebo. Conclusion When using smaller thermal probes than originally proposed, modifications of other parameters of sensitization and/or rekindling process may be needed to allow the heat/capsaicin sensitization protocol to be used as initially intended. Standardization and validation of experimental pain models is critical to the advancement of translational pain research. PMID:24232380

  20. Breath isoprene concentrations in persons undergoing general anesthesia and in healthy volunteers.

    PubMed

    Hornuss, Cyrill; Zagler, Armin; Dolch, Michael E; Wiepcke, Dirk; Praun, Siegfried; Boulesteix, Anne-Laure; Weis, Florian; Apfel, Christian C; Schelling, Gustav

    2012-12-01

    Human breath contains an abundance of volatile organic compounds (VOCs). Analysis of breath VOC may be used for diagnosis of various diseases or for on-line monitoring in anesthesia and intensive care. However, VOC concentrations largely depend on the breath sampling method and have a large inter-individual variability. For the development of breath tests, the influence of breath sampling methods and study subject characteristics on VOC concentrations has to be known. Therefore, we investigated the VOC isoprene in 62 study subjects during anesthesia and 16 spontaneously breathing healthy volunteers to determine (a) the influence of artificial and spontaneous ventilation and (b) the influence of study subject characteristics on breath isoprene concentrations. We used ion molecule reaction mass spectrometry for high-resolution breath-by-breath analysis of isoprene. We found that persons during anesthesia had significantly increased inspiratory and end-expiratory isoprene breath concentrations. Measured isoprene concentrations (median [first quartile-third quartile]) were in the anesthesia group: 54 [40-79] ppb (inspiratory) and 224 [171-309] ppb (end-expiratory), volunteer group: 14 [11-17] ppb (inspiratory) and 174 [124-202] ppb (end-expiratory). Higher end-tidal CO(2) concentrations in ventilated subjects were associated with higher expiratory isoprene levels. Furthermore, inspiratory and end-expiratory isoprene concentrations were correlated during anesthesia (r = 0.603, p < 0.001). Multivariate analysis showed that men had significantly higher end-expiratory isoprene concentrations than women. Rebreathing of isoprene from the anesthesia machine possibly accounts for the observed increase in isoprene in the anesthesia group.

  1. Stopped hearts, amputated toes and NASA: contemporary legends among healthy volunteers in US phase I clinical trials.

    PubMed

    Fisher, Jill A

    2015-01-01

    The first stage of testing new pharmaceuticals in humans is referred to as a phase I clinical trial. The purpose of these studies is to test the safety of the drugs and to establish appropriate doses that can later be given to patients. Most of these studies are conducted under controlled, in-patient conditions using healthy volunteers who are paid for their participation. To explore healthy volunteers' experiences in clinical trials, an ethnographic study was conducted at six in-patient phase I clinics in the USA. In addition to the observation of clinic activities (from informed consent procedures to dosing to blood draws), 268 semi-structured interviews were conducted, 33 with clinic staff and 235 with healthy volunteers. Drawing on this dataset, this article explores healthy volunteers' exchange of contemporary legends about phase I clinical trials. In addition to potentially scaring the listener and communicating distrust in the medical community, these incredible stories help participants cope with perceived stigma and establish a gradient of risk of trial participation, creating potential boundaries to their participation in medical research. The article argues that contemporary legends play a productive role in society, shaping how people view themselves and others and influencing their decisions about risky activities. PMID:25601069

  2. Intercentre reproducibility of cardiac apparent diffusion coefficient and fractional anisotropy in healthy volunteers

    PubMed Central

    2014-01-01

    Background Diffusion tensor cardiac magnetic resonance (DT-CMR) enables probing of the microarchitecture of the myocardium, but the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) reported in healthy volunteers have been inconsistent. The aim of this study was to validate a stimulated-echo diffusion sequence using phantoms, and to assess the intercentre reproducibility of in-vivo diffusion measures using the sequence. Methods and results A stimulated-echo, cardiac-gated DT-CMR sequence with a reduced-field-of-view, single-shot EPI readout was used at two centres with 3 T MRI scanners. Four alkane phantoms with known diffusivities were scanned at a single centre using a stimulated echo sequence and a spin-echo Stejskal-Tanner diffusion sequence. The median (maximum, minimum) difference between the DT-CMR sequence and Stejskal-Tanner sequence was 0.01 (0.04, 0.0006) × 10-3 mm2/s (2%), and between the DT-CMR sequence and literature diffusivities was 0.02 (0.05, 0.006) × 10-3 mm2/s (4%). The same ten healthy volunteers were scanned using the DT-CMR sequence at the two centres less than seven days apart. Average ADC and FA were calculated in a single mid-ventricular, short axis slice. Intercentre differences were tested for statistical significance at the p < 0.05 level using paired t-tests. The mean ADC ± standard deviation for all subjects averaged over both centres was 1.10 ± 0.06 × 10-3 mm2/s in systole and 1.20 ± 0.09 × 10-3 mm2/s in diastole; FA was 0.41 ± 0.04 in systole and 0.54 ± 0.03 in diastole. With similarly-drawn regions-of-interest, systolic ADC (difference 0.05 × 10-3 mm2/s), systolic FA (difference 0.003) and diastolic FA (difference 0.01) were not statistically significantly different between centres (p > 0.05), and only the diastolic ADC showed a statistically significant, but numerically small, difference of 0.07 × 10-3 mm2/s (p = 0.047). The intercentre, intrasubject coefficients

  3. Who is healthy? Aspects to consider when including healthy volunteers in QST--based studies-a consensus statement by the EUROPAIN and NEUROPAIN consortia.

    PubMed

    Gierthmühlen, Janne; Enax-Krumova, Elena K; Attal, Nadine; Bouhassira, Didier; Cruccu, Giorgio; Finnerup, Nanna B; Haanpää, Maija; Hansson, Per; Jensen, Troels S; Freynhagen, Rainer; Kennedy, Jeffrey D; Mainka, Tina; Rice, Andrew S C; Segerdahl, Märta; Sindrup, Søren H; Serra, Jordi; Tölle, Thomas; Treede, Rolf-Detlef; Baron, Ralf; Maier, Christoph

    2015-11-01

    Clinical and human experimental pain studies often include so-called "healthy" controls in investigations of sensory abnormalities, using quantitative sensory testing (QST) as an outcome measure. However, the criteria for what is considered "healthy" vary among the different studies and between study centers and investigators, partly explaining the high variability of the results. Therefore, several aspects should be considered during inclusion of healthy volunteers in QST-based trials to have homogenous groups of healthy controls with less variability between human experimental studies, so that results are less likely to be false negative or false positive because of subject-related factors. The EUROPAIN and NEUROPAIN consortia aimed to define factors influencing the variability in selection of healthy subjects in QST-based studies before the start of both projects and to give recommendations how to minimize it based on the current literature and expertise of the participants. The present suggestions for inclusion criteria of healthy volunteers into QST-based trials describe a 2-level approach including standardized questionnaires enabling the collection of relevant information on sociodemographic data, medical history, current health status, coping strategies in dealing with pain, and the motivation of the volunteer to participate in the study. These suggestions are believed to help researchers interpret their results in comparison with others and improve the quality of clinical studies including healthy volunteers as controls or in human experimental pain studies. They aim to reduce any confounding factors. Furthermore, the acquired information will allow post hoc analyses of variance for different potential influencing factors.

  4. Assessment of Tandem Measurements of pH and Total Gut Transit Time in Healthy Volunteers

    PubMed Central

    Mikolajczyk, Adam E; Watson, Sydeaka; Surma, Bonnie L; Rubin, David T

    2015-01-01

    Objectives: The variation of luminal pH and transit time in an individual is unknown, yet is necessary to interpret single measurements. This study aimed to assess the intrasubject variability of gut pH and transit time in healthy volunteers using SmartPill devices (Covidien, Minneapolis, MN). Methods: Each subject (n=10) ingested two SmartPill devices separated by 24 h. Mean pH values were calculated for 30 min after gastric emptying (AGE), before the ileocecal (BIC) valve, after the ileocecal (AIC) valve, and before body exit (BBE). Intrasubject variability was determined by comparing mean values from both ingestions for an individual subject using standard deviations, 95% limits of agreement, and Bland-Altman plots. Results: Tandem device ingestion occurred without complication. The median (full range) intrasubject standard deviations for pH were 0.02 (0.0002–0.2048) for AGE, 0.06 (0.0002–0.3445) for BIC, 0.14 (0.0018–0.3042) for AIC, and 0.08 (0.0098–0.5202) for BBE. There was a significant change in pH for AIC (mean difference: −0.45±0.31, P=0.0015) observed across all subjects. The mean coefficients of variation for transit time were 12.0±7.4% and 25.8±15.8% for small and large bowels, respectively (P=0.01). Conclusions: This study demonstrates the safety and feasibility of tandem gut transit and pH assessments using the SmartPill device. In healthy individuals and over 24 h, the gut pH profile does not markedly fluctuate in a given region with more variation seen in the colon compared with the small bowel, which has important implications for future physiology and drug delivery studies. PMID:26158610

  5. Effects of Metoclopramide on Esophageal Motor Activity and Esophagogastric Junction Compliance in Healthy Volunteers

    PubMed Central

    Mikami, Hironobu; Ishimura, Norihisa; Fukazawa, Kousuke; Okada, Mayumi; Izumi, Daisuke; Shimura, Shino; Okimoto, Eiko; Aimi, Masahito; Ishihara, Shunji; Kinoshita, Yoshikazu

    2016-01-01

    Background/Aims Prokinetic drugs such as metoclopramide are frequently used as second-line therapy for patients with gastroesophageal reflux disease. However, their beneficial effects remain unclear. Esophageal motor activities and compliance of the esophagogastric junction (EGJ) are important for prevention of gastroesophageal reflux. Although metoclopramide has been reported to increase lower esophageal sphincter (LES) pressure, its effects on EGJ compliance have not been evaluated. In the present study, we investigated the effects of metoclopramide on esophageal motor activities and EGJ compliance. Methods Nine healthy male volunteers without abdominal symptoms were enrolled. Peristaltic esophageal contractions and LES pressure were examined using high-resolution esophageal manometry, while EGJ compliance was evaluated with an endoluminal functional lumen-imaging probe. After obtaining baseline values for esophageal motor activities and EGJ compliance, metoclopramide (10 mg) was intravenously administered, then all measurements were repeated at 15 minutes after administration in each subject. Results Following administration of metoclopramide, mean resting LES pressure was significantly increased as compared with the baseline (13.7 ± 9.2 vs 26.7 ± 8.8 mmHg, P < 0.05). In addition, metoclopramide significantly augmented peristaltic contractions, especially in the distal esophageal segment (P < 0.05). On the other hand, distensibility index did not change after administration (4.5 ± 0.5 vs 4.1 ± 0.5 mm2/mmHg), suggesting no significant effect of metoclopramide on EGJ compliance. Conclusions Metoclopramide augmented esophageal contractions without changing EGJ compliance in healthy adults. PMID:26507875

  6. Pharmacokinetics of posaconazole administered orally or by nasogastric tube in healthy volunteers.

    PubMed

    Dodds Ashley, Elizabeth S; Varkey, Jay B; Krishna, Gopal; Vickery, Donna; Ma, Lei; Yu, Xin; Malavade, Darshana; Goodwin, Megan; Perfect, John R; Power, Eddie

    2009-07-01

    The use of a nasogastric tube is one means of administering antifungal therapy to critically ill patients unable to receive medication via the oral route. This was a phase 1, open-label, single-center, randomized, crossover study of posaconazole administered via nasogastric tube in healthy volunteers. Each subject received two 400-mg single doses of posaconazole, one administered orally and one administered by nasogastric tube, with a 7-day washout period between each dose. Posaconazole was administered 5 to 10 min after subjects received a nutritional supplement. Blood samples for pharmacokinetic analysis were obtained up to 120 h postdose. The analysis of variance estimate of the study population suggests that the posaconazole nasogastric tube administration least-square mean values of observed maximum concentration (C(max)), area under the plasma concentration-time curve (AUC) to the last measurable concentration, and AUC to time infinity were 81%, 76%, and 77%, respectively, of the corresponding oral administration values. The reason for lower C(max) and AUC values when posaconazole is administered via the nasogastric tube route is not known. Oral and nasogastric tube administration of a single 400-mg dose of posaconazole suspension was safe and well tolerated in healthy adult subjects. The incidence and nature of treatment-emergent adverse events were similar with both administration routes, and no serious adverse events or clinically significant laboratory test or vital sign abnormalities were reported. Obtaining plasma posaconazole concentrations may be warranted when posaconazole is given to patients via a nasogastric tube to ensure adequate posaconazole exposure. Strategies that have been shown to enhance posaconazole exposure (such as splitting the dose and minimizing the use of proton pump inhibitors) may also be used.

  7. Effect of Single-dose Rifampin on the Pharmacokinetics of Warfarin in Healthy Volunteers

    PubMed Central

    Frymoyer, A; Shugarts, S; Browne, M; Wu, AHB; Frassetto, L; Benet, LZ

    2011-01-01

    Based on in vitro rat and human hepatocyte uptake studies showing inhibition of warfarin uptake in the presence of the non-specific organic anion transporting polypeptide (OATP) inhibitor rifampin, a clinical study was conducted in 10 healthy volunteers. In a randomized, single-dose, two-period, crossover design, subjects received a 7.5 mg dose of warfarin alone or immediately following a 600 mg intravenous dose of rifampin. Rifampin did not significantly alter R- or S- warfarin area under the concentration-time curve (AUC) from 0–12 hours (period of hepatic OATP inhibition by rifampin) or Cmax (maximum plasma concentration). AUC0–∞ was decreased on rifampin days for both R- (25% reduction; p < 0.001) and S-warfarin (15% reduction; p < 0.05). No differences were seen on the area under the INR-time curve. Our study suggests hepatic uptake via OATPs may not be clinically important in the pharmacokinetics of warfarin. PMID:20703222

  8. Bioequivalence of two brands of ciprofloxacin 750 mg tablets (Sarf and Ciprobay) in healthy human volunteers.

    PubMed

    Abdallah, R M; Alam, S M; Awaad, F M; Dham, R; El-Kersh, A; El-Laithy, A; Shalby, M H; Shihabeddin, M; El-Walily, A F; Yacout, M; Zaman, Q

    2002-04-01

    An open, randomized, two-way crossover study was carried out in 28 healthy volunteers at Gulf Pharmaceutical Industries (Julphar), as a joint venture with Saqr Hospital, Ras Al-Khaimah, UAE. The two commercial brands used were Sarf (Julphar, UAE) as test and Ciprobay (Bayer AG, Germany) as reference product. The drug was administered to each subject with 240 mL of water after an overnight fasting in two treatment days separated by a one-week washout period. After dosing, serial blood samples were collected for a period of 24 hr and serum was separated and analyzed for ciprofloxacin using a sensitive, reproducible, and accurate high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection. Various pharmacokinetic parameters, including AUC0-t, AUC0-infinity, Cmax, Tmax, t1/2, and lambdaz, were determined from ciprofloxacin serum concentration-time profiles for both formulations and found to be in good agreement with reported values. The parameters AUC0-t, AUC0-infinity, and Cmax were tested for bioequivalence after log-transformation of data. No significant difference was found based on analysis of variance (ANOVA); the 90% confidence intervals (95.73-107.62%, 94.98-108.26%, 92.80-103.90% for AUC0-t, AUC0-infinity, Cmax, respectively) for the test/reference ratios of these parameters were within the bioequivalence acceptance range of 80-125%. Based on this data, it is concluded that both formulations are bioequivalent and are interchangeable in medical practice.

  9. Dietary intake of melatonin from tropical fruit altered urinary excretion of 6-sulfatoxymelatonin in healthy volunteers.

    PubMed

    Johns, Nutjaree Pratheepawanit; Johns, Jeffrey; Porasuphatana, Supatra; Plaimee, Preeyaporn; Sae-Teaw, Manit

    2013-01-30

    This study assessed the melatonin content of six tropical fruits and examined whether human consumption could contribute to dietary melatonin as measured by 6-sulfatoxymelatonin (aMT6-s, a marker of circulating melatonin in the body). Melatonin was extracted using methanol and analyzed by high-performance liquid chromatography. In a clinical crossover study, 30 healthy volunteers consumed selected fruits one at a time, with a 1week wash-out period between fruits, until completing all six fruits. Most fruits had moderate melatonin content. Significant increases in urine aMT6-s concentrations were seen after the consumption of pineapple (266%, p = 0.004), banana (180%, p = 0.001), and orange (47%, p = 0.007). The need to analyze melatonin both in fruit and as in vivo uptake was demonstrated. Further study is warranted regarding the clinical effect of fruit consumption in people with age-related melatonin reduction problems such as sleeplessness and illnesses involving oxidative damage.

  10. A pharmacoscintigraphic study of three time-delayed capsule formulations in healthy male volunteers.

    PubMed

    McConville, Jason T; Hodges, Lee-Ann; Jones, Tamara; Band, Janet P; O'Mahony, Bridget; Lindsay, Blythe; Ross, Alistair C; Florence, Alastair J; Stanley, Adrian J; Humphrey, Michael J; Wilson, Clive G; Stevens, Howard N E

    2009-11-01

    Three time-delayed capsule (TDC) formulations were investigated in a pharmacoscintigraphic study, using a three-way crossover design in eight healthy male volunteers. Additionally, the pulsed release of a TDC was investigated with time-lapse photography, using a nondisintegrating riboflavin tablet. The photographic study indicated how the release characteristics of the TDC relied on the erosion of a tablet containing hypromellose (HPMC). Each TDC was duel radio labelled with indium-111 and technetium-99 m DTPA complexes, to observe drug release scintigraphically (theophylline was a marker compound). Three formulations, having in vitro dissolution release times of 1.8, 2.9 or 4.0 h were shown to compare favourably with mean in vivo scintigraphic release times of 2.7, 3.0 and 4.0 h for each formulation containing 20, 24 or 35% (w/w) HPMC concentrations respectively. An increase in HPMC concentration was associated with a delayed technetium release time, and followed the same rank order as the in vitro dissolution study. Observed radiolabel dispersion always occurred in the small intestine. In conclusion, the study established that the TDC performs and demonstrates an in vitro-in vivo correlation. Additionally, time and site of release were accurately visualized by gamma scintigraphy, and confirmed with determination of theophylline absorption. PMID:19387976

  11. Brain-Modulated Effects of Auricular Acupressure on the Regulation of Autonomic Function in Healthy Volunteers

    PubMed Central

    Gao, Xin-Yan; Wang, Lu; Gaischek, Ingrid; Michenthaler, Yvonne; Zhu, Bing; Litscher, Gerhard

    2012-01-01

    Auricular acupuncture has been described in ancient China as well as Egypt, Greece, and Rome. At the end of the 1950s, ear acupuncture was further developed by the French physician Dr. Paul Nogier. The goal of this study was to develop a new system for ear acupressure (vibration stimulation) and to perform pilot investigations on the possible acute effects of vibration and manual ear acupressure on heart rate (HR), heart rate variability (HRV), pulse wave velocity (PWV), and the augmentation index (AIx) using new noninvasive recording methods. Investigations were performed in 14 healthy volunteers (mean age ± SD: 26.3 ± 4.3 years; 9 females, 5 males) before, during, and after acupressure vibration and manual acupressure stimulation at the “heart” auricular acupuncture point. The results showed a significant decrease in HR (P ≤ 0.001) and a significant increase in HRV total (P = 0.008) after manual ear acupressure. The PWV decreased markedly (yet insignificantly) whereas the AIx increased immediately after both methods of stimulation. The increase in the low-frequency band of HRV was mainly based on the intensification of the related mechanism of blood pressure regulation (10-s-rhythm). Further studies in Beijing using animal models and investigations in Graz using human subjects are already in progress. PMID:21904563

  12. Effects of Different Therapeutic Ultrasound Waveforms on Endothelial Function in Healthy Volunteers: A Randomized Clinical Trial.

    PubMed

    Cruz, Jeferson Mendes; Hauck, Melina; Cardoso Pereira, Ana Paula; Moraes, Maicon Borges; Martins, Cassio Noronha; da Silva Paulitsch, Felipe; Plentz, Rodrigo Della Méa; Peres, William; Vargas da Silva, Antônio Marcos; Signori, Luis Ulisses

    2016-02-01

    The purpose of this study was to determine the effects of different therapeutic 1-MHz ultrasound waveforms on endothelial function before and after cyclooxygenase (COX) inhibition. Forty-two healthy volunteers aged 27.2 ± 3.8 y underwent interventions and an evaluation for endothelial function (n = 15; with COX inhibition, n = 15; duration of the vasodilator effect, n = 12) by technique flow-mediated dilation. Continuous ultrasound therapy (0.4 W/cm(2 SATA)), pulsed ultrasound therapy (20% duty cycle, 0.08 W/cm(2 SATA)) or placebo (equipment power off) was randomly applied over the brachial artery for 5 min. COX inhibition (aspirin) was carried out 30 min before treatments. In relation to the placebo, flow-mediated dilation increased by 4.8% using continuous ultrasound and by 3.4% using pulsed ultrasound. After COX, flow-mediated dilation was enhanced by 2.1% by continuous ultrasound and 2.6% by pulsed ultrasound. This vasodilation persisted for 20 min. Continuous and pulsed therapeutic 1-MHz ultrasound waveforms improved endothelial function in humans, which provided them with anti-inflammatory vascular effects.

  13. Bioavailability of an R-α-Lipoic Acid/γ-Cyclodextrin Complex in Healthy Volunteers

    PubMed Central

    Ikuta, Naoko; Okamoto, Hinako; Furune, Takahiro; Uekaji, Yukiko; Terao, Keiji; Uchida, Ryota; Iwamoto, Kosuke; Miyajima, Atsushi; Hirota, Takashi; Sakamoto, Norihiro

    2016-01-01

    R-α-lipoic acid (R-LA) is a cofactor of mitochondrial enzymes and a very strong antioxidant. R-LA is available as a functional food ingredient but is unstable against heat or acid. Stabilized R-LA was prepared through complexation with γ-cyclodextrin (CD), yielding R-LA/CD. R-LA/CD was orally administered to six healthy volunteers and showed higher plasma levels with an area under the plasma concentration-time curve that was 2.5 times higher than that after oral administration of non-complexed R-LA, although the time to reach the maximum plasma concentration and half-life did not differ. Furthermore, the plasma glucose level after a single oral administration of R-LA/CD or R-LA was not affected and no side effects were observed. These results indicate that R-LA/CD could be easily absorbed in the intestine. In conclusion, γ-CD complexation is a promising technology for delivering functional but unstable ingredients like R-LA. PMID:27314343

  14. Intrapulmonary pharmacokinetics of azithromycin in healthy volunteers given five oral doses.

    PubMed Central

    Olsen, K M; San Pedro, G; Gann, L P; Gubbins, P O; Halinski, D M; Campbell, G D

    1996-01-01

    The intrapulmonary pharmacokinetics of oral azithromycin were studied in 25 healthy volunteers, each of whom received an initial dose of 500 mg and then 250 mg once daily for four additional doses. Bronchoscopy, bronchoalveolar lavage, and venipuncture were performed 4, 28, 76, 124, 172, 244, 340, and 508 h after the first dose was administered. Azithromycin concentrations in epithelial lining fluid (ELF), alveolar macrophages, peripheral blood monocytes, and serum were measured by high-performance liquid chromatography. Azithromycin was extensively concentrated in cells and ELF. Drug concentrations in AMs (peak mean +/- standard deviation, 464 +/- 65 micrograms/ml) exceeded 80 micrograms/ml up to 508 h (21 days) following the first dose, while concentrations in PBMs (peak, 124 +/- 28 micrograms/ml) exceeded 20 micrograms/ml up to 340 h (14 days). Azithromycin concentrations in ELF peaked at 124 h (3.12 +/- 0.93 micrograms/ml) and were detectable up to 172 h (7 days), when they were 20 times the concurrent serum concentrations. Although the clinical significance of antibiotic concentrations in these compartments is nuclear, the sustained lung tissue penetration and extensive phagocytic accumulation demonstrated in this study support the proven efficacy of azithromycin administered on a 5-day dosage schedule in the treatment of extracellular or intracellular pulmonary infections. PMID:8913469

  15. Diuretic effect of powdered Cerasus avium (cherry) tails on healthy volunteers.

    PubMed

    Hooman, Nakysa; Mojab, Faraz; Nickavar, Bahman; Pouryousefi-Kermani, Pouran

    2009-10-01

    In this study, the diuretic activity of powdered cherry stalk was evaluated in 13 healthy volunteers by means of their water balance. In addition to biochemical parameters, such as urinary electrolyte concentration, osmolality and any adverse reaction were determined. The capsules of cherry stalks were administered at an equivalent dose of 2.0 grams of the plant per person. Urinary biochemical determination was made of concentration of electrolytes (sodium, potassium, chloride and calcium), urinary volume and osmolality by standard laboratory procedures. Statistical evaluation was performed by Student's-t and Wilcoxon rank tests. After administration of cherry stalk, the mean of urine calcium, sodium, chloride, and urine volume increased, but the amount of urine potassium and urine osmolality did not change. No adverse reaction was observed. Powdered C. avium stalk increased mild urine volume confirming thus the claimed diuretic effect of the herb. Administration of cherry stalk caused urinary sodium and chloride rising less than loop diuretics but higher than the others. Because of rising calcium excretion, it should be used with cautious in those with urolithiasis. PMID:19783515

  16. Functional biomarkers for the acute effects of alcohol on the central nervous system in healthy volunteers

    PubMed Central

    Zoethout, Remco W M; Delgado, Wilson L; Ippel, Annelies E; Dahan, Albert; van Gerven, Joop M A

    2011-01-01

    The central nervous system (CNS) effects of acute alcohol administration have been frequently assessed. Such studies often use a wide range of methods to study each of these effects. Unfortunately, the sensitivity of these tests has not completely been ascertained. A literature search was performed to recognize the most useful tests (or biomarkers) for identifying the acute CNS effects of alcohol in healthy volunteers. All tests were grouped in clusters and functional domains. Afterwards, the effect of alcohol administration on these tests was scored as improvement, impairment or as no effect. Furthermore, dose–response relationships were established. A total number of 218 studies, describing 342 different tests (or test variants) were evaluated. Alcohol affected a wide range of CNS domains. Divided attention, focused attention, visuo-motor control and scales of feeling high and of subjective drug effects were identified as the most sensitive functional biomarkers for the acute CNS effects of alcohol. The large number of CNS tests that are used to determine the effects of alcohol interferes with the identification of the most sensitive ones and of drug–response relationships. Our results may be helpful in selecting rational biomarkers for studies investigating the acute CNS effects of alcohol or for future alcohol- interaction studies. PMID:21284693

  17. Scintigraphic evaluation of colon targeting pectin-HPMC tablets in healthy volunteers.

    PubMed

    Hodges, L A; Connolly, S M; Band, J; O'Mahony, B; Ugurlu, T; Turkoglu, M; Wilson, C G; Stevens, H N E

    2009-03-31

    The in vivo evaluation of colon-targeting tablets was conducted in six healthy male volunteers. A pectin-hydroxypropyl methylcellulose coating was compressed onto core tablets labelled with 4MBq (99m)Tc-DTPA. The tablets released in the colon in all subjects; three in the ascending colon (AC) and three in the transverse colon (TC). Tablets that released in the TC had reached the AC before or just after food (Group A). The other three tablets released immediately upon AC entry at least 1.5h post-meal (Group B). Release onset for Group B was earlier than Group A (343min vs 448min). Group B tablets exhibited a clear residence period at the ileocaecal junction (ICJ) which was not observed in Group A. Prolonged residence at the ICJ is assumed to have increased hydration of the hydrogel layer surrounding the core tablet. Forces applied as the tablets progressed through the ICJ may have disrupted the hydrogel layer sufficiently to initiate radiolabel release. Conversely, Group A tablets moved rapidly through the AC to the TC, possibly minimising contact times with water pockets. Inadequate prior hydration of the hydrogel layer preventing access of pectinolytic enzymes and reduced fluid availability in the TC may have retarded tablet disintegration and radiolabel diffusion.

  18. Bioequivalence Study of Two Orodispersible Rizatriptan Formulations of 10 mg in Healthy Volunteers

    PubMed Central

    Cánovas, Mercè; Polonio, Francisco; Cabré, Francesc

    2016-01-01

    The aim of the study was to assess the bioequivalence and tolerability of two different oral formulations of rizatriptan. A bioequivalence study was carried out in 40 healthy volunteers according to an open label, randomized, two-period, two-sequence, crossover, single dose, and fasting conditions design. The test and reference formulations were administered in two treatment days, separated by a washout period of seven days. Plasma concentrations of rizatriptan were obtained by the LC/MS/MS (Liquid chromatography tandem-mass spectrometry) method. Log-transformed AUC0-t (area under the plasma concentration-time curve from zero to the last measurable concentration) and Cmax (maximum plasma concentration) values were tested for bioequivalence based on the ratios of the geometric means (test/reference). The tmax (time to reach maximum plasma concentration) was analysed nonparametrically. The 90% confidence intervals of the geometric mean values for the test/reference ratios for AUC0-t and Cmax were within the bioequivalence acceptance range of 80%–125%. According to the European Guideline, it may therefore be concluded that the test formulation of rizatriptan 10 mg orodispersible tablet is bioequivalent to the reference formulation (Maxalt® Max 10 mg oral lyophilisate). The safety profile of both formulations was consistent with the summary of the product characteristics.

  19. Accuracy of the Lifebox pulse oximeter during hypoxia in healthy volunteers.

    PubMed

    Dubowitz, G; Breyer, K; Lipnick, M; Sall, J W; Feiner, J; Ikeda, K; MacLeod, D B; Bickler, P E

    2013-12-01

    Pulse oximetry is a standard of care during anaesthesia in high-income countries. However, 70% of operating environments in low- and middle-income countries have no pulse oximeter. The 'Lifebox' oximetry project set out to bridge this gap with an inexpensive oximeter meeting CE (European Conformity) and ISO (International Organization for Standardization) standards. To date, there are no performance-specific accuracy data on this instrument. The aim of this study was to establish whether the Lifebox pulse oximeter provides clinically reliable haemoglobin oxygen saturation (Sp O2 ) readings meeting USA Food and Drug Administration 510(k) standards. Using healthy volunteers, inspired oxygen fraction was adjusted to produce arterial haemoglobin oxygen saturation (Sa O2 ) readings between 71% and 100% measured with a multi-wavelength oximeter. Lifebox accuracy was expressed using bias (Sp O2 - Sa O2 ), precision (SD of the bias) and the root mean square error (Arms). Simultaneous readings of Sa O2 and Sp O2 in 57 subjects showed a mean (SD) bias of -0.41% (2.28%) and Arms 2.31%. The Lifebox pulse oximeter meets current USA Food and Drug Administration standards for accuracy, thus representing an inexpensive solution for patient monitoring without compromising standards.

  20. Pulmonary distribution and clearance of two beclomethasone liposome formulations in healthy volunteers.

    PubMed

    Saari, M; Vidgren, M T; Koskinen, M O; Turjanmaa, V M; Nieminen, M M

    1999-04-20

    The pulmonary distribution and clearance of 99mTc-labelled beclomethasone dipropionate (Bec) dilauroylphosphatidylcholine (DLPC) and dipalmitoylphosphatidylcholine (DPPC) liposomes were compared in 11 healthy volunteers using gamma scintigraphy. As delivered by using the Aerotech jet nebulizer both liposome aerosols had a suitable droplet size (mass median aerodynamic diameter 1.3 microm) allowing deep pulmonary deposition. However, in the total drug output during the inhalation there was a relatively large difference between DLPC and DPPC of 11.4 and 3.1 microg, respectively. In a gamma camera study no significant differences existed in the central/peripheral lung deposition between the DLPC and DPPC formulations. Progressive clearance of both Tc-labelled Bec liposomes was seen: 24 h after inhalation, 79% of the originally deposited radioactivity of DLPC liposomes and 83% of that of DPPC liposomes remained in the lungs. Thus there was slightly slower clearance of inhaled liposomes using DPPC instead of DLPC. We conclude that both liposome formulations are suitable for nebulization, although aerosol clouds were more efficiently made from the DLPC liposome suspension. Our results support the view that liposome encapsulation of a drug can offer sustained release and drug action in the lower airways.

  1. The pharmacokinetics of subcutaneously injected Bimosiamose disodium in healthy male volunteers.

    PubMed

    Meyer, Michael; Beyer, Diana; Vollhardt, Karin; Woischwill, Christiane; Jilma, Bernd; Wolff, Gerhard

    2007-12-01

    Bimosiamose is a novel synthetic pan-selectin antagonist developed for the treatment of acute and chronic inflammatory disorders. Therefore the pharmacokinetics of Bimosiamose disodium were studied in healthy male volunteers after single and multiple subcutaneous injections. A randomized, double-blind, placebo-controlled dose escalation trial was carried out. The subjects received subcutaneous injections of placebo or 100, 200 or 300 mg Bimosiamose disodium into the abdomen. Plasma and urine concentrations of Bimosiamose were determined. The maximum plasma concentration was 2.17+/-0.70 microg/ml and the AUC(0-infinity) 11.1+/-2.9 h microg/ml after the highest dose on day 1 (mean+/-SD). For the apparent clearance CL/f 28.7+/-7.3 l/h and the terminal half life t(1/2) 3.7+/-0.6 h were calculated. The mean residence time MRT(infinity) of 5.5 to 6.3 h for s.c. injection exceeded that after i.v. infusion due to an extended absorption time. For multiple dosing, constant pre-dose concentrations of about 20 ng/ml may be reached after two subsequent doses of 200 or 300 mg Bimosiamose disodium once daily. Almost 15% of the administered drug was excreted unchanged in urine. Moreover, Bimosiamose was well tolerated. PMID:17876866

  2. Effect of ethanol on dynamic visual acuity during vertical body oscillation in healthy volunteers.

    PubMed

    Schmäl, F; Kunz, R; Ortmann, C; Stoll, W; Nieschalk, M; Fechner, G

    2000-11-01

    Visual orientation is the most important sensory input during locomotion (e.g. walking, driving a car, riding a bicycle). We investigated dynamic visual acuity (DVA) during vertical body-oscillations (amplitude 5 cm; frequency 1.5 Hz) in 12 healthy subjects before and twice after ethanol consumption. During oscillation, vertical eye movements were recorded under two test conditions: with eyes closed (EC) and during DVA testing. A significant increase in vertical eye-amplitude after ethanol ingestion occurred only during EC tests, as a possible sign of vestibular hyperreaction. During vestibular stimulation alone (EC), ethanol did not affect the phase shift between stimulus and eye movements. However, when the subjects were given an additional visual stimulus (DVA), the post-alcohol phase shift rose significantly. Surprisingly, the post-alcohol phase shift values for the two test conditions showed no significant differences. After ethanol ingestion we found no changes in static visual acuity but a significant loss of DVA. Volunteers with a change of DVA threshold (DVAT) showed significantly (P = 0.004) higher post-alcoholic changes in the phase shift. In summary, low doses of ethanol disturbed the visually guided oculomotor response during fixation of an earth-fixed target while the observer was subject to linear vertical acceleration. This effect led to an increasing delay between the beginning of body and eye movements. The consequence was an increasing phase shift and thus a decrease in DVA during whole-body oscillation which was comparable to movements during human locomotion.

  3. Effect of dehusked Garcinia kola seed on the overall pharmacokinetics of quinine in healthy Nigerian volunteers

    PubMed Central

    Igbinoba, Sharon I.; Onyeji, Cyprian O.; Akanmu, Moses A.; Soyinka, Julius O.; Pullela, Srirama Sarma V.V; Cook, James M.; Nathaniel, Thomas I.

    2016-01-01

    We investigated the effect of concurrent ingestion of Garcinia kola seed on the pharmacokinetics of quinine. In a randomized crossover study, 24 healthy Nigerian volunteers were assigned into two groups (A and B; n = 12 per group) on the basis of G. kola dose orally ingested. Each subject received 600mg quinine sulphate before and after ingesting 12.5g of G. kola once daily for seven days (Group A) or 12.5g twice daily for six days and once on the seventh day (Group B). Blood samples were collected and analyzed for plasma quinine and its metabolite, (3-hydroxyquinine) using a validated HPLC method. Concurrent administration of quinine with G. kola reduced quinine tmax by 48% (group A), mean Cmax by 19% and 26% in groups A and B, and slight reduction in mean AUC0–∞ of quinine in both groups. 3-hydroxyquinine Cmax also reduced by 29% and 32%; AUC0–∞ by 13% and 9% respectively. The point estimates of the T/R ratio of the geometric means for all Cmax obtained and only the AUC0–∞ at a higher dose of G. kola were outside the 80–125% bioequivalence range. In conclusion, an herb-drug interaction was noted with concurrent quinine and G. kola administration. PMID:25328082

  4. The Northwick Park tragedy--protecting healthy volunteers in future first-in-man trials.

    PubMed

    Dowsing, T; Kendall, M J

    2007-06-01

    The development of potentially powerful drugs which may become effective in the treatment for disorders currently difficult to manage presents the pharmaceutical industry and the scientific community with a major challenge. Such drugs with novel modes of action and the capacity to modify the body's immune system could also be very toxic. The possibility became a tragic reality on March 13th 2006 when TGN1412 was given to six healthy volunteers at Northwick Park hospital. All six became seriously ill. Fortunately none died but some were left with serious residual defects. The British Secretary of State for Health set up an Expert Scientific Group to investigate this tragic event. The report had to make recommendations designed to prevent a recurrence whilst not unduly delaying or discouraging the development of new drugs designed to treat cancers and other serious disorders. They made 22 recommendations. The drug TGN1412 had been shown to be well tolerated by non-human primates. A recent report on non-human primates in research recommended their continued use in some forms of research, for example on brain disorders. However, they also recommended that non-human primates should be used sparingly and only when justified scientifically. Their treatment should be optimal and research on them should be restricted to selected centres of expertise. The tragedy at Northwick Park should encourage the Pharmaceutical Industry to rethink their use of non-human primates in drug toxicity testing and hopefully to reduce their use and treat them better.

  5. Alprazolam 0.125 mg twice a day improves aspects of psychometric performance in healthy volunteers.

    PubMed

    Bourin, M; Colombel, M C; Guitton, B

    1998-10-01

    The effects of alprazolam (0.125 mg) taken twice a day on several cognitive and performance tasks (Pictures test, Digit-Symbol Substitution Test, Choice Reaction Time [CRT], Critical Flicker Fusion [CFF]) were investigated in healthy students. A double-blind, independent group design was used to compare placebo with alprazolam (32 volunteers in each group). After random assignment, all subjects received placebo for 3 days (D) followed by 14 days of treatment with either alprazolam or placebo. Subjects completed a battery of tests at D0, D3, D7, D10, and D14. D3 performance was poorer in the alprazolam group except for CFF values (ascending values and total values), and the only significant improvement was in total reaction time on the CRT test. However, a significant improvement in performance (except in recognition reaction time) was shown at D7, D10, and D14 in the alprazolam group compared with the control group results. This study shows that repeated low doses of alprazolam produce small improvements in some aspects of psychomotor and cognitive functions. Training effect, tolerance effect, anxiolytic effect, and changes in receptor function and/or number are discussed to explain the performance improvement.

  6. Comparative pharmacokinetic and pharmacodynamic evaluation of branded and generic formulations of meloxicam in healthy male volunteers

    PubMed Central

    Tacca, Mario Del; Pasqualetti, Giuseppe; Gori, Giovanni; Pepe, Pasquale; Di Paolo, Antonello; Lastella, Marianna; De Negri, Ferdinando; Blandizzi, Corrado

    2013-01-01

    Purpose The primary aim of the present study was to assess the pharmacokinetic bioequivalence between a generic formulation of meloxicam 15 mg tablets (Meloxicam Hexal) and its respective brand product (Mobic), in order to verify whether the generic product conforms to the regulatory standards of bioequivalence in the postmarketing setting. As a secondary exploratory aim, the pharmacodynamic effects of the two formulations were also evaluated by means of rating scales following hyperalgesia induced by cutaneous freeze injury. Subjects and methods A single 15 mg dose of generic or branded meloxicam tablets was administered to 24 healthy male volunteers in a crossover fashion. Plasma samples, collected for 24 hours after dosing, were assayed for meloxicam concentration by a validated highperformance liquid chromatography method. Results The analysis of pharmacokinetic parameters did not show any significant difference between the two meloxicam formulations: the 90% confidence intervals fell within the acceptance range of 80%–125% (0.84–1.16 for area under the curve [0–24], and 0.89–1.23 for peak concentration). No difference in the pharmacodynamic end point was observed between the two groups. Conclusion The pharmacokinetic profiles of the two meloxicam formulations confirm the regulatory criteria for bioequivalence; pharmacodynamic data indicate a similar antihyperalgesic effect. The two formulations can be used interchangeably in the clinical setting. PMID:23901278

  7. Acute neuropsychological effects of MDMA and ethanol (co-)administration in healthy volunteers

    PubMed Central

    Wezenberg, E.; Valkenberg, M. M. G. J.; de Jong, C. A. J.; Buitelaar, J. K.; van Gerven, J. M. A.; Verkes, R. J.

    2008-01-01

    Rationale In Western societies, a considerable percentage of young people expose themselves to 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”). Commonly, ecstasy is used in combination with other substances, in particular alcohol (ethanol). MDMA induces both arousing as well as hallucinogenic effects, whereas ethanol is a general central nervous system depressant. Objective The aim of the present study is to assess the acute effects of single and co-administration of MDMA and ethanol on executive, memory, psychomotor, visuomotor, visuospatial and attention function, as well as on subjective experience. Materials and methods We performed a four-way, double-blind, randomised, crossover, placebo-controlled study in 16 healthy volunteers (nine male, seven female) between the ages of 18–29. MDMA was given orally (100 mg) and blood alcohol concentration was maintained at 0.6‰ by an ethanol infusion regime. Results Co-administration of MDMA and ethanol was well tolerated and did not show greater impairment of performance compared to the single-drug conditions. Impaired memory function was consistently observed after all drug conditions, whereas impairment of psychomotor function and attention was less consistent across drug conditions. Conclusions Co-administration of MDMA and ethanol did not exacerbate the effects of either drug alone. Although the impairment of performance by all drug conditions was relatively moderate, all induced significant impairment of cognitive function. PMID:18305926

  8. Incidence of associated events during the performance of invasive procedures in healthy human volunteers

    NASA Technical Reports Server (NTRS)

    Highstead, R. Grant; Tipton, Kevin D.; Creson, Daniel L.; Wolfe, Robert R.; Ferrando, Arny A.

    2005-01-01

    Metabolic investigations often utilize arteriovenous sampling and muscle biopsy. These investigations represent some risk to the subject. We examined 369 studies performed in the General Clinical Research Center between January 1994 and May 2003 for events related to femoral catheterization and muscle biopsies. Incidents were further examined by age (younger: 18-59 yr, n=133; and older: 60-76 yr, n=28). There were no clinically defined major complications associated with either procedure. The incidence of femoral catheter repositioning or reinsertion was higher in the older group (25.5 vs. 9.7%). There was no difference in the incidence of premature removal of catheters, ecchymosis or hematoma, or the persistence of pain after discharge. The occurrence of all incidents did not increase with multiple catheterizations. Muscle biopsy was associated with infrequent ecchymosis or hematoma in both groups (1.1 and 3.6% in younger and older groups, respectively). Both procedures entail a small likelihood of a vagallike response (3.3% overall), resulting in nausea, dizziness, and rarely a loss of consciousness. These results indicate that, in skilled hands and a defined clinical setting, the incidents associated with femoral catheterization and muscle biopsy in healthy volunteers are reasonable and largely controllable.

  9. Concentrations of gemifloxacin at the target site in healthy volunteers after a single oral dose.

    PubMed

    Islinger, Florian; Bouw, Rene; Stahl, Mathias; Lackner, Edith; Zeleny, Petra; Brunner, Martin; Müller, Markus; Eichler, Hans Georg; Joukhadar, Christian

    2004-11-01

    Free gemifloxacin concentrations in the interstitial space fluid of skeletal muscle and subcutaneous adipose tissue were measured by means of in vivo microdialysis to characterize the ability of gemifloxacin to penetrate human soft tissues. Twelve healthy volunteers received a single oral dose of 320 mg of gemifloxacin. The mean areas under the concentration-time curves from 0 to 10 h (AUC(0-10)) were significantly higher for soft tissue than for unbound gemifloxacin in plasma (P < 0.05). The ratios of the mean AUC(0-10) for tissue to the AUC(0-10) for free gemifloxacin in plasma were 1.7 +/- 0.7 (mean +/- standard deviation) for skeletal muscle and 2.4 +/- 1.0 for adipose tissue. The AUC(0-24) ratios for free gemifloxacin in tissues to the MIC at which 90% of frequently isolated bacteria are inhibited were close to or higher than 100 h. Therefore, based on pharmacokinetic and pharmacodynamic calculations, we conclude that gemifloxacin might be a useful therapeutic option for the treatment of soft tissue infections. PMID:15504848

  10. Concentrations of Gemifloxacin at the Target Site in Healthy Volunteers after a Single Oral Dose

    PubMed Central

    Islinger, Florian; Bouw, Rene; Stahl, Mathias; Lackner, Edith; Zeleny, Petra; Brunner, Martin; Müller, Markus; Eichler, Hans Georg; Joukhadar, Christian

    2004-01-01

    Free gemifloxacin concentrations in the interstitial space fluid of skeletal muscle and subcutaneous adipose tissue were measured by means of in vivo microdialysis to characterize the ability of gemifloxacin to penetrate human soft tissues. Twelve healthy volunteers received a single oral dose of 320 mg of gemifloxacin. The mean areas under the concentration-time curves from 0 to 10 h (AUC0-10) were significantly higher for soft tissue than for unbound gemifloxacin in plasma (P < 0.05). The ratios of the mean AUC0-10 for tissue to the AUC0-10 for free gemifloxacin in plasma were 1.7 ± 0.7 (mean ± standard deviation) for skeletal muscle and 2.4 ± 1.0 for adipose tissue. The AUC0-24 ratios for free gemifloxacin in tissues to the MIC at which 90% of frequently isolated bacteria are inhibited were close to or higher than 100 h. Therefore, based on pharmacokinetic and pharmacodynamic calculations, we conclude that gemifloxacin might be a useful therapeutic option for the treatment of soft tissue infections. PMID:15504848

  11. Validation of G6PD Point-of-Care Tests among Healthy Volunteers in Yangon, Myanmar

    PubMed Central

    Maw, Lwin Zar; Chowwiwat, Nongnud; Bansil, Pooja; Domingo, Gonzalo J.; Htun, Moh Moh; Thant, Kyaw Zin; Htut, Ye; Nosten, Francois

    2016-01-01

    Primaquine and other 8-amnoquinoline based anti-malarials can cause haemolysis in subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Correct diagnosis of G6PD status in patients is crucial for safe treatment of both relapsing stages of Plasmodium vivax and transmitting forms of Plasmodium falciparum. Lack of suitable point-of-care tests has hampered a much needed wide use of primaquine for malaria elimination. In this study we have assessed the performances of two qualitative tests, the fluorescent spot test (FST) and the G6PD CareStart test (CST), against the gold standard quantitative spectrophotometric assay in a population of 1000 random adult healthy volunteers living in Yangon, Myanmar. The prevalence of G6PD deficiency in the Bamar, Karen and in the whole sample set was 6.6% (10.1% in males), 9.2% (21.0% in males) and 6.8% (11.1% in males) respectively. The FST and CST showed comparable performances with sensitivity over 95% and specificity over 90%, however for cases with severe G6PD activity the FTS had improved performance. If used with a conservative interpretation of the signal, the CareStart test has the potential to be used in the field and, by allowing a wider use of primaquine, to help malaria elimination. PMID:27035821

  12. Pharmacokinetics and bioequivalence of two trimebutine formulations in healthy volunteers using desmethyl-trimebutine levels.

    PubMed

    Saivin, S; Lavit, M; Michel, F; Labaune, J P; Martin, A; Cahiez, G; Donazzolo, C; Chomard, J M; Houin, G

    2000-08-01

    Trimebutine tablets (dimethylamino-2-phenyl-2-n-butyl-3,4,5- trimethoxybenzoate maleate, CAS 34140-59-5, reference) and a new tablet formulation (Eurogalena, test) were administered in 24 healthy volunteers of both sexes according to a cross-over design, in a single dose of one 100 mg tablet of each formulation. Blood samples were drawn off over a 24-h period, before (time 0) and after each administration at specific intervals. Trimebutine and its main active metabolite, desmethyl-trimebutine, were measured in plasma using a validated HPLC method with UV detection. For both compounds, the sensitivity was 20 ng.ml-1 and the analytical method was proved to be linear for concentrations between 20 ng.ml-1 and 5000 ng.ml-1, with a variability less than 11%. The non-compartmental method was used for pharmacokinetic analysis. The confidence interval approach was used for comparison of the formulations according to the EU guidance note on bioavailability and bioequivalence on Cmax, AUC0-t and AUC0-infinity, log transformed. Tmax values were statistically compared using the Friedman non-parametric test. No trimebutine concentration was measured in the plasma samples. The obtained data with desmethyl-trimebutine proved the bioequivalence of the two tested formulations. PMID:10994155

  13. Cannabis use is associated with increased CCL11 plasma levels in young healthy volunteers.

    PubMed

    Fernandez-Egea, Emilio; Scoriels, Linda; Theegala, Swathi; Giro, Maria; Ozanne, Susan E; Burling, Keith; Jones, Peter B

    2013-10-01

    Cannabis is a widely used recreational drug. Its effect on human health and psychosis remains controversial. In this study, we aimed to explore the possibility that cannabis use influenced CCL11 plasma levels. Increased CCL11 chemokine has been reported in schizophrenia and cannabis is a known trigger of schizophrenia. Additionally, plasma levels of the chemokine CCL11 have recently been shown to increase with age and with cognitive deficits and hippocampal neurogenesis. For this study, a total of 87 healthy volunteers (68% men, age range 18-35 years) completed the Cannabis Experience Questionnaire that included information on sociodemographic and morphometric data and provided a blood sample for CCL11 measurement. 'Current users' of cannabis (n=18) had significantly higher CCL11 plasma levels compared to 'past users' (n=33) and 'never users' (n=36) [F(3,84)=3.649; p=0.030]. The latter two groups had similar CCL11 levels. Higher CCL11 plasma levels could not be attributed to gender, age, body mass index, physical activity or use of other legal/illegal drugs. These results suggest that cannabis use increases CCL11 plasma levels and the effects are reversible when cannabis use ceases. PMID:23820464

  14. Influence of food on the tyramine pressor effect during chronic moclobemide treatment of healthy volunteers.

    PubMed

    Audebert, C; Blin, O; Monjanel-Mouterde, S; Auquier, P; Pedarriosse, A M; Dingemanse, J; Durand, A; Cano, J P

    1992-01-01

    An open study was carried out to examine the effect of moclobemide, a new antidepressant reversible inhibitor of MAO-A, on the pressor response induced by oral tyramine added to meals of different lipid and protein composition, and to correlate the blood pressure increase in the tyramine test with that obtained during an exercise test. Eight healthy volunteers of both sexes participated in the study. A tyramine sensitivity and an exercise test were performed beforehand. Subjects were included if, under fasting condition, their systolic blood pressure (SBP) increased by more than 30 mmHg after administration of 400 or 600 mg tyramine. Exercise tests were performed to determine the grade of effort that corresponded to a rise in SBP of 30 mmHg. Subjects received moclobemide 600 mg/d. Starting on Day 7, each subject consumed a standardized meal (52 g lipids, 43 g proteins, 86 g carbohydrates) just before taking moclobemide. Tyramine was added to these meals in daily increasing doses of 50, 100, 150...mg until an increase in SBP > or = 30 mmHg was obtained. On moclobemide treatment, an average dose of 250 mg tyramine (range 150-400 mg) increased SBP by 36.6 mmHg. The time to reach peak SBP was longer (175 min) than in the fasting condition before the trial (40.6 min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1483487

  15. Cannabis use is associated with increased CCL11 plasma levels in young healthy volunteers.

    PubMed

    Fernandez-Egea, Emilio; Scoriels, Linda; Theegala, Swathi; Giro, Maria; Ozanne, Susan E; Burling, Keith; Jones, Peter B

    2013-10-01

    Cannabis is a widely used recreational drug. Its effect on human health and psychosis remains controversial. In this study, we aimed to explore the possibility that cannabis use influenced CCL11 plasma levels. Increased CCL11 chemokine has been reported in schizophrenia and cannabis is a known trigger of schizophrenia. Additionally, plasma levels of the chemokine CCL11 have recently been shown to increase with age and with cognitive deficits and hippocampal neurogenesis. For this study, a total of 87 healthy volunteers (68% men, age range 18-35 years) completed the Cannabis Experience Questionnaire that included information on sociodemographic and morphometric data and provided a blood sample for CCL11 measurement. 'Current users' of cannabis (n=18) had significantly higher CCL11 plasma levels compared to 'past users' (n=33) and 'never users' (n=36) [F(3,84)=3.649; p=0.030]. The latter two groups had similar CCL11 levels. Higher CCL11 plasma levels could not be attributed to gender, age, body mass index, physical activity or use of other legal/illegal drugs. These results suggest that cannabis use increases CCL11 plasma levels and the effects are reversible when cannabis use ceases.

  16. Bioavailability of an R-α-Lipoic Acid/γ-Cyclodextrin Complex in Healthy Volunteers.

    PubMed

    Ikuta, Naoko; Okamoto, Hinako; Furune, Takahiro; Uekaji, Yukiko; Terao, Keiji; Uchida, Ryota; Iwamoto, Kosuke; Miyajima, Atsushi; Hirota, Takashi; Sakamoto, Norihiro

    2016-06-15

    R-α-lipoic acid (R-LA) is a cofactor of mitochondrial enzymes and a very strong antioxidant. R-LA is available as a functional food ingredient but is unstable against heat or acid. Stabilized R-LA was prepared through complexation with γ-cyclodextrin (CD), yielding R-LA/CD. R-LA/CD was orally administered to six healthy volunteers and showed higher plasma levels with an area under the plasma concentration-time curve that was 2.5 times higher than that after oral administration of non-complexed R-LA, although the time to reach the maximum plasma concentration and half-life did not differ. Furthermore, the plasma glucose level after a single oral administration of R-LA/CD or R-LA was not affected and no side effects were observed. These results indicate that R-LA/CD could be easily absorbed in the intestine. In conclusion, γ-CD complexation is a promising technology for delivering functional but unstable ingredients like R-LA.

  17. Effect of caffeine on lower esophageal sphincter pressure in Thai healthy volunteers.

    PubMed

    Lohsiriwat, S; Puengna, N; Leelakusolvong, S

    2006-01-01

    Caffeine affects many aspects of body function including the gastrointestinal system. A single-blinded experimental study was performed to evaluate the effect of caffeine on lower esophageal sphincter (LES) and esophageal peristaltic contractions in healthy Thai adults. The volunteers were six men and six women aged 19-31 years. Subjects drank 100 mL of water. Five wet swallows were performed 30 min after the drink. The basal LES pressure was continuously measured using esophageal manometric technique. They then consumed another 100 mL of water containing caffeine at the dose of 3.5 mg/kg body weight. The swallows and basal LES pressure monitoring were repeated. The results showed no change in basal LES pressure after a water drink while caffeine consumption significantly lowered the pressure at 10, 15, 20 and 25 min. The mean amplitude of contractions and peristaltic velocity were decreased at the distal esophagus at 3 and 8 cm above LES. The mean duration of contraction was decreased at the distal part but increased at the more proximal esophagus. The heart rate, systolic and diastolic blood pressures were increased significantly at 10-20 min after caffeine ingestion. This study indicated that caffeine 3.5 mg/kg affected esophageal function, resulting in a decrease in basal LES pressure and distal esophageal contraction, which is known to promote the reflux of gastric contents up into the esophagus.

  18. Pharmacokinetics and bioequivalence evaluation of leflunomide tablets in Korean healthy volunteers.

    PubMed

    Lim, Y-J; Shim, E-J; Kim, H-S; Oh, M; Shon, J-H; Shin, J-G; Moon, B-S; Song, G-S; Kim, E-Y

    2013-12-01

    Leflunomide is a disease-modifying antirheumatic drug. The purpose of this study was to evaluate the bioequivalence of a test drug (CJ leflunomide) and a commercially available reference drug (Arava®) at 2 doses (10 and 20 mg) in healthy Korean volunteers. This was a single-dose (28 individuals enrolled at each dose group), randomized, open-label, 2-way crossover study. The 2 treatment periods were separated by a 56-day wash-out interval. Blood sampling was conducted until 672 h after drug administration. Plasma teriflunomide (active metabolite of leflunomide) concentrations were determined, and pharmacokinetic parameters were calculated. Bioequivalence was evaluated using an ANOVA model, based on the AUCt and the Cmax after administration of leflunomide tablets. Bioequivalence was defined as the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of AUCt and Cmax for the test and reference drugs being within the range of 0.80-1.25. The GMRs (90% CI) for AUCt and Cmax were 0.9506 (0.9091-0.9941) and 0.9861 (0.9360-1.0389), respectively, in the 10 mg study, and 0.9524 (0.9101-0.9968) and 0.9740 (0.9314-1.0186), respectively, in the 20 mg study. The 90% CIs of AUCt and Cmax at each dose were within the accepted range for bioequivalence. Based on the results, the test drug (CJ leflunomide) was bioequivalent to the commercially available reference drug (Arava®) at both doses. PMID:23884659

  19. Lung Delivery of Indacaterol and Mometasone Furoate Following Inhalation of QMF149 in Healthy Volunteers.

    PubMed

    Vaidya, Soniya S; Khindri, Sanjeev; Maahs, Suzanne; Machineni, Surendra; Hara, Hisanori; Juan, Axel; Kaiser, Günther

    2016-07-01

    This single-dose, 4-period crossover study evaluated the pharmacokinetics (PK) of the β2 -agonist indacaterol maleate and the corticosteroid mometasone furoate (MF) after inhalation of a fixed-dose combination (QMF149, indacaterol maleate/MF, 500/400 μg) via the Twisthaler (TH) device with and without activated charcoal and postdose mouth rinsing in healthy volunteers. The PK of indacaterol maleate 300 μg inhaled via the Breezhaler (BRZ) device was also characterized. Relative bioavailability of indacaterol and MF for inhalation with versus without charcoal, based on AUClast, was 0.25 (90% confidence interval [CI], 0.18-0.35) and 0.70 (90%CI, 0.52-0.93), respectively. Thus, 25% and 70% of systemic exposure of indacaterol and MF, respectively was due to pulmonary absorption and 75% and 30%, respectively, was due to gastrointestinal absorption. Mouth rinsing reduced the systemic exposure of indacaterol by approximately 35% but had no relevant effect on the exposure of MF. Dose-normalized AUClast for indacaterol inhaled via the BRZ device was 2.3-fold higher than QMF149 via the TH device. All treatments had a good safety profile and were well tolerated. Data from this study and comparison with inhalation of indacaterol via the BRZ device suggest that the latter was more efficient than the TH device regarding lung delivery of indacaterol. PMID:27310329

  20. The effects of exercise and body armor on cognitive function in healthy volunteers.

    PubMed

    Roberts, Aaron P J; Cole, Jon C

    2013-05-01

    Police officers routinely wear body armor to protect themselves against the threat posed by firearms and edged weapons, yet little is known of the cognitive effects of doing so. Two studies investigated the effects of exercise and body armor on working memory function in healthy volunteers. In study 1, male undergraduates were assigned to one of four groups: (i) brief exercise, (ii) brief exercise wearing body armor, (iii) extended exercise, and (iv) extended exercise wearing body armor. In study 2, university gym members were assigned to one of two groups: (i) wearing body armor and (ii) not wearing body armor. In both studies, heart rate and oral temperature were measured before, immediately after, and 5 minutes after exercise. The phonemic verbal fluency task and digits backward test were administered at the same time points. In both studies, a mixed analysis of variance revealed statistically significant changes to the cognitive functioning of participants. A change in cognitive strategy was observed, reflected by a decrease in executive function (switches) and an increase in nonexecutive function (cluster size). These data suggest that the cognitive effects of exercise and body armor may have profound implications for police officers' ability to make tactical decisions. PMID:23756004

  1. Pharmacokinetic comparison of the vasorelaxant compound ferulic acid following the administration of Guanxin II to healthy volunteers and patients with angina pectoris.

    PubMed

    Li, Yun-Hui; Huang, Xi; Wang, Yang; Fan, Rong; Zhang, Hong-Min; Ren, Ping; Chen, Yao; Zhou, Hong-Hao; Liu, Zhao-Qian; Liang, Yi-Zeng; Lu, Hong-Mei

    2013-11-01

    Coronary heart disease (CHD) is the leading cause of mortality worldwide. The Chinese medicinal formula Guanxin II has been shown to have a favorable effect in the attenuation of angina. The aim of this study was to compare the pharmacokinetics of ferulic acid (FA), which is a vasorelaxant compound present in Guanxin II, in healthy volunteers and patients with angina pectoris following the administration of Guanxin II. Ex vivo experiments were performed in order to investigate the vasorelaxant effect of FA on the human internal mammary artery (IMA) to provide evidence that it is a bioactive component of Guanxin II. Following the oral administration of Guanxin II, the FA levels in the serum were quantified by a simple and rapid high-performance liquid chromatography (HPLC) method. Treatment with FA (10(-8)-10(-3) M) caused a concentration-dependent relaxation of endothelial IMA rings following precontraction with KCl. Statistically significant differences were identified between the pharmaco-kinetic parameters Cmax, t1/2α, t1/2β and t1/2Ka of the healthy volunteers and the patients with angina pectoris following the oral administration of Guanxin II. FA is a bioactive compound absorbed from Guanxin II that attenuates angina pectoris, a condition that may modify the pharmacokinetics of FA. Not only do the pharmacokinetic parameters direct the clinical use of Guanxin II, but they may also be useful for exploring the pathology of angina pectoris.

  2. Amount of mpl on bone marrow haemopoietic precursor cells from healthy volunteers and patients with refractory anaemia.

    PubMed

    Takeshita, A; Shinjo, K; Naito, K; Nakamura, S; Izumi, M; Ling, P; Ohnishi, K; Ohno, R

    1997-12-01

    Using a non-isotopic ligand binding assay using multi-colour flow cytometry, we quantitatively examined the amount of mpl in megakaryocyte-platelet lineage cells. Firstly, we quantified the amount of mpl on cell lines. Mpl gene-transfected BaF3 cells expressed a large amount of mpl, whereas original BaF3, K562, HL-60 and NOMO-1 cells showed no mpl. In bone marrow cells from healthy volunteers, mpl was expressed on CD34+ cells from the very early stage of differentiation when they had no CD38 antigen. The amount of mpl increased with differentiation to CD34+ CD41+ cells, but decreased with further differentiation to CD34- CD41+ cells. In CD34+ CD41+ cells the amount of mpl varied according to cell size: abundant in large cells, moderate in medium-size cells and a little in small cells. In bone marrow cells from patients with refractory anaemia (RA), the amount of mpl was decreased compared with that in bone marrow cells from healthy volunteers. When analysed by the same CD phenotype and same cell size, the amount of mpl was less in RA patients compared with that in healthy volunteers in all phenotypes and sizes tested. The proportion of large CD34+ CD41+ cells was less in RA patients than in normal volunteers. PMID:9432017

  3. Normal Solid Gastric Emptying Values Measured by Scintigraphy Using Asian-style Meal:A Multicenter Study in Healthy Volunteers

    PubMed Central

    Vasavid, Pataramon; Chaiwatanarat, Tawatchai; Pusuwan, Pawana; Sritara, Chanika; Roysri, Krisana; Namwongprom, Sirianong; Kuanrakcharoen, Pichit; Premprabha, Teerapon; Chunlertrith, Kitti; Thongsawat, Satawat; Sirinthornpunya, Siam; Ovartlarnporn, Bancha; Kachintorn, Udom; Leelakusolvong, Somchai; Kositchaiwat, Chomsri; Chakkaphak, Suriya; Gonlachanvit, Sutep

    2014-01-01

    Background/Aims To report gastric emptying scintigraphy, normal values should be established for a specific protocol. The aim of this study was to provide normal gastric emptying values and determine factors affecting gastric emptying using Asian rice-based meal in healthy volunteers. Methods One hundred and ninety-two healthy volunteers were included at 7 tertiary care centers across Thailand. Gastric emptying scintigraphy was acquired in 45 degree left anterior oblique view immediately after ingestion of a 267 kcal steamed-rice with technetium-99m labeled-microwaved egg meal with 100 mL water for up to 4 hours. Results One hundred and eighty-nine volunteers (99 females, age 43 ± 14 years) completed the study. The medians (5–95th percentiles) of lag time, gastric emptying half time (GE T1/2) and percent gastric retentions at 2 and 4 hours for all volunteers were 18.6 (0.5–39.1) minutes, 68.7 (45.1–107.8) minutes, 16.3% (2.7–49.8%) and 1.1% (0.2–8.8%), respectively. Female volunteers had significantly slower gastric emptying compared to male (GE T1/2, 74 [48–115] minutes vs. 63 (41–96) minutes; P < 0.05). Female volunteers who were in luteal phase of menstrual cycle had significantly slower gastric emptying compared to those in follicular phase or menopausal status (GE T1/2, 85 [66–102] mintes vs. 69 [50–120] minutes or 72 [47–109] minutes, P < 0.05). All of smoking volunteers were male. Smoker male volunteers had significantly faster gastric emptying compared to non-smoker males (GE T1/2, 56 [44–80] minutes vs. 67 [44–100] minutes, P < 0.05). Age, body mass index and alcohol consumption habits did not affect gastric emptying values. Conclusions A steamed-rice with microwaved egg meal was well tolerated by healthy volunteers. Gender, menstrual status and smoking status were found to affect solid gastric emptying. PMID:24948129

  4. Effect of Slow and Fast Pranayama Training on Handgrip Strength and Endurance in Healthy Volunteers

    PubMed Central

    Thangavel, Dinesh; Gaur, Girwar Singh; Bhavanani, Ananda Balayogi; Rajajeyakumar, M.; Syam, Sunder A.

    2014-01-01

    Background: Pranayama has been assigned very important role in yogic system of exercises and is said to be much more important than yogasanas for keeping sound health. Also different pranayamas produce divergent physiological effects. Aim: To study the effect of 12 weeks training of slow and fast pranayama on handgrip strength and endurance in young, healthy volunteers of JIPMER population. Settings and Design: Present study was conducted in the Department of Physiology, JIPMER in 2011-12 (1.06.11 to 1.04.12). Materials and Methods: Total of 91 volunteer subjects were randomised into slow pranayama (SPG) (n=29), fast pranayama (FPG) (n=32) and control groups (CG) (n=30). Supervised pranayama training (SPG - Nadisodhana, Pranav pranayama and Savitri pranayama; FPG - Kapalabhati, Bhastrika and Kukkuriya pranayama) was given for 30 minutes thrice a week for 12 weeks to both slow and fast pranayama groups by certified yoga trainer. Hand grip strength (HGS) and endurance (HGE) parameters were recorded using handgrip dynamometer (Rolex, India) at baseline and after 12 weeks of pranayama training. Statistical Analysis Used: Longitudinal changes in each group were compared by using Student’s paired t-test. Delta changes in each group were analysed by ANOVA with Tukey post-hoc analysis. Results: In SPG significant improvement occurred only in HGE parameter from 83.95±45.06 to 101.62±53.87 (seconds) (p<0.001) whereas in FPG, significant improvement was observed in HGS from 33.31±9.83 to 37.9±9.41 (Kilograms) (p=0.01) as well as in HGE from 92.78±41.37 to 116.56±58.54 (seconds) (p=0.004). Using Students unpaired t-test difference between the groups in HGS is found to be 1.17±5.485 in SPG and in FPG is 4.59±7.26 (p=0.39); HGE difference in SPG is 1.77±21.17 and in FPG is 2.38±43.27 (p>0.05). Conclusion: Pranayama training decreases sympathetic activity, resulting in mental relaxation and decreased autonomic arousal thereby, decreasing force fluctuations during

  5. Cutaneous Respirometry as Novel Technique to Monitor Mitochondrial Function: A Feasibility Study in Healthy Volunteers

    PubMed Central

    Stolker, Robert Jan; Mik, Egbert

    2016-01-01

    Background The protoporphyrin IX-triplet state lifetime technique (PpIX-TSLT) is proposed as a potential clinical non-invasive tool to monitor mitochondrial function. This technique has been evaluated in several animal studies. Mitochondrial respirometry allows measurement in vivo of mitochondrial oxygen tension (mitoPO2) and mitochondrial oxygen consumption (mitoVO2) in skin. This study describes the first use of a clinical prototype in skin of humans. Methods The clinical prototype was tested in 30 healthy volunteers. A self-adhesive patch containing 2 mg 5-aminolevulinic acid (ALA) was applied on the skin of the anterior chest wall (sternal) for induction of mitochondrial protoporphyrin IX and was protected from light for 5 h. MitoPO2 was measured by means of oxygen-dependent delayed fluorescence of protoporphyrin IX. MitoVO2 was determined by dynamic mitoPO2 measurements on the primed skin, while locally blocking oxygen supply by applying local pressure with the measurement probe. MitoPO2 was recorded before and during a 60-s period of compression of the microcirculation, at an interval of 1 Hz. Oxygen consumption (i.e. the local oxygen disappearance rate) was calculated from the decay of the mitoPO2 slope. Results Oxygen-dependent delayed fluorescence measurements were successfully performed in the skin of 27 volunteers. The average value (± SD) of mitoPO2 was 44 ± 17 mmHg and mean mitoVO2 values were 5.8 ± 2.3 and 6.1 ± 1.6 mmHg s-1 at a skin temperature of 34°C and 40°C, respectively. No major discomfort during measurement and no long-term dermatological abnormalities were reported in a survey performed 1 month after measurements. Conclusion These results show that the clinical prototype allows measurement of mitochondrial oxygenation and oxygen consumption in humans. The development of this clinically applicable device offers opportunities for further evaluation of the technique in humans and the start of first clinical studies. PMID:27455073

  6. Phosphatidylethanol in blood as a marker of ethanol consumption in healthy volunteers: comparison with other markers.

    PubMed

    Varga, A; Hansson, P; Lundqvist, C; Alling, C

    1998-11-01

    Phosphatidylethanol is a "pathological" phospholipid, formed via the action of phospholipase D only in the presence of ethanol. The present study was made to elucidate how different levels and patterns of alcohol intake affect blood levels of phosphatidylethanol in comparison with other markers of abuse. We used a new HPLC-evaporative light-scattering detection technique for phosphatidylethanol quantitation. This method had a total coefficient of variation of <20% at the detection limit of 0.2 nmol, equaling 0.8 micromol/liter of whole blood. Two groups were studied. (a) Five healthy volunteers were given 32 to 47 g of ethanol in a single dose, to give blood ethanol levels of approximately 25 mmol/liter after 30 to 60 min. Phosphatidylethanol, carbohydrate-deficient transferrin (CDT), and blood ethanol were measured before and after the intake. (b) Twelve student volunteers were studied during a 3 week period of prolonged alcohol consumption (total estimated intake: 1334 +/- 488 g, mean +/- SD) and phosphatidylethanol, serum-CDT, gamma-glutamyltransferase, and blood ethanol were measured at the start of the period (day 1) and twice at the end of the period (days 18 and 21). In group (a), no phosphatidylethanol was detected at any time after ethanol dosage/intake. In group (b), no blood phosphatidylethanol or blood ethanol could be demonstrated at the start, and serum-CDT was below the discrimination limit (1.3%) in all persons. No phosphatidylethanol was detected in those four persons with the lowest intake (742 +/- 150 g). However, the remaining eight persons had detectable levels of phosphatidylethanol (1.0 to 2.1 micromol/liter), and these had a higher total intake (1630 +/- 389 g). There was a statistically significant (p = 0.02) increase in serum CDT for 3 weeks. However, only 3 of 12 persons increased above the discrimination limit. The present results indicate that a substantial alcohol intake is needed to elevate blood phosphatidylethanol. In comparison

  7. Investigation of cerebral haemodynamics by near-infrared spectroscopy in young healthy volunteers reveals posture-dependent spontaneous oscillations.

    PubMed

    Tachtsidis, Ilias; Elwell, Clare E; Leung, Terence S; Lee, Chuen-Wai; Smith, Martin; Delpy, David T

    2004-04-01

    Autonomic reflexes enable the cardiovascular system to respond to gravitational displacement of blood during changes in posture. Spontaneous oscillations present in the cerebral and systemic circulation of healthy subjects have demonstrated a regulatory role. This study assessed the dynamic responses of the cerebral and systemic circulation upon standing up and the posture dependence of spontaneous oscillations. In ten young healthy volunteers, blood pressure and cerebral haemodynamics were continuously monitored non-invasively using the Portapres and near-infrared spectroscopy (NIRS), respectively. Oscillatory changes in the cerebral NIRS signals and the diastolic blood pressure (DBP) signal have been identified by the fast Fourier analysis. Blood pressure increased during standing and returned to basal level when volunteers sat on a chair. The mean value of cerebral tissue oxygen index (TOI) as measured by NIRS did not demonstrate any significant changes. Oscillatory changes in DBP, oxyhaemoglobin concentration [O2Hb] and TOI showed a significant increase when subjects were standing. Investigation of the low frequency component (approximately 0.1 Hz) of these fluctuations revealed posture dependence associated with activation of autonomic reflexes. Systemic and cerebral changes appeared to preserve adequate blood flow and cerebral perfusion during standing in healthy volunteers. Oscillatory changes in [O2Hb] and TOI, which may be related to the degree of cerebral sympathetic stimulation, are posture dependent in healthy subjects. PMID:15132309

  8. Using “Clinical Trial Diaries” to Track Patterns of Participation for Serial Healthy Volunteers in U.S. Phase I Studies

    PubMed Central

    Edelblute, Heather B.; Fisher, Jill A.

    2015-01-01

    Phase I testing of investigational drugs relies on healthy volunteers as research participants. Many U.S. healthy volunteers enroll repeatedly in clinical trials for the financial compensation. Serial participants are incentivized to ignore restrictions on their participation, and no centralized clinical trial registry prevents dual enrollment. Little is currently known about how healthy volunteers participate in studies over time, hampering the development of policies to protect this group. We detail a methodology developed as part of a longitudinal study to track in real-time healthy volunteers’ Phase I participation. Illustrating these data through three case studies, we document how healthy volunteers use strategies, such as qualifying for studies at more than one clinic and traveling significant distances, to maximize their participation. Our findings suggest that “clinical trial diaries” can generate critical information about serial research participation and point to ethical issues unique to healthy volunteers’ involvement in Phase I clinical trials. PMID:25742668

  9. Brain Targeted Transcranial Administration of Diazepam and Shortening of Sleep Latency in Healthy Human Volunteers

    PubMed Central

    Pathirana, W.; Gunasekera, S. M.; Constantine, G. R.; Perera, Sanja; Perera, B. M.; Kamaladiwela, R.

    2011-01-01

    Application of medicated oils on scalp had been practiced for centuries in the Ayurvedic system of medicine in diseases associated with the central nervous system. It is possible that the effectiveness of the therapy may be a result of targeted delivery of active compounds to the brain transcranially. Evidence also comes from two previous studies with positive results on brain targeted transcranial delivery of methadone base and diazepam on rat models. Possibility of transcranial drug delivery was investigated in healthy human volunteers using electroencephalography techniques by assessing the ability of transcranially administered diazepam in bringing about β activity in the electroencephalographic wave patterns and shortening of the sleep latency period. Non polar drug molecules dissolved in a non-aqueous sesame oil based vehicle is a significant feature in the transcranial dosage design. The study was under taken in two phases. In the Phase-I study scalp application of a single dose of 2 mg/3 ml of the oil was employed and in the Phase-II study repeat application of three doses 24 h apart were employed. Sleep latency changes were monitored with Multiple Sleep Latency Tests with 5 naps employing the standard electroencephalography, electroocculography and electromyography electrodes. Sleep onset was identified with the first epoch of any sleep stage non rapid eye movement 1, 2, 3, 4 or rapid eye movement using electroencephalography, electroocculography and electromyography criteria. In both phases of the study there was significant reduction in the sleep latencies. It was much more pronounced in the Phase-II study. None of the subjects however displayed beta activity in the electroencephalography. Sleep latency reduction following scalp application in both the phases are suggestive of transcranial migration of diazepam molecules to the receptor sites of the nerve tissue of the brain eliciting its pharmacological effect of sedation. Transcranial brain targeted

  10. Cerebral venous blood oxygenation monitoring during hyperventilation in healthy volunteers with a novel optoacoustic system

    NASA Astrophysics Data System (ADS)

    Petrov, Andrey; Prough, Donald S.; Petrov, Irene Y.; Petrov, Yuriy; Deyo, Donald J.; Henkel, Sheryl N.; Seeton, Roger; Esenaliev, Rinat O.

    2013-03-01

    Monitoring of cerebral venous oxygenation is useful to facilitate management of patients with severe or moderate traumatic brain injury (TBI). Prompt recognition of low cerebral venous oxygenation is a key to avoiding secondary brain injury associated with brain hypoxia. In specialized clinical research centers, jugular venous bulb catheters have been used for cerebral venous oxygenation monitoring and have demonstrated that oxygen saturation < 50% (normal range is 55-75%) correlates with poor clinical outcome. We developed an optoacoustic technique for noninvasive monitoring of cerebral venous oxygenation. Recently, we designed and built a novel, medical grade optoacoustic system operating in the near-infrared spectral range for continuous, real-time oxygenation monitoring in the superior sagittal sinus (SSS), a large central cerebral vein. In this work, we designed and built a novel SSS optoacoustic probe and developed a new algorithm for SSS oxygenation measurement. The SSS signals were measured in healthy volunteers during voluntary hyperventilation, which induced changes in SSS oxygenation. Simultaneously, we measured exhaled carbon dioxide concentration (EtCO2) using capnography. Good temporal correlation between decreases in optoacoustically measured SSS oxygenation and decreases in EtCO2 was obtained. Decreases in EtCO2 from normal values (35-45 mmHg) to 20-25 mmHg resulted in SSS oxygenation decreases by 3-10%. Intersubject variability of the responses may relate to nonspecific brain activation associated with voluntary hyperventilation. The obtained data demonstrate the capability of the optoacoustic system to detect in real time minor changes in the SSS blood oxygenation.

  11. Acute biochemical variations induced by four different calcium salts in healthy male volunteers.

    PubMed

    Reginster, J Y; Denis, D; Bartsch, V; Deroisy, R; Zegels, B; Franchimont, P

    1993-09-01

    Calcium (Ca) supplements have positive effects in growing children, reduce bone loss in late-postmenopausal women with a low calcium diet and, in association with vitamin D3 supplements, may reduce non-vertebral fracture rates in elderly women. However, for many formulated pharmaceutical products their relative beneficial effects have not been conclusively established. We have compared the acute (6 h) metabolic responses following oral administration of two preparations of calcium gluconolactate and carbonate (CG and CG'), tricalcium phosphate (TCP) and calcium citrate (CC), given on separate occasions in each of 10 healthy young male volunteers. The subjects fasted overnight for 12 h and continued to fast during the experimental procedure. A 1000 mg dose of each Ca salt was ingested at weekly intervals. Blood was drawn after 30, 60, 90, 120, 180, 240, 300 and 360 min for measurement of serum Ca, phosphorus (P), parathyroid hormone (PTH) and whole plasma calcitonin (iCT). All Ca supplements induced significant (+6.4% to +8.1%; p < 0.01) increases in Ca and significant suppression of PTH (-37.4% to -57.4%; p < 0.01). Comparison of response curves revealed significantly (p < 0.01) more marked Ca increase and PTH suppression with CC than with the other three Ca salts. CG' and CC induced marginal decreases in serum P and the overall curve of P variations was different for TCP compared with CG, CG' and CC. No significant variation of iCT was recorded during the test.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Brain areas activated by uncertain reward-based decision-making in healthy volunteers.

    PubMed

    Guo, Zongjun; Chen, Juan; Liu, Shien; Li, Yuhuan; Sun, Bo; Gao, Zhenbo

    2013-12-15

    Reward-based decision-making has been found to activate several brain areas, including the ventrolateral prefrontal lobe, orbitofrontal cortex, anterior cingulate cortex, ventral striatum, and mesolimbic dopaminergic system. In this study, we observed brain areas activated under three degrees of uncertainty in a reward-based decision-making task (certain, risky, and ambiguous). The tasks were presented using a brain function audiovisual stimulation system. We conducted brain scans of 15 healthy volunteers using a 3.0T magnetic resonance scanner. We used SPM8 to analyze the location and intensity of activation during the reward-based decision-making task, with respect to the three conditions. We found that the orbitofrontal cortex was activated in the certain reward condition, while the prefrontal cortex, precentral gyrus, occipital visual cortex, inferior parietal lobe, cerebellar posterior lobe, middle temporal gyrus, inferior temporal gyrus, limbic lobe, and midbrain were activated during the 'risk' condition. The prefrontal cortex, temporal pole, inferior temporal gyrus, occipital visual cortex, and cerebellar posterior lobe were activated during ambiguous decision-making. The ventrolateral prefrontal lobe, frontal pole of the prefrontal lobe, orbitofrontal cortex, precentral gyrus, inferior temporal gyrus, fusiform gyrus, supramarginal gyrus, inferior parietal lobule, and cerebellar posterior lobe exhibited greater activation in the 'risk' than in the 'certain' condition (P < 0.05). The frontal pole and dorsolateral region of the prefrontal lobe, as well as the cerebellar posterior lobe, showed significantly greater activation in the 'ambiguous' condition compared to the 'risk' condition (P < 0.05). The prefrontal lobe, occipital lobe, parietal lobe, temporal lobe, limbic lobe, midbrain, and posterior lobe of the cerebellum were activated during decision-making about uncertain rewards. Thus, we observed different levels and regions of activation for different

  13. Pharmacokinetic, partial pharmacodynamic and initial safety analysis of (-)-epicatechin in healthy volunteers.

    PubMed

    Barnett, Christopher F; Moreno-Ulloa, Aldo; Shiva, Sruti; Ramirez-Sanchez, Israel; Taub, Pam R; Su, Yongxuan; Ceballos, Guillermo; Dugar, Sundeep; Schreiner, George; Villarreal, Francisco

    2015-03-01

    (-)-Epicatechin ((-)-EPI), a naturally occurring flavanol, has emerged as a likely candidate for cocoa-based product reported reductions in cardiometabolic risk. The present study aimed to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of purified (-)-EPI administered to healthy volunteers. In this phase I, open-label, two-part single- and multiple-dose study, subjects received either a single dose (n = 9) of 50, 100 or 200 mg or multiple doses (n = 8) of 50 mg daily (q.d.) or twice daily (b.i.d) for 5 days. Blood was collected at 0, 0.5, 1, 2, 4 and 6 h after (-)-EPI administration in the single and multiple dose groups (blood collection repeated in day 5). Samples were analyzed by HPLC-HR-ESI-MS for EPI and metabolite quantification. In the q.d. and b.i.d. groups, blood samples were analyzed for NO surrogates and follistatin levels as well as, platelet mitochondrial complexes I, V and citrate synthase activity levels. (-)-EPI was well tolerated and readily absorbed with further phase 2 metabolism. On day 5, in the q.d. and b.i.d. groups, there were significant increases in plasma nitrite of 30% and 17%, respectively. In the q.d. group on day 5 vs. day 1, platelet mitochondrial complexes I, IV and citrate synthase activities demonstrated a significant increase of ∼92, 62 and 8%, respectively. Average day 5 follistatin AUC levels were ∼2.5 fold higher vs. day 1 AUC levels in the b.i.d. group. (-)-EPI was safe to use, with no observed adverse effects, and our findings suggest that increases in NO metabolites, mitochondrial enzyme function and plasma follistatin levels may underlie some of the beneficial effects of cocoa products or (-)-EPI as reported in other studies. PMID:25598082

  14. Effect of ginkgo biloba on the pharmacokinetics of raltegravir in healthy volunteers.

    PubMed

    Blonk, Maren; Colbers, Angela; Poirters, Anne; Schouwenberg, Bas; Burger, David

    2012-10-01

    Medicinal herbs may cause clinically relevant drug interactions with antiretroviral agents. Ginkgo biloba extract is a popular herbal product among HIV-infected patients because of its positive effects on cognitive function. Raltegravir, an HIV integrase inhibitor, is increasingly being used as part of combined antiretroviral therapy. Clinical data on the potential inhibitory or inductive effect of ginkgo biloba on the pharmacokinetics of raltegravir were lacking, and concomitant use was not recommended. We studied the effect of ginkgo biloba extract on the pharmacokinetics of raltegravir in an open-label, randomized, two-period, crossover phase I trial in 18 healthy volunteers. Subjects were randomly assigned to a regimen of 120 mg of ginkgo biloba twice daily for 15 days plus a single dose of raltegravir (400 mg) on day 15, a washout period, and 400 mg of raltegravir on day 36 or the test and reference treatments in reverse order. Pharmacokinetic sampling of raltegravir was performed up to 12 h after intake on an empty stomach. All subjects (9 male) completed the trial, and no serious adverse events were reported. Geometric mean ratios (90% confidence intervals) of the area under the plasma concentration-time curve from dosing to infinity (AUC(0-∞)) and the maximum plasma concentration (C(max)) of raltegravir with ginkgo biloba versus raltegravir alone were 1.21 (0.93 to 1.58) and 1.44 (1.03 to 2.02). Ginkgo biloba did not reduce raltegravir exposure. The potential increase in the C(max) of raltegravir is probably of minor importance, given the large intersubject variability of raltegravir pharmacokinetics and its reported safety profile.

  15. Effect of Fast and Slow Pranayama Practice on Cognitive Functions In Healthy Volunteers

    PubMed Central

    Sharma, Vivek Kumar; M., Rajajeyakumar; S., Velkumary; Subramanian, Senthil Kumar; Bhavanani, Ananda B.; Madanmohan; Sahai, Ajit; Thangavel, Dinesh

    2014-01-01

    Objectives: To compare the cumulative effect of commonly practised slow and fast pranayama on cognitive functions in healthy volunteers. Settings and Design: 84 participants who were in self-reported good health, who were in the age group of 18-25 years, who were randomized to fast pranayama, slow pranayama and control group with 28 participants in each group. Material and Methods: Fast pranayama included kapalabhati, bhastrika and kukkuriya. Slow pranayama included nadishodhana, Pranav and Savitri. Respective pranayama training was given for 35 minutes, three times per week, for a duration of 12 weeks under the supervision of a certified yoga trainer. Parameters were recorded before and after 12 weeks of intervention: Perceived stress scale (PSS), BMI, waist to hip ratio and cognitive parameters-letter cancellation test, trail making tests A and B, forward and reverse digit spans and auditory and visual reaction times for red light and green light. Statistical Analysis: Inter–group comparison was done by one way ANOVA and intra-group comparison was done by paired t-test. Results and Conclusion: Executive functions, PSS and reaction time improved significantly in both fast and slow pranayama groups, except reverse digit span, which showed an improvement only in fast pranayama group. In addition, percentage reduction in reaction time was significantly more in the fast pranayama group as compared to that in slow pranayama group. Both types of pranayamas are beneficial for cognitive functions, but fast pranayama has additional effects on executive function of manipulation in auditory working memory, central neural processing and sensory-motor performance. PMID:24596711

  16. Dopamine cross-sensitization between psychostimulant drugs and stress in healthy male volunteers

    PubMed Central

    Booij, L; Welfeld, K; Leyton, M; Dagher, A; Boileau, I; Sibon, I; Baker, G B; Diksic, M; Soucy, J-P; Pruessner, J C; Cawley-Fiset, E; Casey, K F; Benkelfat, C

    2016-01-01

    Dysregulation of the stress response system is a potential etiological factor in the development of and relapse to multiple neuropsychiatric disorders. Previously we reported that repeated intermittent d-amphetamine administration can lead to progressively greater dopamine release, thereby providing evidence of drug-induced neurochemical sensitization. Here, we test the hypothesis that repeated exposure to d-amphetamine increases dopaminergic responses to stress; that is, produces cross-sensitization. Using positron emission tomography, we measured in 17 healthy male volunteers (mean±s.d.=22.1±3.4 years) [11C]raclopride binding responses to a validated psychosocial stress task before and 2 weeks after a regimen of repeated d-amphetamine (3 × 0.3 mg kg−1, by mouth; n=8) or placebo (3 × lactose, by mouth; n=9). Mood and physiological measurements were recorded throughout each session. Before the d-amphetamine regimen, exposure to the stress task increased behavioral and physiological indices of stress (anxiety, heart rate, cortisol, all P⩽0.05). Following the d-amphetamine regimen, the stress-induced cortisol responses were augmented (P<0.04), and voxel-based analyses showed larger stress-induced decreases in [11C]raclopride non-displaceable binding potential across the striatum. In the placebo group, re-exposure to stress led to smaller clusters of decreased [11C]raclopride binding, primarily in the sensorimotor striatum (P<0.05). Together, this study provides evidence for drug × stress cross-sensitization; moreover, random exposure to stimulants and/or stress cumulatively, while enhancing dopamine release in striatal areas, may contribute to a lowered set point for psychopathologies in which altered dopamine neurotransmission is invoked. PMID:26905412

  17. Comparative bioavailability study of two cefixime formulations administered orally in healthy male volunteers.

    PubMed

    Zakeri-Milani, Parvin; Valizadeh, Hadi; Islambulchilar, Ziba

    2008-01-01

    The bioavailability of a new cefixime ((6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-(carboxymethoxyimino) acetamido]-8-oxo-3-vinyl-5-thia-1-azabicyclo-[4,2,0]-oct-2-ene-2-carboxylic acid, CAS 79350-37-1) tablet preparation (Loprax) was compared with that of a reference preparation of the drug in 24 healthy male volunteers. The trial was designed as an open, randomized, single-blind, two-sequence, two-period crossover study. Under fasting conditions, each subject received a single oral dose of 400 mg cefixime tablet as a test or reference formulation on 2 treatment days. The treatment periods were separated by a one-week washout period. The plasma concentrations of the drug were analyzed by a rapid and sensitive HPLC method with UV detection. The pharmacokinetic parameters included AUC0-24h, AUC0-infinity, Cmax, t1/2, and Ke. The mean AUC0-infinity of cefixime was 45008.7 +/- 10989.9 and 45221.3 +/- 2155.7 n x h/ml for the test and reference formulation, respectively. The maximum plasma concentration (Cmax) of cefixime was on average 4746.9 +/- 1284 ng/ml for the test and 4726.3 +/- 1206.9 ng/ml for the reference product. No statistical differences were observed for Cmax and the area under the plasma concentration-time curve for test and reference tablets. The calculated 90% confidence intervals based on the ANOVA analysis for the mean test/reference ratios of Cmax, AUC0-infinity and AUC0-24h of cefixime were in the bioequivalence range (94%-112%). Therefore, the two formulations were considered to be bioequivalent.

  18. Distribution kinetics of enoxacin and its metabolite oxoenoxacin in excretory fluids of healthy volunteers.

    PubMed Central

    Jaehde, U; Sörgel, F; Naber, K G; Zürcher, J; Schunack, W

    1995-01-01

    The distribution kinetics of enoxacin and its main metabolite oxoenoxacin in excretory fluids was investigated in 11 healthy volunteers. A single intravenous dose of 428 mg of enoxacin was given as a 1-h infusion. Serial samples of plasma, urine, saliva, nasal secretions, tears, and sweat were drawn and analyzed for enoxacin and oxoenoxacin by reversed-phase high-pressure liquid chromatography. Large differences in the concentration-time profiles of the excretory fluids analyzed were observed. Nasal secretions exhibited the highest enoxacin exposure, as assessed by the area under the concentration-time curve. Excretory fluid/plasma area under the concentration-time curve ratios were found to be 1.67 +/- 0.36 for nasal secretions, 0.76 +/- 0.28 for saliva, 0.25 +/- 0.07 for sweat, and 0.23 +/- 0.11 for tears. The elimination half-life of enoxacin from sweat (8.27 +/- 2.63 h) was significantly longer than that for plasma (5.10 +/- 0.46 h). Oxoenoxacin was detected in urine and saliva and exhibited a higher renal clearance and a lower saliva exposure than the parent compound. In contrast to that of the metabolite, distribution of enoxacin in saliva was found to be time and pH dependent. In conclusion, our study revealed considerable differences in the distribution kinetics of enoxacin among various excretory sites. Because of distinct acidic and basic properties, the anionic oxometabolite significantly differs from the zwitterionic parent compound in its distribution characteristics. PMID:8540722

  19. First clinical experience with TRV130: pharmacokinetics and pharmacodynamics in healthy volunteers.

    PubMed

    Soergel, David G; Subach, Ruth Ann; Sadler, Brian; Connell, John; Marion, Alan S; Cowan, Conrad L; Violin, Jonathan D; Lark, Michael W

    2014-03-01

    TRV130 is a G protein-biased ligand at the µ-opioid receptor. In preclinical studies it was potently analgesic while causing less respiratory depression and gastrointestinal dysfunction than morphine, suggesting unique benefits in acute pain management. A first-in-human study was conducted with ascending doses of TRV130 to explore its tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteers. TRV130 was well-tolerated over the dose range 0.15 to 7 mg administered intravenously over 1 hour. TRV130 geometric mean exposure and Cmax were dose-linear, with AUC0-inf of 2.52 to 205.97 ng h/mL and Cmax of 1.04 to 102.36 ng/mL across the dose range tested, with half-life of 1.6-2.7 hours. A 1.5 mg dose of TRV130 was also well-tolerated when administered as 30, 15, 5, and 1 minute infusions. TRV130 pharmacokinetics were modestly affected by CYP2D6 phenotype: clearance was reduced by 53% in CYP2D6 poor metabolizers.TRV130 caused dose- and exposure-related pupil constriction, confirming central compartment µ-opioid receptor engagement. Marked pupil constriction was noted at 2.2, 4, and 7 mg doses. Nausea and vomiting observed at the 7 mg dose limited further dose escalation. These findings suggest that TRV130 may have a broad margin between doses causing µ-opioid receptor-mediated pharmacology and doses causing µ-opioid receptor-mediated intolerance. PMID:24122908

  20. Microbiome Changes in Healthy Volunteers Treated with GSK1322322, a Novel Antibiotic Targeting Bacterial Peptide Deformylase

    PubMed Central

    Arat, Seda; Spivak, Aaron; Van Horn, Stephanie; Thomas, Elizabeth; Traini, Christopher; Sathe, Ganesh; Livi, George P.; Ingraham, Karen; Jones, Lori; Aubart, Kelly; Holmes, David J.; Naderer, Odin

    2014-01-01

    GSK1322322 is a novel antibacterial agent under development, and it has known antibacterial activities against multidrug-resistant respiratory and skin pathogens through its inhibition of the bacterial peptide deformylase. Here, we used next-generation sequencing (NGS) of the bacterial 16S rRNA genes from stool samples collected from 61 healthy volunteers at the predosing and end-of-study time points to determine the effects of GSK1322322 on the gastrointestinal (GI) microbiota in a phase I, randomized, double-blind, and placebo-controlled study. GSK1322322 was administered either intravenously (i.v.) only or in an oral-i.v. combination in single- and repeat-dose-escalation infusions. Analysis of the 16S rRNA sequence data found no significant changes in the relative abundances of GI operational taxonomic units (OTUs) between the prestudy and end-of-study samples for either the placebo- or i.v.-only-treated subjects. However, oral-i.v. treatment resulted in significant decreases in some bacterial taxa, the Firmicutes and Bacteroidales, and increases in others, the Betaproteobacteria, Gammaproteobacteria, and Bifidobacteriaceae. Microbiome diversity plots clearly differentiated the end-of-study oral-i.v.-dosed samples from all others collected. The changes in genome function as inferred from species composition suggest an increase in bacterial transporter and xenobiotic metabolism pathways in these samples. A phylogenetic analysis of the peptide deformylase protein sequences collected from the published genomes of clinical isolates previously tested for GSK1322322 in vitro susceptibility and GI bacterial reference genomes suggests that antibiotic target homology is one of several factors that influences the response of GI microbiota to this antibiotic. Our study shows that dosing regimen and target class are important factors when considering the impact of antibiotic usage on GI microbiota. (This clinical trial was registered at the GlaxoSmithKline Clinical Study

  1. Acute biochemical variations induced by four different calcium salts in healthy male volunteers.

    PubMed

    Reginster, J Y; Denis, D; Bartsch, V; Deroisy, R; Zegels, B; Franchimont, P

    1993-09-01

    Calcium (Ca) supplements have positive effects in growing children, reduce bone loss in late-postmenopausal women with a low calcium diet and, in association with vitamin D3 supplements, may reduce non-vertebral fracture rates in elderly women. However, for many formulated pharmaceutical products their relative beneficial effects have not been conclusively established. We have compared the acute (6 h) metabolic responses following oral administration of two preparations of calcium gluconolactate and carbonate (CG and CG'), tricalcium phosphate (TCP) and calcium citrate (CC), given on separate occasions in each of 10 healthy young male volunteers. The subjects fasted overnight for 12 h and continued to fast during the experimental procedure. A 1000 mg dose of each Ca salt was ingested at weekly intervals. Blood was drawn after 30, 60, 90, 120, 180, 240, 300 and 360 min for measurement of serum Ca, phosphorus (P), parathyroid hormone (PTH) and whole plasma calcitonin (iCT). All Ca supplements induced significant (+6.4% to +8.1%; p < 0.01) increases in Ca and significant suppression of PTH (-37.4% to -57.4%; p < 0.01). Comparison of response curves revealed significantly (p < 0.01) more marked Ca increase and PTH suppression with CC than with the other three Ca salts. CG' and CC induced marginal decreases in serum P and the overall curve of P variations was different for TCP compared with CG, CG' and CC. No significant variation of iCT was recorded during the test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8400610

  2. Detection of exhaled hydrogen sulphide gas in healthy human volunteers during intravenous administration of sodium sulphide

    PubMed Central

    Toombs, Christopher F; Insko, Michael A; Wintner, Edward A; Deckwerth, Thomas L; Usansky, Helen; Jamil, Khurram; Goldstein, Brahm; Cooreman, Michael; Szabo, Csaba

    2010-01-01

    INTRODUCTION Hydrogen sulphide (H2S) is an endogenous gaseous signaling molecule and potential therapeutic agent. Emerging studies indicate its therapeutic potential in a variety of cardiovascular diseases and in critical illness. Augmentation of endogenous sulphide concentrations by intravenous administration of sodium sulphide can be used for the delivery of H2S to the tissues. In the current study, we have measured H2S concentrations in the exhaled breath of healthy human volunteers subjected to increasing doses sodium sulphide in a human phase I safety and tolerability study. METHODS We have measured reactive sulphide in the blood via ex vivo derivatization of sulphide with monobromobimane to form sulphide-dibimane and blood concentrations of thiosulfate (major oxidative metabolite of sulphide) via ion chromatography. We have measured exhaled H2S concentrations using a custom-made device based on a sulphide gas detector (Interscan). RESULTS Administration of IK-1001, a parenteral formulation of Na2S (0.005–0.20 mg kg−1, i.v., infused over 1 min) induced an elevation of blood sulphide and thiosulfate concentrations over baseline, which was observed within the first 1–5 min following administration of IK-1001 at 0.10 mg kg−1 dose and higher. In all subjects, basal exhaled H2S was observed to be higher than the ambient concentration of H2S gas in room air, indicative of on-going endogenous H2S production in human subjects. Upon intravenous administration of Na2S, a rapid elevation of exhaled H2S concentrations was observed. The amount of exhaled H2S rapidly decreased after discontinuation of the infusion of Na2S. CONCLUSION Exhaled H2S represents a detectable route of elimination after parenteral administration of Na2S. PMID:20565454

  3. Acute psychomotor effects of MDMA and ethanol (co-) administration over time in healthy volunteers.

    PubMed

    Dumont, G J H; Schoemaker, R C; Touw, D J; Sweep, F C G J; Buitelaar, J K; van Gerven, J M A; Verkes, R J

    2010-02-01

    In Western societies, a considerable percentage of young people use 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy'). The use of alcohol (ethanol) in combination with ecstasy is common. The aim of the present study was to assess the acute psychomotor and subjective effects of (co-) administration of MDMA and ethanol over time and in relation to the pharmacokinetics. We performed a four-way, double blind, randomized, crossover, placebo-controlled study in 16 healthy volunteers (nine men, seven women) between the ages of 18 and 29. MDMA (100 mg) was given orally while blood alcohol concentration was maintained at pseudo-steady state levels of approximately 0.6 per thousand for 3 h by a 10% intravenous ethanol clamp. MDMA significantly increased psychomotor speed but did not affect psychomotor accuracy and induced subjective arousal. Ethanol impaired both psychomotor speed and accuracy and induced sedation. Coadministration of ethanol and MDMA improved psychomotor speed but impaired psychomotor accuracy compared with placebo and reversed ethanol-induced sedation. Pharmacokinetics and pharmacodynamics showed maximal effects at 90-150 min after MDMA administration after which drug effects declined in spite of persisting MDMA plasma concentration, with the exception of ethanol-induced sedation, which manifested itself fully only after the infusion was stopped. In conclusion, results show that subjects were more aroused when intoxicated with both substances combined compared with placebo, but psychomotor accuracy was significantly impaired. These findings may have implications for general neuropsychological functioning as this may provide a sense of adequate performance that does not agree with a significant reduction in psychomotor accuracy.

  4. The pharmacokinetic profile of crocetin in healthy adult human volunteers after a single oral administration.

    PubMed

    Umigai, N; Murakami, K; Ulit, M V; Antonio, L S; Shirotori, M; Morikawa, H; Nakano, T

    2011-05-15

    Crocetin, a unique carotenoid with a short carbon chain length, is an active compound of saffron and Gardenia jasminoides Ellis used as traditional herbal medicine. The present study was undertaken to investigate the pharmacokinetic profiles of crocetin in healthy adult subjects. The study was conducted as an open-label, single dose escalation with 10 Filipino volunteers (5 men and 5 women). The subjects received a single dose of crocetin at three doses (7.5, 15 and 22.5 mg) in one week interval. Blood samples were collected from the brachial vein before and at 1, 2, 4, 6, 8, 10 and 24 h after administration. Plasma concentrations of crocetin were determined by high-performance liquid chromatography (HPLC). Crocetin was rapidly absorbed and detected within an hour of administration with a mean time to reach maximum concentration (T(max)) of crocetin ranging from 4.0 to 4.8 h. The mean values of C(max) and AUC(0-24h) ranged from 100.9 to 279.7 ng/ml and 556.5 to 1720.8 ng. h/ml respectively. C(max) and AUC values increased with dose proportional manner. Crocetin was eliminated from human plasma with a mean elimination half life (T(½) of 6.1 to 7.5 h. In summary, there were no serious adverse events up to 22.5 mg dose of crocetin while crocetin was found to be absorbed more quickly than the other carotenoids such as β-carotene, lutein and lycopene. PMID:21112749

  5. Distribution kinetics of enoxacin and its metabolite oxoenoxacin in excretory fluids of healthy volunteers.

    PubMed

    Jaehde, U; Sörgel, F; Naber, K G; Zürcher, J; Schunack, W

    1995-09-01

    The distribution kinetics of enoxacin and its main metabolite oxoenoxacin in excretory fluids was investigated in 11 healthy volunteers. A single intravenous dose of 428 mg of enoxacin was given as a 1-h infusion. Serial samples of plasma, urine, saliva, nasal secretions, tears, and sweat were drawn and analyzed for enoxacin and oxoenoxacin by reversed-phase high-pressure liquid chromatography. Large differences in the concentration-time profiles of the excretory fluids analyzed were observed. Nasal secretions exhibited the highest enoxacin exposure, as assessed by the area under the concentration-time curve. Excretory fluid/plasma area under the concentration-time curve ratios were found to be 1.67 +/- 0.36 for nasal secretions, 0.76 +/- 0.28 for saliva, 0.25 +/- 0.07 for sweat, and 0.23 +/- 0.11 for tears. The elimination half-life of enoxacin from sweat (8.27 +/- 2.63 h) was significantly longer than that for plasma (5.10 +/- 0.46 h). Oxoenoxacin was detected in urine and saliva and exhibited a higher renal clearance and a lower saliva exposure than the parent compound. In contrast to that of the metabolite, distribution of enoxacin in saliva was found to be time and pH dependent. In conclusion, our study revealed considerable differences in the distribution kinetics of enoxacin among various excretory sites. Because of distinct acidic and basic properties, the anionic oxometabolite significantly differs from the zwitterionic parent compound in its distribution characteristics.

  6. Full Spectrum of LPS Activation in Alveolar Macrophages of Healthy Volunteers by Whole Transcriptomic Profiling

    PubMed Central

    Zhao, Yutong; Zhao, Jing; Donahoe, Michael P.; Barge, Suchitra; Horne, William T.; Kolls, Jay K.; McVerry, Bryan J.; Birukova, Anastasiya; Tighe, Robert M.; Foster, W. Michael; Hollingsworth, John; Ray, Anuradha; Mallampalli, Rama; Ray, Prabir; Lee, Janet S.

    2016-01-01

    Despite recent advances in understanding macrophage activation, little is known regarding how human alveolar macrophages in health calibrate its transcriptional response to canonical TLR4 activation. In this study, we examined the full spectrum of LPS activation and determined whether the transcriptomic profile of human alveolar macrophages is distinguished by a TIR-domain-containing adapter-inducing interferon-β (TRIF)-dominant type I interferon signature. Bronchoalveolar lavage macrophages were obtained from healthy volunteers, stimulated in the presence or absence of ultrapure LPS in vitro, and whole transcriptomic profiling was performed by RNA sequencing (RNA-Seq). LPS induced a robust type I interferon transcriptional response and Ingenuity Pathway Analysis predicted interferon regulatory factor (IRF)7 as the top upstream regulator of 89 known gene targets. Ubiquitin-specific peptidase (USP)-18, a negative regulator of interferon α/β responses, was among the top up-regulated genes in addition to IL10 and USP41, a novel gene with no known biological function but with high sequence homology to USP18. We determined whether IRF-7 and USP-18 can influence downstream macrophage effector cytokine production such as IL-10. We show that IRF-7 siRNA knockdown enhanced LPS-induced IL-10 production in human monocyte-derived macrophages, and USP-18 overexpression attenuated LPS-induced production of IL-10 in RAW264.7 cells. Quantitative PCR confirmed upregulation of USP18, USP41, IL10, and IRF7. An independent cohort confirmed LPS induction of USP41 and IL10 genes. These results suggest that IRF-7 and predicted downstream target USP18, both elements of a type I interferon gene signature identified by RNA-Seq, may serve to fine-tune early cytokine response by calibrating IL-10 production in human alveolar macrophages. PMID:27434537

  7. First clinical experience with TRV130: pharmacokinetics and pharmacodynamics in healthy volunteers.

    PubMed

    Soergel, David G; Subach, Ruth Ann; Sadler, Brian; Connell, John; Marion, Alan S; Cowan, Conrad L; Violin, Jonathan D; Lark, Michael W

    2014-03-01

    TRV130 is a G protein-biased ligand at the µ-opioid receptor. In preclinical studies it was potently analgesic while causing less respiratory depression and gastrointestinal dysfunction than morphine, suggesting unique benefits in acute pain management. A first-in-human study was conducted with ascending doses of TRV130 to explore its tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteers. TRV130 was well-tolerated over the dose range 0.15 to 7 mg administered intravenously over 1 hour. TRV130 geometric mean exposure and Cmax were dose-linear, with AUC0-inf of 2.52 to 205.97 ng h/mL and Cmax of 1.04 to 102.36 ng/mL across the dose range tested, with half-life of 1.6-2.7 hours. A 1.5 mg dose of TRV130 was also well-tolerated when administered as 30, 15, 5, and 1 minute infusions. TRV130 pharmacokinetics were modestly affected by CYP2D6 phenotype: clearance was reduced by 53% in CYP2D6 poor metabolizers.TRV130 caused dose- and exposure-related pupil constriction, confirming central compartment µ-opioid receptor engagement. Marked pupil constriction was noted at 2.2, 4, and 7 mg doses. Nausea and vomiting observed at the 7 mg dose limited further dose escalation. These findings suggest that TRV130 may have a broad margin between doses causing µ-opioid receptor-mediated pharmacology and doses causing µ-opioid receptor-mediated intolerance.

  8. Bioavailability study of dronabinol oral solution versus dronabinol capsules in healthy volunteers

    PubMed Central

    Parikh, Neha; Kramer, William G; Khurana, Varun; Cognata Smith, Christina; Vetticaden, Santosh

    2016-01-01

    Background Dronabinol, a pharmaceutical Δ-9-tetrahydrocannabinol, was originally developed as an oral capsule. This study evaluated the bioavailability of a new formulation, dronabinol oral solution, versus a dronabinol capsule formulation. Methods In an open-label, four-period, single-dose, crossover study, healthy volunteers were randomly assigned to one of two treatment sequences (T-R-T-R and R-T-R-T; T = dronabinol 4.25 mg oral solution and R = dronabinol 5 mg capsule) under fasted conditions, with a minimum 7-day washout period between doses. Analyses were performed on venous blood samples drawn 15 minutes to 48 hours postdose, and dronabinol concentrations were assayed by liquid chromatography–tandem mass spectrometry. Results Fifty-one of 52 individuals had pharmacokinetic data for analysis. The 90% confidence interval of the geometric mean ratio (oral solution/capsule) for dronabinol was within the 80%–125% bioequivalence range for area under the plasma concentration–time curve (AUC) from time zero to last measurable concentration (AUC0–t) and AUC from time zero to infinity (AUC0–∞). Maximum plasma concentration was also bioequivalent for the two dronabinol formulations. Intraindividual variability in AUC0–∞ was >60% lower for dronabinol oral solution 4.25 mg versus dronabinol capsule 5 mg. Plasma dronabinol concentrations were detected within 15 minutes postdose in 100% of patients when receiving oral solution and in <25% of patients when receiving capsules. Conclusion Single-dose dronabinol oral solution 4.25 mg was bioequivalent to dronabinol capsule 5 mg under fasted conditions. Dronabinol oral solution formulation may provide an easy-to-swallow administration option with lower intraindividual variability as well as more rapid absorption versus dronabinol capsules. PMID:27785111

  9. Haemodynamic effects of hyperbaric hyperoxia in healthy volunteers: an echocardiographic and Doppler study.

    PubMed

    Molénat, Florence; Boussuges, Alain; Grandfond, Aliocha; Rostain, Jean-Claude; Sainty, Jean-Marie; Robinet, Claude; Galland, François; Meliet, Jean Louis

    2004-04-01

    In the present study, we observed the haemodynamic changes, using echocardiography and Doppler, in ten healthy volunteers during 6 h of compression in a hyperbaric chamber with a protocol designed to reproduce the conditions as near as possible to a real dive. Ambient pressure varied from 1.6 to 3 atm (1 atm=101.325 kPa) and partial pressure of inspired O2 from 1.2 to 2.8 atm. Subjects performed periods of exercise with breathing through a closed-circuit self-contained underwater breathing apparatus (SCUBA). Subjects did not eat or drink during the study. Examinations were performed after 15 min and 5 h. After 15 min, stroke volume (SV), left atrial (LA) diameter and left ventricular (LV) end-diastolic diameter (LVEDD) decreased. Heart rate (HR) and cardiac output (CO) did not vary, but indices of the LV systolic performance decreased by 10% and the LV meridional wall stress increased by 17%. After 5 h, although weight decreased, the serum protein concentration increased. Compared with values obtained after 15 min, SV and CO decreased, but LV systolic performance, LA diameter, LVEDD and LV meridional wall stress remained unchanged. Compared with the reference values obtained at sea level, total arterial compliance decreased, HR remained unchanged and CO decreased. In conclusion, hyperbaric hyperoxia results in significant haemodynamic changes. Initially, hyperoxia and the SCUBA system are responsible for reducing LV preload, increasing LV afterload and decreasing LV systolic performance, although CO did not change. Prolonged exposure resulted in a further decrease in LV preload, because of dehydration, and in a further increase in LV afterload, due to systemic vasoconstriction, with the consequence of decreasing CO.

  10. Effects of acute hypoventilation and hyperventilation on exhaled carbon monoxide measurement in healthy volunteers

    PubMed Central

    2009-01-01

    Background High levels of exhaled carbon monoxide (eCO) are a marker of airway or lung inflammation. We investigated whether hypo- or hyperventilation can affect measured values. Methods Ten healthy volunteers were trained to achieve sustained end-tidal CO2 (etCO2) concentrations of 30 (hyperventilation), 40 (normoventilation), and 50 mmHg (hypoventilation). As soon as target etCO2 values were achieved for 120 sec, exhaled breath was analyzed for eCO with a photoacoustic spectrometer. At etCO2 values of 30 and 40 mmHg exhaled breath was sampled both after a deep inspiration and after a normal one. All measurements were performed in two different environmental conditions: A) ambient CO concentration = 0.8 ppm and B) ambient CO concentration = 1.7 ppm. Results During normoventilation, eCO mean (standard deviation) was 11.5 (0.8) ppm; it decreased to 10.3 (0.8) ppm during hyperventilation (p < 0.01) and increased to 11.9 (0.8) ppm during hypoventilation (p < 0.01). eCO changes were less pronounced than the correspondent etCO2 changes (hyperventilation: 10% Vs 25% decrease; hypoventilation 3% Vs 25% increase). Taking a deep inspiration before breath sampling was associated with lower eCO values (p < 0.01), while environmental CO levels did not affect eCO measurement. Conclusions eCO measurements should not be performed during marked acute hyperventilation, like that induced in this study, but the influence of less pronounced hyperventilation or of hypoventilation is probably negligible in clinical practice PMID:20030802

  11. Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study.

    PubMed

    Chow, H-H Sherry; Garland, Linda L; Hsu, Chiu-Hsieh; Vining, Donna R; Chew, Wade M; Miller, Jessica A; Perloff, Marjorie; Crowell, James A; Alberts, David S

    2010-09-01

    Resveratrol has been shown to exhibit cancer-preventive activities in preclinical studies. We conducted a clinical study to determine the effect of pharmacologic doses of resveratrol on drug- and carcinogen-metabolizing enzymes. Forty-two healthy volunteers underwent baseline assessment of cytochrome P450 (CYP) and phase II detoxification enzymes. CYP1A2, CYP2D6, CYP2C9, and CYP3A4 enzyme activities were measured by the metabolism of caffeine, dextromethorphan, losartan, and buspirone, respectively. Blood lymphocyte glutathione S-transferase (GST) activity and GST-pi level and serum total and direct bilirubin, a surrogate for UDP-glucuronosyl transferase (UGT) 1A1 activity, were measured to assess phase II enzymes. After the baseline evaluation, study participants took 1 g of resveratrol once daily for 4 weeks. Enzyme assessment was repeated upon intervention completion. Resveratrol intervention was found to inhibit the phenotypic indices of CYP3A4, CYP2D6, and CYP2C9 and to induce the phenotypic index of 1A2. Overall, GST and UGT1A1 activities were minimally affected by the intervention, although an induction of GST-pi level and UGT1A1 activity was observed in individuals with low baseline enzyme level/activity. We conclude that resveratrol can modulate enzyme systems involved in carcinogen activation and detoxification, which may be one mechanism by which resveratrol inhibits carcinogenesis. However, pharmacologic doses of resveratrol could potentially lead to increased adverse drug reactions or altered drug efficacy due to inhibition or induction of certain CYPs. Further clinical development of resveratrol for cancer prevention should consider evaluation of lower doses of resveratrol to minimize adverse metabolic drug interactions. PMID:20716633

  12. Glycine transporter type 1 occupancy by bitopertin: a positron emission tomography study in healthy volunteers.

    PubMed

    Martin-Facklam, Meret; Pizzagalli, Flavia; Zhou, Yun; Ostrowitzki, Susanne; Raymont, Vanessa; Brašić, James R; Parkar, Nikhat; Umbricht, Daniel; Dannals, Robert F; Goldwater, Ron; Wong, Dean F

    2013-02-01

    Deficient N-methyl-D-aspartate (NMDA) receptor transmission is thought to underlie schizophrenia. An approach for normalizing glutamate neurotransmission by enhancing NMDA receptor transmission is to increase glycine availability by inhibiting the glycine transporter type 1 (GlyT1). This study investigated the relationship between the plasma concentration of the glycine reuptake inhibitor bitopertin (RG1678) and brain GlyT1 occupancy. Healthy male volunteers received up to 175 mg bitopertin once daily, for 10-12 days. Three positron emission tomography scans, preceded by a single intravenous infusion of ∼30 mCi [(11)C]RO5013853, were performed: at baseline, on the last day of bitopertin treatment, and 2 days after drug discontinuation. Eighteen subjects were enrolled. At baseline, regional volume of distribution (V(T)) values were highest in the pons, thalamus, and cerebellum (1.7-2.7 ml/cm(3)) and lowest in cortical areas (∼0.8 ml/cm(3)). V(T) values were reduced to a homogeneous level following administration of 175 mg bitopertin. Occupancy values derived by a two-tissue five-parameter (2T5P) model, a simplified reference tissue model (SRTM), and a pseudoreference tissue model (PRTM) were overall comparable. At steady state, the relationship between bitopertin plasma concentration and GlyT1 occupancy derived by the 2T5P model, SRTM, and PRTM exhibited an EC(50) of ∼190, ∼200, and ∼130 ng/ml, respectively. E(max) was ∼92% independently of the model used. Bitopertin plasma concentration was a reliable predictor of occupancy because the concentration-occupancy relationship was superimposable at steady state and 2 days after drug discontinuation. These data allow understanding of the concentration-occupancy-efficacy relationship of bitopertin and support dose selection of future molecules. PMID:23132267

  13. Pharmacokinetics of pholcodine in healthy volunteers: single and chronic dosing studies.

    PubMed Central

    Chen, Z R; Bochner, F; Somogyi, A

    1988-01-01

    1. The pharmacokinetics of pholcodine after two single doses and after chronic administration were studied in healthy human volunteers. 2. Six subjects received single oral doses of 20 and 60 mg of pholcodine according to a balanced cross-over design with an interval of 3 weeks between the two treatments. Blood and saliva samples and all urine were collected over 168 h after each dosage administration. Subsequently, the same subjects received 20 mg pholcodine 8 hourly orally for 10 days. Blood and saliva samples and all urine were collected during an 8 h dosing interval after the last dose on day 11. 3. Plasma, saliva and urine concentrations of pholcodine were determined by a high performance liquid chromatographic assay. 4. After the single doses, pholcodine was absorbed rapidly (tmax = 1.6 +/- 1.2 h) and eliminated slowly with a mean half-life of 50.1 +/- 4.1 h. The renal clearance of pholcodine was 137 +/- 34 ml min-1 and was inversely correlated with urine pH (r = 0.60) but not with urine flow rate. 26.2 +/- 3.3% of the dose was excreted as unchanged pholcodine after both doses. The concentration of pholcodine in saliva was 3.6 times higher than in plasma. 5. After chronic administration, the pharmacokinetics of pholcodine were not statistically different from the single dose parameters. 6. Pholcodine did not appear to undergo conjugation. The plasma protein binding was 23.5%. Morphine, in unconjugated or conjugated form, was not detected in the urine of any subject after pholcodine administration. PMID:3190994

  14. Pharmacokinetics of daikenchuto, a traditional Japanese medicine (kampo) after single oral administration to healthy Japanese volunteers.

    PubMed

    Munekage, Masaya; Kitagawa, Hiroyuki; Ichikawa, Kengo; Watanabe, Junko; Aoki, Katsuyuki; Kono, Toru; Hanazaki, Kazuhiro

    2011-10-01

    The pharmacokinetics of daikenchuto (TJ-100), a pharmaceutical-grade traditional Japanese medicine, were investigated in healthy Japanese volunteers after a single oral administration of 2.5-, 5-, and 10-g doses. Six ingredients [hydroxy-α-sanshool (HAS), hydroxy-β-sanshool (HBS), [6]-shogaol (6S), [10]-shogaol (10S), ginsenoside Rb₁(GRB1), and ginsenoside Rg₁(GRG1)] of TJ-100 were determined by using liquid chromatography-tandem mass spectrometry. The results indicated that HAS, an ingredient derived from Zanthoxylum piperitum fruit, exhibited the highest plasma concentration among the six ingredients investigated. The plasma concentrations of HAS, HBS, 6S, and 10S reached the maximum concentration (approximately 400, 80, 0.14, and 0.6 ng/ml, respectively, after a 5-g administration of TJ-100) within 30 min after administration, and the mean half-life was approximately 2 h. Thus, these compounds were rapidly absorbed and eliminated. The plasma concentration of GRB1 reached the maximum concentration (2 ng/ml after a 5-g administration of TJ-100) at approximately 4 h after administration and the half-life of GRB1 was approximately 40 h. The plasma concentration of GRG1 was extremely low (<0.023 ng/ml). The pharmacokinetics of HAS, HBS, 6S, and 10S, were linear within the range of 2.5 to 10 g/day of TJ-100. On the other hand, the kinetics of GRB1 and GRG1 were not proportional to dosage, and plateauing was observed.

  15. Pharmacokinetic, partial pharmacodynamic and initial safety analysis of (−)-Epicatechin in healthy volunteers

    PubMed Central

    Barnett, Christopher F.; Moreno-Ulloa, Aldo; Shiva, Sruti; Ramirez-Sanchez, Israel; Taub, Pam R.; Su, Yongxuan; Ceballos, Guillermo; Dugar, Sundeep; Schreiner, George; Villarreal, Francisco

    2015-01-01

    (−)-Epicatechin ((−)-EPI), a naturally occurring flavanol has emerged as a likely candidate for cocoa-based product reported reductions in cardiometabolic risk. The present study aimed to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of purified (−)-EPI administered to healthy volunteers. In this phase I, open-label, two-part single- and multiple-dose study subjects received either a single dose (n=9) of 50, 100 or 200 mg or multiple doses (n=8) of 50 mg daily (q.d.) or twice daily (b.i.d) for 5 days. Blood was collected at 0, 0.5, 1, 2, 4 and 6 hrs after (−)-EPI administration in the single and multiple dose groups (blood collection repeated in day 5). Samples were analyzed by HPLC-HR-ESI-MS for EPI and metabolites quantification. In the q.d. and b.i.d. groups, blood samples were analyzed for NO surrogates, follistatin, platelet mitochondrial complex I, V and citrate synthase level determinations. (−)-EPI was well tolerated and readily absorbed with further phase 2 metabolism. On day 5, in the q.d. and b.i.d. groups, there were significant increases in plasma nitrite of 30 % and 17 %, respectively. In the q.d. group on day 5 vs. day 1, platelet mitochondria complexes I, IV and citrate synthase activities demonstrated a significant increase of ~ 92, 62 and 8 %, respectively. Average day 5 follistatin AUC levels were ~2.5 fold higher vs. day 1 AUC levels in the b.i.d. group. (−)-EPI was safe with no observed adverse effects and our findings suggest that increases in NO metabolites, mitochondrial enzyme function and plasma follistatin levels may underlie some of the beneficial effects of cocoa products or (−)-EPI as reported in other studies. PMID:25598082

  16. Flosequinan does not affect systemic and regional vascular responses to simulated orthostatic stress in healthy volunteers.

    PubMed Central

    Duranteau, J; Pussard, E; Edouard, A; Samii, K; Berdeaux, A; Giudicelli, J F

    1992-01-01

    1. The effects of a single oral dose (100 mg) of flosequinan on systemic and regional (forearm, splanchnic and renal) vascular responses to simulated orthostatic stress (lower body negative pressure, LBNP) were investigated in nine healthy male volunteers, in a double-blind, placebo-controlled crossover study. 2. Forty-five minutes after its administration and before LBNP, flosequinan induced a significant decrease in total peripheral and in forearm vascular resistances without any concomitant change in arterial pressure, in heart rate and in the investigated biological parameters (plasma catecholamines, arginine vasopressin and renin activity). 3. After flosequinan and placebo, LBNP induced similar decreases in central venous pressure at all levels of LBNP (-10, -20 and -40 mm Hg) and in pulse pressure at LBNP -40 mm Hg. LBNP-induced increase in forearm vascular resistance was significantly more marked after flosequinan than after placebo at all levels of LBNP, and this was also true for splanchnic vascular resistance but at LBNP -40 mm Hg only. However, inasmuch as the basal values of these two parameters before LBNP were lower after flosequinan than after placebo, their final values after LBNP -40 mm Hg were similar. Finally, LBNP-induced changes in renal vascular resistance, glomerular filtration rate and filtration fraction as well as in plasma catecholamines, arginine vasopressin and renin activity were similar after flosequinan and placebo at all levels of LBNP. 4. Flosequinan affected neither reflex control of heart rate (phenylephrine test) nor non-specific vasoconstrictor responses (cold pressor test). (ABSTRACT TRUNCATED AT 250 WORDS) PMID:1389945

  17. Pramipexole Increases Go Timeouts but Not No-go Errors in Healthy Volunteers

    PubMed Central

    Yang, Xue Qing; Glizer, Daniel; Vo, Andrew; Seergobin, Ken N.; MacDonald, Penny A.

    2016-01-01

    Parkinson’s disease (PD) is characterized by motor symptoms, such as resting tremor, bradykinesia and rigidity, but also features non-motor complications. PD patients taking dopaminergic therapy, such as levodopa but especially dopamine agonists (DAs), evidence an increase in impulse control disorders (ICDs), suggesting a link between dopaminergic therapy and impulsive pursuit of pleasurable activities. However, impulsivity is a multifaceted construct. Motor impulsivity refers to the inability to overcome automatic responses or cancel pre-potent responses. Previous research has suggested that PD patients, on dopaminergic medications, have decreased motor impulsivity. Whether effects on impulsivity are main effects of dopaminergic therapies or are specific to PD is unclear. Using a Go No-go task, we investigated the effect of a single dose of the DA pramipexole on motor impulsivity in healthy participants. The Go No-go task consisted of Go trials, for which keystroke responses were made as quickly as possible, and lesser frequency No-go trials, on which motor responses were to be inhibited. We hypothesized that pramipexole would decrease motor impulsivity. This would manifest as: (a) fewer No-go errors (i.e., fewer responses on trials in which a response ought to have been inhibited); and (b) more timed-out Go trials (i.e., more trials on which the deadline elapsed before a decision to make a keystroke occurred). Healthy volunteers were treated with either 0.5 mg of pramipexole or a standard placebo (randomly determined). During the 2-h wait period, they completed demographic, cognitive, physiological and affective measures. The pramipexole group had significantly more Go timeouts (p < 0.05) compared to the placebo group though they did not differ in percent of No-go errors. In contrast to its effect on pursuit of pleasurable activities, pramipexole did not increase motor impulsivity. In fact, in line with findings in PD and addiction, dopaminergic therapy might

  18. Effects of Sulpiride on True and False Memories of Thematically Related Pictures and Associated Words in Healthy Volunteers

    PubMed Central

    Guarnieri, Regina V.; Ribeiro, Rafaela L.; de Souza, Altay A. Lino; Galduróz, José Carlos F.; Covolan, Luciene; Bueno, Orlando F. A.

    2016-01-01

    Episodic memory, working memory, emotional memory, and attention are subject to dopaminergic modulation. However, the potential role of dopamine on the generation of false memories is unknown. This study defined the role of the dopamine D2 receptor on true and false recognition memories. Twenty-four young, healthy volunteers ingested a single dose of placebo or 400 mg oral sulpiride, a dopamine D2-receptor antagonist, just before starting the recognition memory task in a randomized, double-blind, and placebo-controlled trial. The sulpiride group presented more false recognitions during visual and verbal processing than the placebo group, although both groups had the same indices of true memory. These findings demonstrate that dopamine D2 receptors blockade in healthy volunteers can specifically increase the rate of false recognitions. The findings fit well the two-process view of causes of false memories, the activation/monitoring failures model. PMID:27047394

  19. The Area of Secondary Hyperalgesia following Heat Stimulation in Healthy Male Volunteers: Inter- and Intra-Individual Variance and Reproducibility

    PubMed Central

    Hansen, Morten Sejer; Wetterslev, Jørn; Pipper, Christian Bressen; Østervig, Rebecca; Asghar, Mohammad Sohail; Dahl, Jørgen Berg

    2016-01-01

    Introduction Clinical pain models can be applied when investigating basic physiologic pain responses in healthy volunteers. Several pain models exist; however, only few have been adequately validated. Our primary aim with this prospective study was to investigate the intra- and inter-individual variation in secondary hyperalgesia elicited by brief thermal sensitization (45°C for 3 min) in healthy volunteers. Material and Methods Fifty healthy volunteers were included. Areas of secondary hyperalgesia following brief thermal sensitization were investigated by 2 observers on 4 experimental days, with a minimum interval of 7 days. Additionally, heat pain detection threshold and pain during thermal stimulation (45°C for 1 min.), and the psychological tests Pain Catastrophizing Scale and Hospital Anxiety and Depression Score were applied. Results For areas of secondary hyperalgesia, an intra-observer intra-person correlation of 0.85, 95% CI [0.78, 0.90], an intra-observer inter-person correlation of 0.03, 95% CI [0.00, 0.16], and a coefficient of variation of 0.17, 95% CI [0.14, 0.21] was demonstrated. Four percent of the study population had areas of secondary hyperalgesia both below the 1st and above the 3rd quartile considering all included participants. Heat pain detection threshold predicted area of secondary hyperalgesia with an adjusted R2 of 0.20 (P = 0.0006). Conclusions We have demonstrated a low intra-individual, and a high inter-individual variation in thermally induced secondary hyperalgesia. We conclude that brief thermal sensitization produce secondary hyperalgesia with a high level of reproducibility, which can be applied to investigate different phenotypes related to secondary hyperalgesia in healthy volunteers. Trial Registration clinicaltrials.gov NCT02166164 PMID:27167119

  20. Nasal PMN response to repeated challenge with endotoxin in healthy volunteers**

    EPA Science Inventory

    Abstract Rationale: We have employed nasal challenge with Iipopolysaccharid (lPS) followed by nasal lavage (NU to experimentally induce and examine upper airway inflammation in human volunteers.It is unclear however whether adaptation within individuals occurs following repeated ...

  1. Effect of Tamarindus indica. L on the bioavailability of ibuprofen in healthy human volunteers.

    PubMed

    Garba, M; Yakasai, I A; Bakare, M T; Munir, H Y

    2003-01-01

    The influence of Tamarindus indica L fruit extract incorporated in a traditional meal on the bioavailability of Ibuprofen tablets 400 mg dose when given concurrently was studied in 6 healthy human volunteers. There was a statistically significant increase in the plasma levels of Ibuprofen and its metabolites hydroxy-ibuprofen and carboxy-ibuprofen respectively, when the meal containing Tamarindus indica fruit extract was administered with the ibuprofen tablets than when taken under fasting state or with the meal without the fruit extract. The C(max), AUC(0-6 hr) and Ka for ibuprofen increased from 38 +/- 0.70 microg/ml to 42 +/- 0.98 microg/ml (p > 0.05); and 28.03 +/- 2.40 microg/ml x hr to 56.51 +/- 0.16 microg/ml x hr (p < 0.05) and 1.048 +/- 0.02hr(-1) to 2.781 +/- 0.11 hr(-1) (p < 0.05) respectively. There was no change in the t(max) (120.00 +/- 0.43m) but there was a decrease in the k(el) from 0.63 +/- 0.20 hr(-1) to 0.46 +/- 0.11 hr(-1) (p<0.05). Similarly the C(max), AUC(0-6 h) and Ka for hydroxy-ibuprofen rose from 43 +/- 0.76 microg/ml to 45 +/- 0.16 microg/ml (p < 0.05); 39.04 +/- 2.30 microg/ml x hr to 59.49 +/- 2.39 microg/ml.hr in (p < 0.05) and 1.498 +/- 0.79hr(-1) to 3.442 +/- 0.23 hr(-1) (p < 0.05) respectively; while the C(max), AUC(0-6 h) and Ka for carboxy-ibuprofen rose from 48 +/- 0.7 microg/ml to 51 +/- 0.16 microg/ml (p < 0.05); 41.972 +/- 0.68 microg/ml x hr to 63.948 +/- 0.12 microg/ml x hr (p < 0.05) and 1.649 +/- 0.08 hr(-1) to 4.187 +/- 0.42 hr(-1) (p < 0.05) respectively. The study has indicated that Tamarindus indica L. fruit extract significantly increased the bioavailability of Ibuprofen.

  2. Chiral Plasma Pharmacokinetics and Urinary Excretion of Bupropion and Metabolites in Healthy Volunteers.

    PubMed

    Masters, Andrea R; Gufford, Brandon T; Lu, Jessica Bo Li; Metzger, Ingrid F; Jones, David R; Desta, Zeruesenay

    2016-08-01

    Bupropion, widely used as an antidepressant and smoking cessation aid, undergoes complex metabolism to yield numerous metabolites with unique disposition, effect, and drug-drug interactions (DDIs) in humans. The stereoselective plasma and urinary pharmacokinetics of bupropion and its metabolites were evaluated to understand their potential contributions to bupropion effects. Healthy human volunteers (n = 15) were administered a single oral dose of racemic bupropion (100 mg), which was followed by collection of plasma and urine samples and determination of bupropion and metabolite concentrations using novel liquid chromatography-tandem mass spectrometry assays. Time-dependent, elimination rate-limited, stereoselective pharmacokinetics were observed for all bupropion metabolites. Area under the plasma concentration-time curve from zero to infinity ratios were on average approximately 65, 6, 6, and 4 and Cmax ratios were approximately 35, 6, 3, and 0.5 for (2R,3R)-/(2S,3S)-hydroxybupropion, R-/S-bupropion, (1S,2R)-/(1R,2S)-erythrohydrobupropion, and (1R,2R)-/(1S,2S)-threohydrobupropion, respectively. The R-/S-bupropion and (1R,2R)-/(1S,2S)-threohydrobupropion ratios are likely indicative of higher presystemic metabolism of S- versus R-bupropion by carbonyl reductases. Interestingly, the apparent renal clearance of (2S,3S)-hydroxybupropion was almost 10-fold higher than that of (2R,3R)-hydroxybupropion. The prediction of steady-state pharmacokinetics demonstrated differential stereospecific accumulation [partial area under the plasma concentration-time curve after the final simulated bupropion dose (300-312 hours) from 185 to 37,447 nM⋅h] and elimination [terminal half-life of approximately 7-46 hours] of bupropion metabolites, which may explain observed stereoselective differences in bupropion effect and DDI risk with CYP2D6 at steady state. Further elucidation of bupropion and metabolite disposition suggests that bupropion is not a reliable in vivo marker of CYP2B6

  3. Effect of Tamarindus indica L. on the bioavailability of aspirin in healthy human volunteers.

    PubMed

    Mustapha, A; Yakasai, I A; Aguye, I A

    1996-01-01

    The influence of Tamarindus indica L. fruit extract incorporated in a traditional meal on the bioavailability of aspirin tablets 600 mg dose was studied in 6 healthy volunteers. There was a statistically significant increase in the plasma levels of aspirin and salicylic acid, respectively, when the meal containing Tamarindus indica fruit extract was administered with the aspirin tablets than when taken under fasting state or with the meal without the fruit extract. The Cmax, AUC0-6h and t1/2 for aspirin increased from 10.04 +/- 0.1 mg/ml to 28.62 +/- 0.21 mg/ml (P < 0.05); 14.03 +/- 0.11 mg/ml.h to 86.51 +/- 0.21 mg/ml.h (P < 0.085) and 1.04 +/- 0.12 h to 1.50 +/- 0.44 h (P < 0.05) respectively. There was no change in the tmax (0.50 +/- 0.17 h) but there was a decrease in the kel from 0.633 +/- 0.22 to 0.463 +/- 0.29 (P < 0.05). Similarly, the Cmax, AUC0-6h and kel for salicylic acid rose from 43.84 +/- 0.21 mg/ml to 68.19 +/- 0.71 mg/ml (P < 0.05); 171.59 +/- 0.07 mg/ml.h to 266.22 +/- 0.21 mg/ml/.h (P < 0.05) and 7.37 +/- 0.29 to 19.30 +/- 0.21 (P < 0.05), respectively. The tmax decreased from 2.0 +/- 0.18 h to 1.0 +/- 0.08 h (P < 0.05) and t1/2 from 0.25 +/- 0.21 h to 0.184 +/- 0.11 h (P < 0.05). The study has indicated that Tamarindus indica L. fruit extract significantly increased the bioavailability of aspirin.

  4. Bioequivalence study of two losartan formulations administered orally in healthy male volunteers.

    PubMed

    Bienert, Agnieszka; Brzezińiski, Rafał; Szałek, Edyta; Dubai, Vitali; Grześkowiak, Edmund; Dyderski, Stanisław; Drobnik, Leon; Wolc, Anna; Olejniczak-Rabinek, Magdalena

    2006-01-01

    The bioavailability of a new losartan preparation (2-butyl-4-chloro-1-[p-(o-1H-tetrazol-5-ylphenyl)benzyl]imidazole-5-methanol monopotassium salt, CAS 114798-26-4) was compared with the reference preparation of the drug in 24 healthy male volunteers, aged between 19 and 32. The open, randomized, single-blind two-sequence, two-period crossover study design was performed. Under fasting conditions, each subject received a single oral dose of 100 mg losartan as a test or reference formulation. The plasma concentrations of losartan and its active metabolite were analyzed by a rapid and sensitive HPLC method with UV detection. The pharmacokinetic parameters included AUC0-36h, AUC0-infinity, Cmax, t1/2, and Ke. Values of AUC0-infinity demonstrate nearly identical bioavailability of losartan from the examined formulations. The AUC0-infinity of losartan was 2019.92+/-1002.90 and 2028.58+/-837.45 ng x h/ml for the test and reference formulation, respectively. The AUC0-infinity of the metabolite was 10851.52+/-4438.66 and 11041.18 +/-5015.81 ng x h/ml for test and reference formulation, respectively. The maximum plasma concentration (Cmax) of losartan was 745.94+/-419.75 ng/ml for the test and 745.74+/-329.99 ng/ml for the reference product and the Cmax of the metabolite was 1805.77+/-765.39 and 1606.22 +/-977.22 ng/ml for the test and reference product, respectively. No statistical differences were observed for Cmax and the area under the plasma concentration-time curve for both losartan and its active metabolite. 90 % confidence limits calculated for Cmax and AUC from zero to infinity (AUC0-infinity) of losartan and its metabolite were included in the bioequivalence range (0.8-1.25 for AUC). This study shows that the test formulation is bioequivalent to the reference formulation for losartan and its main active metabolite.

  5. Diesel exhaust modulates ozone-induced lung function decrements in healthy human volunteers

    PubMed Central

    2014-01-01

    The potential effects of combinations of dilute whole diesel exhaust (DE) and ozone (O3), each a common component of ambient airborne pollutant mixtures, on lung function were examined. Healthy young human volunteers were exposed for 2 hr to pollutants while exercising (~50 L/min) intermittently on two consecutive days. Day 1 exposures were either to filtered air, DE (300 μg/m3), O3 (0.300 ppm), or the combination of both pollutants. On Day 2 all exposures were to O3 (0.300 ppm), and Day 3 served as a followup observation day. Lung function was assessed by spirometry just prior to, immediately after, and up to 4 hr post-exposure on each exposure day. Functional pulmonary responses to the pollutants were also characterized based on stratification by glutathione S-transferase mu 1 (GSTM1) genotype. On Day 1, exposure to air or DE did not change FEV1 or FVC in the subject population (n = 15). The co-exposure to O3 and DE decreased FEV1 (17.6%) to a greater extent than O3 alone (9.9%). To test for synergistic exposure effects, i.e., in a greater than additive fashion, FEV1 changes post individual O3 and DE exposures were summed together and compared to the combined DE and O3 exposure; the p value was 0.057. On Day 2, subjects who received DE exposure on Day 1 had a larger FEV1 decrement (14.7%) immediately after the O3 exposure than the individuals’ matched response following a Day 1 air exposure (10.9%). GSTM1 genotype did not affect the magnitude of lung function changes in a significant fashion. These data suggest that altered respiratory responses to the combination of O3 and DE exposure can be observed showing a greater than additive manner. In addition, O3-induced lung function decrements are greater with a prior exposure to DE compared to a prior exposure to filtered air. Based on the joint occurrence of these pollutants in the ambient environment, the potential exists for interactions in more than an additive fashion affecting lung physiological

  6. Single-dose oral guanidinoacetic acid exhibits dose-dependent pharmacokinetics in healthy volunteers.

    PubMed

    Ostojic, Sergej M; Vojvodic-Ostojic, Aleksandra

    2015-03-01

    Guanidinoacetic acid (GAA), the natural precursor of creatine, has potential as a dietary supplement for human nutrition, yet no data are available regarding its dose-dependent pharmacokinetic (PK) behavior. We hypothesized that a single dose of orally administered GAA exhibited dose-dependent PK behavior in healthy volunteers. Forty-eight young adults were enrolled in a randomized, placebo-controlled, double-blind, parallel-group trial to receive single oral doses of GAA (1.2, 2.4, and 4.8 g) or a placebo. Pharmacokinetic metrics for plasma GAA and creatine were assessed immediately before (0 hours) and at 1, 2, 4, 6, 8, 12, and 24 hours after GAA ingestion. The lag time appeared to be similar after the bolus ingestion of GAA (0.14 ± 0.17 hours for low-dose GAA, 0.31 ± 0.18 hours for medium-dose GAA, and 0.38 ± 0.32 hours for high-dose GAA; P = .05). An increase in the area under the concentration-time curve for plasma GAA was found for the dose range tested, with 2.4- and 9.3-fold increases in the area under the concentration-time curve for every 2-fold increase in the GAA dose (P < .0001). No differences were found for elimination half-time between the low-dose and medium-dose groups (<1.75 hours), whereas the elimination half-time was significantly longer (>2.1 hours) for the high-dose GAA regimen (P = .001). The volume of distribution was affected by the dosage of GAA applied (102.6 ± 17.3 L for low-dose GAA, 97.5 ± 15.7 L for medium-dose GAA, and 61.1 ± 12.7 L for high-dose GAA; P < .0001). Ingestion of GAA elevated plasma creatine by 80%, 116%, and 293% compared with the placebo for the 1.2, 2.4, and 4.8 g doses, respectively (P < .0001). Guanidinoacetic acid single-dose PK metrics were nonlinear with respect to dose size. Across the dose range of 1.2 to 4.8 g, systemic exposure to GAA increased in a greater than dose-proportional manner. PMID:25622538

  7. Bioavailability and safety study of resveratrol 500 mg tablets in healthy male and female volunteers

    PubMed Central

    SERGIDES, CHRISTAKIS; CHIRILĂ, MARINELA; SILVESTRO, LUIGI; PITTA, DAPHNE; PITTAS, ANDREAS

    2016-01-01

    Over the past few decades, trans-resveratrol has received widespread attention as a preventive agent for numerous diseases. Several studies have demonstrated that it has significant biological and pharmacological properties. Trans-resveratrol has been reported to possess anti-oxidant, anti-inflammatory, anticarcinogenic, antidiabetic, anti-aging, cardioprotective and neuroprotective properties, which can be relevant in chronic diseases and longevity in humans. The aim of the present study was to investigate the rate and extend of absorption, and also the safety of resveratrol following a single 500 mg oral dose. This was an open label, single dose, one period, bioavailability study in 15 healthy volunteers under fasting conditions. Blood samples were collected at predefined time points up to 24 h after resveratrol administration, and plasma concentrations of resveratrol and its conjugated (glucuronated and sulphated) metabolites were determined using a validated high performance liquid chromatography/tandem mass spectrometry method. Pharmacokinetic parameters, including Cmax, AUC0-t, AUC0-inf, Tmax, T1/2 and MRT, were determined from plasma concentration-time profiles and found to be in good agreement with previously reported data. Cmax and AUC0-inf were lower for resveratrol when compared with the values for its glucuronated and sulphated metabolites. Cmax for resveratrol, glucuronated resveratrol and sulphated resveratrol were 71.2±42.4 ng/ml, 4,083.9±1,704.4 ng/ml and 1,516.0±639.0 ng/ml, respectively, while the AUC0-inf values were 179.1±79.1 ng/ml, 39,732.4±16,145.6 ng/ml and 14,441.7±7,593.2 ng/ml, respectively. No adverse reactions associated with resveratrol were reported during the study. The plasma concentrations of resveratrol (free and conjugated) were in agreement with those mentioned in the literature, and were adequate to promote the pharmacological activities of resveratrol. In conclusion, resveratrol 500 mg tablets were well-tolerated by all

  8. Comparative bioavailability and pharmacokinetic study of Cefadroxil capsules in male healthy volunteers of Pakistan.

    PubMed

    Rahim, Najia; Naqvi, Syed Baqir Shyum; Alam, Mehtab; Rasheed, Abdur; Khalique, Urooj Abdul

    2016-03-01

    The current study was aimed to judge bioequivalence between two formulations of cefadroxil capsules as guided by FDA guidelines. Another objective was to conduct pharmacokinetic evaluation in Pakistani population. A single-dose, randomized, cross-over pharmacokinetic study was conducted during the month of May'2013 to August'2013. Washout period was one week. Fourteen healthy male adult volunteers were enrolled in the study, however twelve completed the study. Cefadroxil plasma concentration was analyzed by using validated HPLC method. Protein precipitation was achieved by the addition of 6% tri chloro acetic acid in 1:1 ratio and detection was done at 260 nm. Retention time was 7.792 min and correlation coefficient (R2) was 0.9953 showing linearity of the method. Blood sampling was carried out at different time intervals after administration of either test (TEST 500 mg) or reference (REF® 500 mg) formulation. Pharmacokinetic parameters (AUC0→ ∞, AUC0→ t, Cmax, Tmax, t1/2 and kel) were calculated using Kinetica® PK/PD software. The geometric mean ratios and 90% confidence interval (CI) of these pharmacokinetic parameters for cefadroxil (test and reference) formulations were 0.986 (90.83-106.98%) for AUC0→ t; 0.967 (89.13-104.92%) for AUC0→ ∞ and 0.999 (91.06-109.69%) for Cmax. The differences between Tmax of both formulations were not found to be statistically significant (p-value was more than 0.05). The 90% CI of the test/reference AUC and Cmax ratio of cefadroxil were within the FDA recommended range for bioequivalence. Maximum plasma concentration Cmax was 12.5 μg/ml for test and 12.47 μg/ml for reference formulations. Average time to reach Cmax for test and reference formulation was 1.54 and 1.5 hrs. The two formulations of cefadroxil studied during the above study were verified bioequivalent. Maximum plasma concentration of cefadroxil was lower than those mentioned in some previous studies, while Tmax and half-life were near to values reported

  9. Stopped hearts, amputated toes and NASA: contemporary legends among healthy volunteers in US phase I clinical trials

    PubMed Central

    Fisher, Jill A.

    2015-01-01

    The first stage of testing new pharmaceuticals in humans is referred to as a phase I clinical trial. The purpose of these studies is to test the safety of the drugs and to establish appropriate doses that can later be given to patients. Most of these studies are conducted under controlled, in-patient conditions using healthy volunteers who are paid for their participation. To explore healthy volunteers’ experiences in clinical trials, an ethnographic study was conducted at six in-patient phase I clinics in the USA. In addition to the observation of clinic activities (from informed consent procedures to dosing to blood draws), 268 semi-structured interviews were conducted, 33 with clinic staff and 235 with healthy volunteers. Drawing on this dataset, this article explores healthy volunteers’ exchange of contemporary legends about phase I clinical trials. In addition to potentially scaring the listener and communicating distrust in the medical community, these incredible stories help participants cope with perceived stigma and establish a gradient of risk of trial participation, creating potential boundaries to their participation in medical research. The article argues that contemporary legends play a productive role in society, shaping how people view themselves and others and influencing their decisions about risky activities. PMID:25601069

  10. Comparison of biological activities of two low molecular weight heparins in 10 healthy volunteers.

    PubMed Central

    Azizi, M; Veyssier-Belot, C; Alhenc-Gelas, M; Chatellier, G; Billaud-Mesguish, E; Fiessinger, J N; Aiach, M

    1995-01-01

    1. Low molecular weight heparins (LMWHs) are produced by different depolymerization processes and may therefore differ with respect to their pharmacokinetic properties. 2. We designed a single dose, randomized cross-over study in 10 healthy volunteers to compare the 24 h pharmacokinetics of two LMWHs, reviparin and enoxaparin, which have been previously shown to be clinically equivalent in terms of post-operative deep vein thrombosis prevention, despite significant differences in their in vivo biological activity. The two LMWHs were subcutaneously administered at the same dosages that are used in clinical studies: 4250 anti-Xa iu for reviparin and 40 mg for enoxaparin which have similar in vitro anti-Xa activities. 3. The overall 24 h profiles of the plasma anti-Xa and anti-thrombin activities were similar for reviparin and enoxaparin. The Amax and the AUC(0, 24h) of plasma anti-Xa activity after reviparin administration were both slightly but significantly lower than those observed after enoxaparin administration (difference between treatments of 0.03 95% CI[0.01-0.05] iu ml-1 h and 0.56 95% CI[0.22-0.90] iu ml-1 for Amax and AUC(0, 24h) respectively). After adjustment for in vitro anti-Xa activity, the statistical difference between the two LMWHs persisted for the AUC(0, 24h) but not for the Amax of plasma anti-Xa activity. The tmax and the MRT values for plasma anti-Xa activity did not significantly differ between the two drugs. The t1/2 for reviparin did not significantly differ from that of enoxaparin (2.7 +/- 0.7 h vs 3.5 +/- 0.9 h respectively, NS). The Amax of the plasma anti-thrombin activity after reviparin administration was also slightly but significantly lower than that observed after enoxaparin administration, (difference between treatments of 0.018 95% CI[0.01-0.025] iu ml-1) whereas the AUC(0, 24h) of anti-thrombin activity vs time was not. A slight but significant increase of the activated partial thromboplastin time of a similar magnitude was

  11. Effectiveness of Topical Chia Seed Oil on Pruritus of End-stage Renal Disease (ESRD) Patients and Healthy Volunteers

    PubMed Central

    Jeong, Se Kyoo; Park, Hyun Jung; Park, Byeong Deog

    2010-01-01

    Background Several studies have been performed to evaluate the efficacy of dietary n-3 fatty acid for patients with renal dysfunction. While about 40% to 80% of patients with end-stage renal disease (ESRD) complain about pruritus and xerosis, there are few reports on the effects of topical n-3 fatty acid on these symptoms. Objective In order to investigate the possible beneficial effects of topical n-3 fatty acid, oils extracted from chia (Salvia hispanica) seed were formulated into topical products, the effects of which were measured. Methods Five healthy volunteers having xerotic pruritus symptoms and 5 patients with pruritus caused by either ESRD or diabetes were involved in this study. A topical formulation containing 4% chia seed oils were applied for an 8-week duration. Subjective itching symptoms were assessed on a 6-point scale, as were other skin functions, namely transepidermal water loss and skin capacitance. Results After the 8 weeks of application, significant improvements in skin hydration, lichen simplex chronicus, and prurigo nodularis were observed in all patients. A similar improvement was also observed among healthy volunteers with xerotic pruritus. Improvement of epidermal permeability barrier function and skin hydration, represented by trans-epidermal water loss and skin capacitance, respectively, were also observed. No adverse effects were observed in all the tested patients and volunteers. Conclusion Chia seed oil can be used as an adjuvant moisturizing agent for pruritic skin, including that of ESRD patients. PMID:20548903

  12. The use of a scopolamine model to study the potential nootropic effects of aniracetam and piracetam in healthy volunteers.

    PubMed

    Wesnes, K; Anand, R; Simpson, P; Christmas, L

    1990-01-01

    In this study 26 healthy volunteers received scopolamine 0.7 mg subcutaneously on seven occasions at least a week apart. Cognitive efficiency was measured with a test battery before and 60 min following scopolamine on each occasion. Following this, over the seven occasions, a range of oral and intravenous dose regimens were administered including aniracetam 2 mg intravenously, 100 mg intravenously, 200 mg intravenously, 1500 mg per os and piracetam 2400 mg per os. On each session the test battery was then performed again at 120 and 200 min following scopolamine. The seven treatments were administered double- blind and the order was counterbalanced between volunteers over visits using a Latin Square design. At 60 min, scopolamine produced marked and significant decrements in all of the measures of memory and information processing. Aniracetam 1500 mg was able to sig nificantly antagonize decrements on both memory and information processing tasks. The other active treatments also produced significant effects, but for two these were equal to, and for two slightly above, the number which may have occurred by chance, and thus were questionable. Overall, the findings demonstrate that aniracetam 1500 mg can antagonize cognitive decrements produced by cholinergic blockade in healthy volunteers, and suggest that the drug possesses nootropic properties.

  13. The Vaccine Candidate Vibrio cholerae 638 Is Protective against Cholera in Healthy Volunteers

    PubMed Central

    García, Luis; Jidy, Manuel Díaz; García, Hilda; Rodríguez, Boris L.; Fernández, Roberto; Año, Gemma; Cedré, Bárbara; Valmaseda, Tania; Suzarte, Edith; Ramírez, Margarita; Pino, Yadira; Campos, Javier; Menéndez, Jorge; Valera, Rodrigo; González, Daniel; González, Irma; Pérez, Oliver; Serrano, Teresita; Lastre, Miriam; Miralles, Fernando; del Campo, Judith; Maestre, Jorge Luis; Pérez, José Luis; Talavera, Arturo; Pérez, Antonio; Marrero, Karen; Ledón, Talena; Fando, Rafael

    2005-01-01

    Vibrio cholerae 638 is a living candidate cholera vaccine strain attenuated by deletion of the CTXΦ prophage from C7258 (O1, El Tor Ogawa) and by insertion of the Clostridium thermocellum endoglucanase A gene into the hemagglutinin/protease coding sequence. This vaccine candidate was previously found to be well tolerated and immunogenic in volunteers. This article reports a randomized, double-blind, placebo-controlled trial conducted to test short-term protection conferred by 638 against subsequent V. cholerae infection and disease in volunteers in Cuba. A total of 45 subjects were enrolled and assigned to receive vaccine or placebo. The vaccine contained 109 CFU of freshly harvested 638 buffered with 1.3% NaHCO3, while the placebo was buffer alone. After vaccine but not after placebo intake, 96% of volunteers had at least a fourfold increase in vibriocidal antibody titers, and 50% showed a doubling of at least the lipopolysaccharide-specific immunoglobulin A titers in serum. At 1 month after vaccination, five volunteers from the vaccine group and five from the placebo group underwent an exploratory challenge study with 109 CFU of ΔCTXΦ attenuated mutant strain V. cholerae 81. Only two volunteers from the vaccine group shed strain 81 in their feces, but none of them experienced diarrhea; in the placebo group, all volunteers excreted the challenge strain, and three had reactogenic diarrhea. An additional 12 vaccinees and 9 placebo recipients underwent challenge with 7 × 105 CFU of virulent strain V. cholerae 3008 freshly harvested from a brain heart infusion agar plate and buffered with 1.3% NaHCO3. Three volunteers (25%) from the vaccine group and all from the placebo group shed the challenge agent in their feces. None of the 12 vaccinees but 7 volunteers from the placebo group had diarrhea, and 2 of the latter exhibited severe cholera (>5,000 g of diarrheal stool). These results indicate that at 1 month after ingestion of a single oral dose (109 CFU) of strain

  14. Validating the inhalation of 7.5% CO(2) in healthy volunteers as a human experimental medicine: a model of generalized anxiety disorder (GAD).

    PubMed

    Bailey, Jayne E; Dawson, Gerard R; Dourish, Colin T; Nutt, David J

    2011-09-01

    Anxiety is a complex phenomenon that can represent contextually different experiences to individuals. The experimental modelling in healthy volunteers of clinical anxiety experienced by patients is challenging. Furthermore, defining when and why anxiety (which is adaptive) becomes an anxiety disorder (and hence maladaptive) is the subject of much of the published literature. Observations from animal studies can be helpful in deriving mechanistic models, but gathering evidence from patients and reverse translating this to healthy volunteers and thence back to laboratory models is a more powerful approach and is likely to more closely model the clinical disorder. Thus the development and validation of a robust healthy volunteer model of anxiety may help to bridge the gap between the laboratory and the clinic and provide 'proof of concept' in screening for novel drug treatments. This review considers these concepts and outlines evidence from a validated healthy volunteer model of generalized anxiety disorder (GAD) following the inhalation of 7.5% CO(2).

  15. Defining Normal Liver Stiffness Range in a Normal Healthy Chinese Population without Liver Disease

    PubMed Central

    Fung, James; Lee, Cheuk-kwong; Chan, Monica; Seto, Wai-kay; Wong, Danny Ka-ho; Lai, Ching-lung; Yuen, Man-fung

    2013-01-01

    Background For patients with chronic liver disease, different optimal liver stiffness cut-off values correspond to different stages of fibrosis, which are specific for the underlying liver disease and population. Aims To establish the normal ranges of liver stiffness in the healthy Chinese population without underlying liver disease. Methods This is a prospective cross sectional study of 2,528 healthy volunteers recruited from the general population and the Red Cross Transfusion Center in Hong Kong. All participants underwent a comprehensive questionnaire survey, measurement of weight, height, and blood pressure. Fasting liver function tests, glucose and cholesterol was performed. Abdominal ultrasound and transient elastography were performed on all participants. Results Of the 2,528 subjects, 1,998 were excluded with either abnormal liver parenchyma on ultrasound, chronic medical condition, abnormal blood tests including liver enzymes, fasting glucose, fasting cholesterol, high body mass index, high blood pressure, or invalid liver stiffness scan. The reference range for the 530 subjects without known liver disease was 2.3 to 5.9 kPa (mean 4.1, SD 0.89). The median liver stiffness was higher in males compared with females (4.3 vs 4.0 kPa respectively, p<0.001). There was also a decline in median Lliver stiffness in the older age group, from 4.2 kPa in those <25 years to 3.4 kPa for those >55 years (p=0.001). Conclusions The healthy reference range for liver stiffness in the Chinese population is 2.3 to 5.9 kPa. Female gender and older age group was associated with a lower median liver stiffness. PMID:24386446

  16. A validation of the 7.5% CO2 model of GAD using paroxetine and lorazepam in healthy volunteers.

    PubMed

    Bailey, Jayne E; Kendrick, Adrian; Diaper, Alison; Potokar, John P; Nutt, David J

    2007-01-01

    The inhalation of 7.5% carbon dioxide (CO2) in healthy subjects produces an increase in blood pressure and heart rate, and increased feelings of anxiety, fear and tension (Bailey et al. 2005). As this state is similar to that of general anxiety rather than panic, we further validated this by examining the effects of anxiolytic medication. Two separate studies in healthy volunteers are described; study one is a double-blind, placebo-controlled study of a single dose of 2 mg lorazepam and study two describes the effects of 21 days of treatment with paroxetine. Gas challenges were air and 7.5% CO2 inhaled for 20 minutes, delivered on day 0 (before treatment) and day 21 (after treatment) in the paroxetine study. Subjective effects were measured using visual analogue scales and questionnaires. When compared with placebo, lorazepam 2 mg significantly reduced peak CO2-induced subjective fear, feelings of wanting to leave, tension and worry. In the paroxetine study, when compared with day 0, day 21 showed a significantly attenuated peak CO2-induced nervousness and a trend for reduced ratings of anxiety, fear, feel like leaving, tense and worried. In these studies we have shown that this CO2 model of anxiety is sensitive to lorazepam and to a lesser extent paroxetine. This gives support to its utility as an experimental model of general anxiety disorder in healthy volunteers. PMID:16533865

  17. Trace elements in fingernails of healthy Chinese centenarians.

    PubMed

    Li, Yonghua; Zou, Xiaoyan; Lv, Jinmei; Yang, Linsheng; Li, Hairong; Wang, Wuyi

    2012-02-01

    Trace element concentrations in body tissues of healthy centenarians have not been widely analyzed, yet they can be used as reference data leading to improved assessment of the aging process and monitoring of the micronutrient status of this age group. The present study sought to assess trace element concentrations and behaviors in the fingernails of healthy Chinese centenarians. The effects of gender on element concentrations, which also play an important role in determining the lifespan, were also investigated. Trace elements (Ba, Cd, Co, Cr, Cu, Fe, Li, Mn, Mo, Ni, Pb, Se, Sr, and Zn) in the fingernails of 78 healthy Chinese centenarians were determined by inductively coupled plasma mass spectrometry. The overall reference values obtained in milligram per kilogram are as follows: Ba, 5.10; Cd, 0.031; Co, 0.101; Cr, 0.82; Cu, 3.71; Fe, 154.35; Li, 0.31; Mn, 3.09; Mo, 0.040; Ni, 0.95; Pb, 1.86; Se, 0.44; Sr, 6.20; and Zn, 147.96. Data analysis showed that only Cr and Se concentrations show a normal distribution, and no significant difference between male and female groups was found for any element except Cr. Result also revealed that sufficient Se, Co, and Zn as well as lower or lack of exposure to Cr contribute positively to the lifespan of centenarians. The results suggest that regulating in vivo contents of trace elements, especially Se, Co, and Zn, is reasonable to intervene with geriatric diseases.

  18. Peak oxygen uptake in relation to total heart volume discriminates heart failure patients from healthy volunteers and athletes

    PubMed Central

    2010-01-01

    Background An early sign of heart failure (HF) is a decreased cardiac reserve or inability to adequately increase cardiac output during exercise. Under normal circumstances maximal cardiac output is closely related to peak oxygen uptake (VO2peak) which has previously been shown to be closely related to total heart volume (THV). Thus, the aim of this study was to derive a VO2peak/THV ratio and to test the hypothesis that this ratio can be used to distinguish patients with HF from healthy volunteers and endurance athletes. Thirty-one patients with HF of different etiologies were retrospectively included and 131 control subjects (60 healthy volunteers and 71 athletes) were prospectively enrolled. Peak oxygen uptake was determined by maximal exercise test and THV was determined by cardiovascular magnetic resonance. The VO2peak/THV ratio was then derived and tested. Results Peak oxygen uptake was strongly correlated to THV (r2 = 0.74, p < 0.001) in the control subjects, but not for the patients (r2 = 0.0002, p = 0.95). The VO2peak/THV ratio differed significantly between control subjects and patients, even in patients with normal ejection fraction and after normalizing for hemoglobin levels (p < 0.001). In a multivariate analysis the VO2peak/THV ratio was the only independent predictor of presence of HF (p < 0.001). Conclusions The VO2peak/THV ratio can be used to distinguish patients with clinically diagnosed HF from healthy volunteers and athletes, even in patients with preserved systolic left ventricular function and after normalizing for hemoglobin levels. PMID:21162743

  19. Imaging and Quantification of Subbasal Nerve Plexus in Healthy Volunteers and Diabetic Patients with or without Retinopathy

    PubMed Central

    Hovakimyan, Marine; Peschel, Sabine; Harder, Volker; Schober, Hans-Christof; Kundt, Guenther; Baltrusch, Simone; Guthoff, Rudolf F.; Stachs, Oliver

    2013-01-01

    Background The alterations of subbasal nerve plexus (SBP) innervation and corneal sensation were estimated non-invasively and compared with the values in healthy volunteers. Additionally, this study addressed the relation of SBP changes to the retinal status, glycemic control and diabetes duration. Methodology/Principal Findings Eighteen eyes of diabetic patients with peripheral diabetic neuropathy aged 68.8±8.8 years and twenty eyes of healthy volunteers aged 66.3±13.3 yrs. were investigated with in vivo confocal laser-scanning microscopy (CLSM). An adapted algorithm for image analysis was used to quantify the morphological and topological properties of SBP. These properties were correlated to incidence of diabetic retinopathy (DR) and corneal sensation (Cochet-Bonnet esthesiometer). The developed algorithm allows a fully automated analysis of pre-segmented SBP structures. Altogether, 10 parameters were analysed, and all of them revealed significant differences between diabetic patients and healthy volunteers. The nerve fibre density, total fibre length and nerve branches were found to be significantly lower in patients with diabetes than those of control subjects (nerve fibre density 0.006±0.002 vs. 0.020±0.007 mm/mm2; total fibre length 6223±2419 vs. 19961±6553 µm; nerve branches 25.3±28.6 vs. 141.9±85.7 in healthy volunteers). Also the corneal sensation was significantly lower in diabetic group when compared to controls (43±11 vs. 59±18 mm). There was found no difference in SBP morphology or corneal sensation in the subgroups with (DR) or without (NDR) diabetic retinopathy. Conclusions/Significance SBP parameters were significantly reduced in diabetic patients, compared to control group. Interestingly, the SBP impairment could be shown even in the diabetic patients without DR. Although automatic adapted image analysis simplifies the evaluation of in vivo CLSM data, image acquisition and quantitative analysis should be optimised for the everyday

  20. Comparison of Oseltamivir and Oseltamivir Carboxylate Concentrations in Venous Plasma, Venous Blood, and Capillary Blood in Healthy Volunteers

    PubMed Central

    Instiaty, Insti; Lindegardh, Niklas; Jittmala, Podjanee; Hanpithakpong, Warunee; Blessborn, Daniel; Pukrittayakamee, Sasithon; White, Nicholas J.

    2013-01-01

    Oseltamivir and oseltamivir carboxylate concentrations were measured in venous plasma, venous blood, and capillary blood taken simultaneously from 24 healthy volunteers. Median (range) venous-blood-to-plasma ratios were 1.42 (0.920 to 1.97) for oseltamivir and 0.673 (0.564 to 0.814) for oseltamivir carboxylate. Capillary blood/venous plasma ratios were 1.32 (0.737 to 3.16) for oseltamivir and 0.685 (0.502 to 1.34) for oseltamivir carboxylate. Oseltamivir concentrations in venous and capillary blood were similar. Oseltamivir carboxylate showed a time-dependent distribution between venous and capillary blood. PMID:23507284

  1. Scarce evidence of yogurt lactic acid bacteria in human feces after daily yogurt consumption by healthy volunteers.

    PubMed

    del Campo, Rosa; Bravo, Daniel; Cantón, Rafael; Ruiz-Garbajosa, Patricia; García-Albiach, Raimundo; Montesi-Libois, Alejandra; Yuste, Francisco-Javier; Abraira, Victor; Baquero, Fernando

    2005-01-01

    In a double-blind prospective study including 114 healthy young volunteers, the presence in human feces of the yogurt organisms Lactobacillus delbrueckii and Streptococcus thermophilus after repeated yogurt consumption (15 days) was analyzed by culture, specific PCR, and DNA hybridization of total fecal DNA. Detection of yogurt lactic acid bacteria in total fecal DNA by bacterial culture and PCR assay was consistently negative. DNA compatible with yogurt bacteria was found by hybridization experiments in only 10 (10.52%) of 96 individuals after consumption of fresh yogurt and in 2 (2.10%) of 96 individuals after consumption of pasteurized yogurt (P = 0.01).

  2. Trace element concentrations in hair of healthy Chinese centenarians.

    PubMed

    Li, Yonghua; Yang, Linsheng; Wang, Wuyi; Li, Hairong; Lv, Jinmei; Zou, Xiaoyan

    2011-03-15

    Trace element concentrations, as indicators of micronutrient status of healthy centenarians, have not been widely analyzed. This study aimed to assess trace element concentrations in the hair of healthy centenarians. The effects of gender and age on element concentrations were also investigated. Eleven trace elements (Al, Ba, Cd, Cr, Cu, Fe, Mo, Pb, Se, Sr and Zn) in the scalp hair of 107 healthy Chinese centenarians were examined. The overall reference values (RVs) in mg/kg for the hair concentrations of trace elements in centenarians were as follows: Al, 14.95; Ba, 2.68; Cd, 0.06; Cr, 0.59; Cu, 6.21); Fe, 19.37; Mo, 0.50; Pb, 4.64; Se, 0.37; Sr, 4.84; and Zn, 154.37. Data analysis found that only Cu and Zn concentrations show a normal distribution, and there is no significant difference between males and females in any element except Zn. However, the levels of Al, Cd, Cr, Fe, Mo, Pb decrease and the levels of Ba, Cu, Se, Sr, Zn increase with age in the centenarian cohort. Results also revealed that sufficient Zn and Se concentrations as well as low exposure to heavy metals pollution contribute to the longevity of centenarians. The results imply the possibility of manipulating trace element concentrations, especially Zn and Se concentrations in tissues, as a means for therapeutic modality in geriatric disease.

  3. Randomized, Double-Blind Clinical Trial to Assess the Acute Diuretic Effect of Equisetum arvense (Field Horsetail) in Healthy Volunteers

    PubMed Central

    Carneiro, Danilo Maciel; Freire, Ramias Calixto; Honório, Tereza Cristina de Deus; Zoghaib, Iury; Cardoso, Fabiana Fernandes de S. e Silva; Tresvenzol, Leonice Manrique F.; de Paula, José Realino; Sousa, Ana Luiza Lima; Jardim, Paulo César Brandão Veiga; da Cunha, Luiz Carlos

    2014-01-01

    In this double-blind, randomized clinical trial, 36 healthy male volunteers were randomly distributed into three groups (n = 12) that underwent a three-step treatment. For four consecutive days, we alternately administered a standardized dried extract of Equisetum arvense (EADE, 900 mg/day), placebo (corn starch, 900 mg/day), or hydrochlorothiazide (25 mg/day), separated by a 10-day washout period. Each volunteer served as his own control, and the groups' results were compared. We repeated the same evaluation after each stage of treatment to evaluate the safety of the drug. The diuretic effect of EADE was assessed by monitoring the volunteers' water balance over a 24 h period. The E. arvense extract produced a diuretic effect that was stronger than that of the negative control and was equivalent to that of hydrochlorothiazide without causing significant changes in the elimination of electrolytes. There was no significant increase in the urinary elimination of catabolites. Rare minor adverse events were reported. The clinical examinations and laboratory tests showed no changes before or after the experiment, suggesting that the drug is safe for acute use. Further research is needed to better clarify the mechanism of diuretic action and the other possible pharmacological actions of this phytomedicine. PMID:24723963

  4. The effect of CYP3A inhibitors and inducers on the pharmacokinetics of telaprevir in healthy volunteers

    PubMed Central

    Garg, Varun; Chandorkar, Gurudatt; Yang, Yijun; Adda, Nathalie; McNair, Lindsay; Alves, Katia; Smith, Frances; Heeswijk, Rolf P G

    2013-01-01

    AIM To evaluate the effects of ketoconazole, rifampicin and efavirenz on the pharmacokinetics of telaprevir in healthy volunteers. METHOD Results from three clinical studies are described. (1) Volunteers received a single 750 mg dose telaprevir with and without a single 400 mg dose ketoconazole. (2) Volunteers received (a) 1250 mg telaprevir followed by three 750 mg doses given every 8 h and (b) four 1250 mg telaprevir doses given every 8 h, with a single 400 mg dose ketoconazole given with the fourth dose of telaprevir. (3) Volunteers received either a single 750 mg dose telaprevir with or without 600 mg once daily rifampicin, or 750 mg every 8 h telaprevir with and without 600 mg once daily efavirenz. RESULTS A single 400 mg dose of ketoconazole increased single dose telaprevir exposure: the geometric least-squares mean ratio (GLSMR, with 90% confidence limits) was 1.24 (1.10, 1.41) for Cmax and 1.62 (1.45, 1.81) for AUC(0,∞). However, after multiple doses of telaprevir, there was no discernible effect of ketoconazole on telaprevir exposure. Co-administration of rifampicin at steady-state markedly reduced single dose telaprevir exposure with GLSMRs of 0.14 (0.11, 0.18) for Cmax and 0.08 (0.07, 0.11) for AUC(0,∞), whereas efavirenz had a smaller effect on telaprevir exposure when both drugs were co-administered at steady-state, with GLSMRs of 0.91 (0.81, 1.02) for Cmax, 0.53 (0.44, 0.65) for Cmin, and 0.74 (0.65, 0.84) for AUC(0,8 h). CONCLUSION CYP3A inducers, rifampicin and efavirenz, can reduce telaprevir exposure to varying degrees based on their potency. The effect of ketoconazole as an inhibitor of telaprevir metabolism is more pronounced after a single dose of telaprevir than after repeated administration. PMID:22642697

  5. The γ-Secretase Modulator, BMS-932481, Modulates Aβ Peptides in the Plasma and Cerebrospinal Fluid of Healthy Volunteers.

    PubMed

    Soares, Holly D; Gasior, Maciej; Toyn, Jeremy H; Wang, Jun-Sheng; Hong, Quan; Berisha, Flora; Furlong, Michael T; Raybon, Joseph; Lentz, Kimberley A; Sweeney, Francis; Zheng, Naiyu; Akinsanya, Billy; Berman, Robert M; Thompson, Lorin A; Olson, Richard E; Morrison, John; Drexler, Dieter M; Macor, John E; Albright, Charlie F; Ahlijanian, Michael K; AbuTarif, Malaz

    2016-07-01

    The pharmacokinetics, pharmacodynamics, safety, and tolerability of BMS-932481, a γ-secretase modulator (GSM), were tested in healthy young and elderly volunteers after single and multiple doses. BMS-932481 was orally absorbed, showed dose proportionality after a single dose administration, and had approximately 3-fold accumulation after multiple dosing. High-fat/caloric meals doubled the Cmax and area under the curve and prolonged Tmax by 1.5 hours. Consistent with the preclinical pharmacology of GSMs, BMS-932481 decreased cerebrospinal fluid (CSF) Aβ39, Aβ40, and Aβ42 while increasing Aβ37 and Aβ38, thereby providing evidence of γ-secretase enzyme modulation rather than inhibition. In plasma, reductions in Aβ40 and Aβ42 were observed with no change in total Aβ; in CSF, modest decreases in total Aβ were observed at higher dose levels. Increases in liver enzymes were observed at exposures associated with greater than 70% CSF Aβ42 lowering after multiple dosing. Although further development was halted due to an insufficient safety margin to test the hypothesis for efficacy of Aβ lowering in Alzheimer's disease, this study demonstrates that γ-secretase modulation is achievable in healthy human volunteers and supports further efforts to discover well tolerated GSMs for testing in Alzheimer's disease and other indications. PMID:27189973

  6. The γ-Secretase Modulator, BMS-932481, Modulates Aβ Peptides in the Plasma and Cerebrospinal Fluid of Healthy Volunteers

    PubMed Central

    Gasior, Maciej; Toyn, Jeremy H.; Wang, Jun-Sheng; Hong, Quan; Berisha, Flora; Furlong, Michael T.; Raybon, Joseph; Lentz, Kimberley A.; Sweeney, Francis; Zheng, Naiyu; Akinsanya, Billy; Berman, Robert M.; Thompson, Lorin A.; Olson, Richard E.; Morrison, John; Drexler, Dieter M.; Macor, John E.; Albright, Charlie F.; Ahlijanian, Michael K.; AbuTarif, Malaz

    2016-01-01

    The pharmacokinetics, pharmacodynamics, safety, and tolerability of BMS-932481, a γ-secretase modulator (GSM), were tested in healthy young and elderly volunteers after single and multiple doses. BMS-932481 was orally absorbed, showed dose proportionality after a single dose administration, and had approximately 3-fold accumulation after multiple dosing. High-fat/caloric meals doubled the Cmax and area under the curve and prolonged Tmax by 1.5 hours. Consistent with the preclinical pharmacology of GSMs, BMS-932481 decreased cerebrospinal fluid (CSF) Aβ39, Aβ40, and Aβ42 while increasing Aβ37 and Aβ38, thereby providing evidence of γ-secretase enzyme modulation rather than inhibition. In plasma, reductions in Aβ40 and Aβ42 were observed with no change in total Aβ; in CSF, modest decreases in total Aβ were observed at higher dose levels. Increases in liver enzymes were observed at exposures associated with greater than 70% CSF Aβ42 lowering after multiple dosing. Although further development was halted due to an insufficient safety margin to test the hypothesis for efficacy of Aβ lowering in Alzheimer’s disease, this study demonstrates that γ-secretase modulation is achievable in healthy human volunteers and supports further efforts to discover well tolerated GSMs for testing in Alzheimer’s disease and other indications. PMID:27189973

  7. Sensitive and specific radioimmunoassay for fialuridine: initial assessment of pharmacokinetics after single oral doses to healthy volunteers.

    PubMed Central

    Bowsher, R R; Compton, J A; Kirkwood, J A; Place, G D; Jones, C D; Mabry, T E; Hyslop, D L; Hatcher, B L; DeSante, K A

    1994-01-01

    Fialuridine (FIAU) is a halogen-substituted analog of thymidine that was undergoing clinical investigation as a drug for the treatment of chronic hepatitis B viral infection. However, clinical trials of FIAU were terminated after adverse events occurred following chronic oral administration. Prior to the termination of clinical trials, a sensitive assay was needed for the measurement of FIAU because of the anticipated low dose administered to patients. We therefore undertook the development of a radioimmunoassay (RIA). A specific antiserum was raised in rabbits following immunization with a 5'-O-hemisuccinate analog of FIAU coupled to keyhole limpet hemocyanin. Radiolabeled FIAU was synthesized by a destannylation procedure by using sodium [125I]iodide. We developed a competitive-binding procedure and used precipitation with polyethylene glycol as the method for separating the bound and free forms of FIAU. The RIA is sensitive (0.2 ng/ml), specific (negligible interference from known metabolites and endogenous nucleosides), and reproducible (interassay coefficients of variation range from 5 to 19.7% for serum controls). We used the RIA to assess the pharmacokinetics of FIAU in healthy adult volunteers following administration of a single 5-mg oral dose. The sensitivity of the RIA permitted the detection of a prolonged elimination phase for FIAU in healthy volunteers and dogs, with mean elimination half-lives of 29.3 and 35.3 h, respectively. We conclude the RIA is a valid method for the quantification of FIAU in biological fluids. PMID:7811032

  8. A food effect study and dose proportionality study to assess the pharmacokinetics and safety of bardoxolone methyl in healthy volunteers.

    PubMed

    Teuscher, Nathan S; Kelley, Richard J; Dumas, Emily O; Klein, Cheri Enders; Awni, Walid M; Meyer, Colin J

    2014-07-01

    This study investigated the effect of food on the plasma pharmacokinetics of bardoxolone methyl, an antioxidant inflammation modulator, at a 20 mg dose, and the dose proportionality of bardoxolone methyl pharmacokinetics from 20 to 80 mg. It was a single-dose study conducted at a single center in 32 healthy volunteers aged 18-45 years using an amorphous spray-dried dispersion formulation of bardoxolone methyl. In Part A, 16 subjects received single 20 mg doses of bardoxolone methyl under fasting and non-fasting conditions. In Part B, 16 subjects received a single 60 or 80 mg dose of bardoxolone methyl and a matching placebo dose under fasting conditions. Blood samples for pharmacokinetic analysis were taken over 120 hours following dose administration. Single dose administration of 20, 60, and 80 mg bardoxolone methyl was safe and well-tolerated in healthy volunteers. Total bardoxolone methyl exposure was unchanged in the presence of food. However, doses of bardoxolone methyl above 20 mg appear to have a saturated dissolution or absorption process and are associated with less than proportional increases in drug exposure. PMID:27128838

  9. Sphenopalatine Ganglion Acupuncture Improves Nasal Ventilation and Modulates Autonomic Nervous Activity in Healthy Volunteers: A Randomized Controlled Study

    PubMed Central

    Wang, Kuiji; Chen, Luquan; Wang, Yang; Wang, Chengshuo; Zhang, Luo

    2016-01-01

    The study aimed to assess the effects of Sphenopalatine ganglion (SPG) acupuncture on nasal ventilation function and autonomic nervous system in health volunteers. 39 healthy subjects were randomly assigned to either active SPG acupuncture group (AA group) or sham-SPG acupuncture group (SA group). All subjects were assessed for self-reported nasal ventilation, nasal patency (nasal airway resistance (NAR) and nasal cavity volume (NCV), exhaled nasal nitric oxide (nNO), and neuropeptides (substance P(SP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY)) in nasal secretions at baseline, 30 minutes, 2 hours, and 24 hours after acupuncture. Significantly more subjects in AA group reported improvements in nasal ventilation at all time points after acupuncture, compared to SA group. NAR and NCV were also significantly lower in AA group than SA group. The level of nNO in AA group was significantly decreased after 24 hours compared to SA group. The level of NPY was significantly increased in AA group at 30 minutes and 2 hours compared to baseline and SA group. The levels of SP and VIP were not significantly different in the two groups. We concluded that SPG acupuncture could help to improve nasal ventilation by increasing sympathetic nerve excitability in healthy volunteers. PMID:27425415

  10. Relative indexes of cutaneous blood perfusion measured by real-time laser Doppler imaging (LDI) in healthy volunteers.

    PubMed

    Seyed Jafari, S Morteza; Schawkat, Megir; Van De Ville, Dimitri; Shafighi, Maziar

    2014-07-01

    We used real-time LDI to study regional variations in microcirculatory perfusion in healthy candidates to establish a new methodology for global perfusion body mapping that is based on intra-individual perfusion index ratios. Our study included 74 (37 female) healthy volunteers aged between 22 and 30 years (mean 24.49). Imaging was performed using a recent microcirculation-imaging camera (EasyLDI) for different body regions of each volunteer. The perfusion values were reported in Arbitrary Perfusion Units (APU). The relative perfusion indexes for each candidate's body region were then obtained by normalization with the perfusion value of the forehead. Basic parameters such as weight, height, and blood pressure were also measured and analyzed. The highest mean perfusion value was reported in the forehead area (259.21APU). Mean perfusion in the measured parts of the body correlated positively with mean forehead value, while there was no significant correlation between forehead blood perfusion values and room temperature, BMI, systolic blood pressure and diastolic blood pressure (p=0.420, 0.623, 0.488, 0.099, respectively). Analysis of the data showed that perfusion indexes were not significantly different between male and female volunteers except for the ventral upper arm area (p=.001). LDI is a non-invasive, fast technique that opens several avenues for clinical applications. The mean perfusion indexes are useful in clinical practice for monitoring patients before and after surgical interventions. Perfusion values can be predicted for different body parts for patients only by taking the forehead perfusion value and using the perfusion index ratios to obtain expected normative perfusion values. PMID:24788075

  11. Relative indexes of cutaneous blood perfusion measured by real-time laser Doppler imaging (LDI) in healthy volunteers.

    PubMed

    Seyed Jafari, S Morteza; Schawkat, Megir; Van De Ville, Dimitri; Shafighi, Maziar

    2014-07-01

    We used real-time LDI to study regional variations in microcirculatory perfusion in healthy candidates to establish a new methodology for global perfusion body mapping that is based on intra-individual perfusion index ratios. Our study included 74 (37 female) healthy volunteers aged between 22 and 30 years (mean 24.49). Imaging was performed using a recent microcirculation-imaging camera (EasyLDI) for different body regions of each volunteer. The perfusion values were reported in Arbitrary Perfusion Units (APU). The relative perfusion indexes for each candidate's body region were then obtained by normalization with the perfusion value of the forehead. Basic parameters such as weight, height, and blood pressure were also measured and analyzed. The highest mean perfusion value was reported in the forehead area (259.21APU). Mean perfusion in the measured parts of the body correlated positively with mean forehead value, while there was no significant correlation between forehead blood perfusion values and room temperature, BMI, systolic blood pressure and diastolic blood pressure (p=0.420, 0.623, 0.488, 0.099, respectively). Analysis of the data showed that perfusion indexes were not significantly different between male and female volunteers except for the ventral upper arm area (p=.001). LDI is a non-invasive, fast technique that opens several avenues for clinical applications. The mean perfusion indexes are useful in clinical practice for monitoring patients before and after surgical interventions. Perfusion values can be predicted for different body parts for patients only by taking the forehead perfusion value and using the perfusion index ratios to obtain expected normative perfusion values.

  12. Effects of quercetin on pharmacokinetics of cefprozil in Chinese-Han male volunteers.

    PubMed

    Jia, Fei-Fei; Tan, Zhi-Rong; McLeod, Howard L; Chen, Yao; Ou-Yang, Dong-Sheng; Zhou, Hong-Hao

    2016-10-01

    1. The primary objective of this study was to evaluate the effects of quercetin on the pharmacokinetics of cefprozil. The secondary objective was to evaluate the safety of the combined use of cefprozil and quercetin. 2. An open-label, two-period, crossover phase I trial among 24 Han Chinese male subjects was conducted. Participants were given 500 mg of quercetin orally once daily for 15 d followed by single dose of cefprozil (500 mg) on day 15. Serum concentrations of cefprozil were then measured in all participants on day 15. A 15-d washout period was then assigned after which a 500 mg dose of cefprozil was administered and measured in the serum on day 36. 3. All subjects completed the trial, and no serious adverse events were reported. We measured mean serum concentrations of cefprozil in the presence and absence of quercetin in all participants. The maximum serum concentration of cefprozil in the presence of quercetin was 8.18 ug/ml (95% CI: 7.55-8.81) versus a maximum cefprozil concentration of 8.35 ug/ml (95% CI: 7.51-9.19) in the absence of quercetin. We conclude that the concurrent use of quercetin has no substantial effect on serum concentrations of orally administered cefprozil. 4. Co-administration of quercetin showed no statistically significant effects on the pharmacokinetics of cefprozil in healthy Chinese subjects.

  13. Metabolic effects of atenolol and doxazosin in healthy volunteers during prolonged physical exercise.

    PubMed

    Cosenzi, A; Sacerdote, A; Bocin, E; Molino, R; Mangiarotti, M; Bellini, G

    1995-01-01

    Nonselective beta-blockers may reduce exercise performance, not only through hemodynamic but also through metabolic effects. During prolonged physical exertion, lipolysis induced by plasma epinephrine occurs through beta-adrenoceptors of adipocytes. Therefore, beta-blockade may reduce release of free fatty acids (FFA) from adipocytes and consequently the energy supply for muscle cells. In this single-blind study, we compared the metabolic effects of atenolol with those of doxazosin, an alpha 1-blocker, during exercise in 26 young volunteers (age 20-35 years). All subjects performed an exercise test on a bicycle ergometer 5 h after consuming a standard breakfast. The starting workload of 50 W was increased by 30 W every 3 min until maximal heart rate (HR) was achieved; after a 2-min recovery period at 50 W the test was continued for 15 min at 60% maximal workload. Before and at the end of the test, blood samples were taken for glucose, lactate, and FFA determination. After 1 week, the test was repeated; the volunteers randomly received atenolol or doxazosin for 2 days before the second test. Exercise performance, plasma glucose, and lactate were not affected by either drug. The concentration of FFA was unchanged in subjects treated with doxazosin but was significantly reduced after the test in subjects treated with atenolol. Our data demonstrate that neither doxazosin nor atenolol impairs exercise performance in young volunteers. Atenolol reduces plasma FFA concentration possibly by inhibiting lipolysis. Doxazosin, in contrast, does not alter this parameter. Therefore, doxazosin may be a antihypertensive drug of potential benefit in treatment of hypertensive patients engaging in sports or undergoing a program of physical training.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Near-Infrared Fluorescence Lymphatic Imaging to Reconsider Occlusion Pressure of Superficial Lymphatic Collectors in Upper Extremities of Healthy Volunteers

    PubMed Central

    Vandermeeren, Liesbeth; Vankerckhove, Sophie; Valsamis, Jean-Baptiste; Malloizel-Delaunay, Julie; Moraine, Jean-Jacques; Liebens, Fabienne

    2016-01-01

    Abstract Background: There are very little scientific data on occlusion pressure for superficial lymphatic collectors. Given its importance in determining the transport capacity of lymphatic vessels, it is crucial to know its value. The novel method of near-infrared fluorescence lymphatic imaging (NIRFLI) can be used to visualize lymphatic flow in real time. The goal of this study was to see if this method could be used to measure the lymphatic occlusion pressure. Methods: We observed and recorded lymph flow in the upper limb of healthy volunteers through a transparent cuff using near-infrared fluorescence lymphatic imaging. After obtaining a baseline of the lymph flow without pressure inside the cuff, the cuff was inflated by increments of 10 mm Hg starting at 30 mm Hg. A NIRFLI guided manual lymphatic drainage technique named “Fill & Flush Drainage Method” was performed during the measurement to promote lymph flow. Lymphatic occlusion pressure was determined by observing when lymph flow stopped under the cuff. Results: We measured the lymphatic occlusion pressure on 30 healthy volunteers (11 men and 19 women). Mean lymphatic occlusion pressure in the upper limb was 86 mm Hg (CI ±3.7 mm Hg, α = 0.5%). No significant differences were found between age groups (p = 0.18), gender (p = 0.12), or limb side (p = 0.85). Conclusions: NIRFLI, a transparent sphygmomanometer cuff and the “Fill and Flush” manual lymphatic drainage method were used to measure the lymphatic occlusion pressure in 30 healthy humans. That combination of these techniques allows the visualization of the lymph flow in real time, while ensuring the continuous filling of the lymph collectors during the measurement session, reducing false negative observations. The measured occlusion pressures are much higher than previously described in the medical literature. PMID:27167187

  15. Relationships among fecal daidzein metabolites, dietary habit and BMI in healthy volunteers: a preliminary study

    PubMed Central

    TAMURA, Motoi; HORI, Sachiko; NAKAGAWA, Hiroyuki; KATADA, Kazuhiro; KAMADA, Kazuhiro; UCHIYAMA, Kazuhiko; HANDA, Osamu; TAKAGI, Tomohisa; NAITO, Yuji; YOSHIKAWA, Toshikazu

    2015-01-01

    To investigate the relationships among fecal isoflavone metabolism, dietary habit and Body Mass Index (BMI), 15 healthy men and 15 healthy women were recruited and provided stool samples for analysis of ex vivo anaerobic incubation of fecal suspension with daidzein. A negative correlation was observed between BMI and the dihydrodaidzein (DHD) production in men, and between BMI and the equol production in women. There was a positive correlation between intake of soluble dietary fiber and the DHD production in men. The results suggest that dietary habits and BMI are related to the metabolic activity of isoflavonoids by fecal intestinal microbiota. PMID:26221577

  16. Respiratory responses to laboratory-generation acid fog in healthy and asthmatic volunteers

    SciTech Connect

    Avol, E.L.; Linn, W.S.; Hackney, J.D. )

    1987-01-01

    The authors discuss a program to provide a first step towards assessing acute health-related effects of acid fog exposure. Polluted ambient fog was simulated in a laboratory exposure chamber. Volunteer subjects were purposely exposed and studied during periods of exercise and rest while in the challenge atmosphere. Respiratory responses were measured by methods used to assess effects of irritant gases and dry'' respirable aerosols. When a pilot study showed no obvious unfavorable effects with ambient-like pollution conditions, the exposure concentrations for the present study were extended into the occupational range, well above ambient levels. Sulfuric acid was selected for use as the test pollutant, based upon previous research experience and the availability of fog data documenting its presence during ambient fog episodes.

  17. Pharmacokinetic profile of loprazolam in 12 young and 12 elderly healthy volunteers.

    PubMed

    Dorling, M C; Hindmarch, I

    2001-01-01

    The aim of the study was to investigate the pharmacokinetic profile of acute and steady state doses of loprazolam (1 mg) following nighttime administration in 12 young (18-30 years) and 12 elderly (60-80 years) nonfasting subjects. Loprazolam blood plasma concentration was determined by high-performance liquid chromatography with ultraviolet absorption detection. The drug was isolated from the plasma using a solid phase extraction procedure. On day 1 subjects were breathalyzer and given a brief medical examination. Baseline blood samples (10 ml) were taken via a venous cannula at -1.5 to -0.25 h prior to drug administration. Loprazolam was administered at 21.00 and further blood samples were taken at 0.5, 1, 1.5, 2.0, 2.5, 3, 4, 5, 6, 8, 10, 12, 18 and 23.5 h (baseline sample for day 2). On subsequent days (days 2, 3 and 4) blood samples were taken at -0.5 and 2 h. The schedule for day 1 was repeated for day 5 with the test period ending at 21.30 on day 6. Significant changes in the pharmacokinetics of the drug were evident in the elderly volunteers compared with the young volunteers following steady state, where tmax was significantly prolonged (CI 90% = 0.80 to 1.25; p < 0.00006) and a decline was observed in peak plasma concentration (CI 90% = 0.80 to 1.25; p < 0.00006). However, no statistically significant difference was found between the two groups in either the elimination half-life of the drug or the area under the curve. Loprazolam appears to be well tolerated by both the young and the elderly and only mild adverse effects were reported after nighttime administration. These results provide valuable data on the pharmacokinetics of the drug in normal clinical practice. PMID:11822225

  18. Relationship of echocardiographic indices to pulmonary capillary wedge pressures in healthy volunteers

    NASA Technical Reports Server (NTRS)

    Firstenberg, M. S.; Levine, B. D.; Garcia, M. J.; Greenberg, N. L.; Cardon, L.; Morehead, A. J.; Zuckerman, J.; Thomas, J. D.

    2000-01-01

    OBJECTIVES: We sought to determine the relationship between different echocardiographic indices and pulmonary capillary wedge pressures (PCWP) in normal volunteers. BACKGROUND: Indices based on tissue Doppler (TDE) and color M-mode (CMM) echocardiography have been proposed to reflect left (LV) ventricular filling pressures. These include the ratio of early diastolic transmitral velocity (E) to early myocardial velocity measured by TDE (E') and the ratio of E to the wave propagation velocity (Vp) measured from CMM images. These indices, however, have not been validated in normal individuals. METHODS: We studied seven volunteers during two phases of preload altering maneuvers, baseline, with two stages of lower body negative pressure, and repeat baseline with two stages of volume loading. The PCWP obtained from right heart catheterization was compared with diastolic indices using pulsed Doppler, TDE and CMM echocardiography. RESULTS: The PCWP ranged from 2.2 to 23.5 mm Hg. During preload alterations, significant changes in E and septal E' (both p < 0.05) but not lateral E' or Vp were observed. Furthermore, E, septal E' and E/Vp correlated with PCWP (all r > 0.80) but not combined E and TDE indices (both r < 0.15). Within individuals, a similar linear relationship was observed among E/Vp, E and septal E' (average r > 0.80). CONCLUSIONS: In subjects without heart disease, E, septal E' and E/Vp correlate with PCWP. Because the influence of ventricular relaxation is minimized, the ratio E/Vp may be the best overall index of LV filling pressures.

  19. A sensitive and specific liquid chromatography/tandem mass spectrometry method for determination of pinaverium bromide in human plasma: application to a pharmacokinetic study in healthy volunteers.

    PubMed

    Ren, Jin-Min; Zhao, Xi; Wang, Chuan-Ping; Sun, Qian; Yin, Li-Xin; Zhang, Zhi-Qing

    2011-12-01

    A sensitive and specific method using liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS) for the determination of pinaverium bromide in human plasma was developed and validated. Pinaverium bromide and an internal standard (paclitaxel) were isolated from plasma samples by precipitating plasma, and determined by LC-MS/MS in multiple-reaction monitoring mode. The main metabolite of pinaverium bromide and endogenous substances in plasma did not show any interference. The calibration curve was linear over the plasma concentration range of 10.0-10000.0 pg/mL with a correlation coefficient of 0.9979. The relative standard derivations intra- and inter-day at 30.0, 300.0 and 8000.0 pg/mL in plasma were less than 15%. The absolute recoveries of pinaverium bromide and the internal standard were 99.7-111.7 and 106.2%, respectively. The lower limit of quantitation was 10 pg/mL. The analytical method was successfully applied to study the pharmacokinetics of pinaverium bromide tablets in healthy Chinese volunteers. PMID:21308709

  20. Multiple-exchange-time xenon polarization transfer contrast (MXTC) MRI: initial results in animals and healthy volunteers.

    PubMed

    Dregely, Isabel; Ruset, Iulian C; Mata, Jaime F; Ketel, Jeffrey; Ketel, Steve; Distelbrink, Jan; Altes, Talissa A; Mugler, John P; Wilson Miller, G; William Hersman, F; Ruppert, Kai

    2012-04-01

    Hyperpolarized xenon-129 is a noninvasive contrast agent for lung MRI, which upon inhalation dissolves in parenchymal structures, thus mirroring the gas-exchange process for oxygen in the lung. Multiple-exchange-time xenon polarization transfer contrast (MXTC) MRI is an implementation of the XTC MRI technique in four dimensions (three spatial dimensions plus exchange time). The aim of this study was to evaluate the sensitivity of MXTC MRI for the detection of microstructural deformations of the healthy lung in response to gravity-induced tissue compression and the degree of lung inflation. MXTC MRI was performed in four rabbits and in three healthy human volunteers. Two lung function parameters, one related to tissue- to alveolar-volume ratio and the other to average septal-wall thickness, were determined regionally. A significant gradient in MXTC MRI parameters, consistent with gravity-induced lung tissue deformation in the supine imaging position, was found at low lung volumes. At high lung volumes, parameters were generally lower and the gradient in parameter values was less pronounced. Results show that MXTC MRI permits the quantification of subtle changes in healthy lung microstructure. Further, only structures participating in gas exchange are represented in MXTC MRI data, which potentially makes the technique especially sensitive to pathological changes in lung microstructure affecting gas exchange.

  1. [Effects of aerobic physical conditioning on the profile of plasma lipoproteins in a group of healthy volunteers].

    PubMed

    Ahumada Ayala, M; Cervera, A; Cardoso, G; Sienra, J C; Fernández de la Vega, P; Marin, J; Posadas, C

    1989-01-01

    To evaluate the effects of aerobic physical conditioning on plasma lipoproteins, we studied 26 previously untrained, apparently healthy, non obese volunteers. All participants underwent a treadmill test performed according to the protocol of Bruce with the direct measurement of maximal oxygen consumption (VO2max). A program of aerobic exercise was prescribed for each volunteer at 70% of their corresponding VO2max. At baseline and at the end of weeks 4, 8 and 12 of the exercise program, cholesterol and triglycerides were measured by enzymatic analysis in total plasma and in the lipoprotein fractions separated by preparative ultracentrifugation and precipitation methods. At the end of week 12, the VO2max measurement was repeated. At the end of the protocol, mean VO2max increased from the value of 39.9 observed at baseline to 94.4 ml/kg/min (p less than 0.01). There were no variations in mean body weight, diet or smoking status of the participants during the exercise program. Cholesterol associated with High-density lipoproteins (C-HDL) increased from 42.5 to 46.1 mg/dl (p less than 0.05). This effect was first noticeable at week 8. We didn't observe significant changes in Total Cholesterol nor the Cholesterol fraction associated with Low-density lipoproteins (C-LDL). Total triglycerides decreased at weeks 4 and 8 but returned to near baseline values at week 12. The C-LDL/C-HDL ratio considered as an index of a high coronary risk decreased from 2.32 at baseline to 2.02 (p less than 0.05) at week 12. Thirteen of the twenty six initial volunteers completed the physical conditioning program as planned, the rest were eliminated at different stages of the protocol due to incomplete adherence to their exercise schedules.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Medium light and medium roast paper-filtered coffee increased antioxidant capacity in healthy volunteers: results of a randomized trial.

    PubMed

    Corrêa, Telma Angelina Faraldo; Monteiro, Marcela Piedade; Mendes, Thaíse Maria Nogueira; Oliveira, Daniela Moura de; Rogero, Marcelo Macedo; Benites, Cibelem Iribarrem; Vinagre, Carmen Guilherme Christiano de Matos; Mioto, Bruno Mahler; Tarasoutchi, Daniela; Tuda, Vera Lúcia; César, Luiz Antonio Machado; Torres, Elizabeth Aparecida Ferraz da Silva

    2012-09-01

    We compared the effects of medium light roast (MLR) and medium roast (MR) paper-filtered coffee on antioxidant capacity and lipid peroxidation in healthy volunteers. In a randomized crossover study, 20 volunteers consumed 482 ± 61 ml/day of MLR or MR for four weeks. Plasma total antioxidant status (TAS), oxygen radical absorbance capacity (ORAC), oxidized LDL and 8-epi-prostaglandin F2α, erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activity were measured at baseline and after the interventions. MLR had higher chlorogenic acids-(CGA; 334 mg/150 mL) and less caffeine (231 mg/150 ml) than MR had (210 and 244 mg/150 ml, respectively). MLR also had fewer Maillard reaction products (MRP) than MR had. Compared with baseline, subjects had an increase of 21 and 26 % in TAS, 13 and 13 % in CAT, 52 and 75 % in SOD, and 62 and 49 % in GPx after MLR and MR consumption (P < 0.001), respectively. ORAC increased after MLR (P = 0.004). No significant alteration in lipid peroxidation biomarkers was observed. Both coffees had antioxidant effects. Although MLR contained more CGA, there were similar antioxidant effects between the treatments. MRP may have contributed as an antioxidant. These effects may be important in protecting biological systems and reducing the risk of diseases related to oxidative stress. PMID:22766993

  3. Determination of optimal dosage regimen for amikacin in healthy volunteers by study of pharmacokinetics and bactericidal activity.

    PubMed Central

    Garraffo, R; Drugeon, H B; Dellamonica, P; Bernard, E; Lapalus, P

    1990-01-01

    The pharmacokinetics and serum killing curves of amikacin, which was administered by a 30-minute intravenous infusion of single doses of 7.5 mg/kg and then 15 mg/kg, were investigated in six healthy volunteers who received the two doses in a crossover study with a washout period of 20 days. The serum killing curves were determined for four bacterial species: Escherichia coli, Serratia marcescens, Enterobacter cloacae, and Pseudomonas aeruginosa. All strains were serum resistant, and the bactericidal activity was analyzed by separating the early phase (first 5 h) and the late phase (24 h) of the killing curve. For the early phase, the bactericidal activity was evaluated by correlating an index of surviving bacteria with amikacin concentrations. This methodology allowed determination of two parameters: the maximal effective concentration and the lowest effective concentration. For the late phase, the threshold values separating bacteriostatic and bactericidal activities were lower than 10 mg/liter for each strain. The concentration dependence of amikacin bactericidal activity was confirmed for Escherichia coli and Enterobacter cloacae and, to a lesser extent, for Serratia marcescens and Pseudomonas aeruginosa. Correlation of these data with amikacin pharmacokinetic data in volunteers indicated that a daily dose of 15 mg/kg may be effective in the treatment of Escherichia coli and Enterobacter cloacae infections. For Pseudomonas aeruginosa and Serratia marcescens, the partially time-dependent activity probably necessitates two daily administrations and combination with another antibiotic. PMID:2111658

  4. Cobalt whole blood concentrations in healthy adult male volunteers following two-weeks of ingesting a cobalt supplement.

    PubMed

    Tvermoes, Brooke E; Finley, Brent L; Unice, Kenneth M; Otani, Joanne M; Paustenbach, Dennis J; Galbraith, David A

    2013-03-01

    Recently, there has been an increase in the marketing and sales of dietary supplements, energy drinks, and other consumer products that may contain relatively high concentrations of essential elements. Cobalt-containing supplements are readily available in the U.S. and have been marketed to consumers as energy enhancers. However, little information is available regarding cobalt (Co) body burden and steady-state blood concentrations following the intake of Co dietary supplements. We assessed Co whole blood concentrations in four healthy adult male volunteers who ingested a commercially available Co supplement (0.4 mg Co/day) for 15 or 16 days. Pre-supplementation blood Co concentrations were less than the reporting limit of 0.5 μg/L, consistent with background concentrations reported to range between 0.1 and 0.4 μg/L. The mean whole blood Co concentration in the volunteers after 15 or 16 days of dosing was 3.6 μg Co/L and ranged from 1.8 to 5.1 μg Co/L. The mean observed concentration in the study group was approximately 9-36 times greater than background concentrations. Further studies of Co whole blood concentrations following supplementation over longer time periods with additional monitoring of physiological parameters may provide useful information for evaluating the health of persons who take various doses of Co.

  5. The effects of oral AH 5158, a combined α and β-adrenoceptor antagonist, in healthy volunteers

    PubMed Central

    Richards, D. A.; Woodings, E. P.; Stephens, M. D. B.; Maconochie, J. G.

    1974-01-01

    1 In healthy male volunteers after single oral doses, AH 5158 produced inhibition of exercise induced tachycardia, falls in systolic and diastolic pressure at rest and in response to exercise, which are probably related to combined β- and α-adrenoceptor antagonism. 2 At increasing doses from 100 mg to 400 mg there exists a dose related antagonistic effect, though the dominant effect of β-adrenoceptor antagonism is more easily demonstrable than is α antagonism. 3 As indicated by the pattern of pharmacological effects, absorption of the oral drug is good and the duration of action of a 400 mg dose is approximately 8 hours. 4 Despite being administered in β-adrenoceptor blocking doses, AH 5158 had no adverse effects upon peak expiratory flow at rest or in response to exercise. 5 It is concluded that the pharmacological profile of this combined α- and β-adrenoceptor antagonism suggests a potential therapeutic role as an antihypertensive drug. PMID:22454938

  6. Metabolically Healthy Obesity and Its Associates in Mongolian Chinese Adults

    PubMed Central

    Zhang, Mingzhi; Tong, Weijun; Chen, Jing

    2014-01-01

    Abstract Background: Not all obese individuals show cardiometabolic abnormalities. We examined metabolically healthy obesity (MHO) and its associates in 2530 Mongolian Chinese adults. Methods: MHO was defined by waist circumference, low-density lipoprotein (LDL-C) cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), systolic blood pressure (SBP), diastolic blood pressure (DBP), and glucose. Results: Only 3.0% of the participants had MHO, with 0.8% of men and 4.5% of women having this condition (P<0.001 for sex difference). Despite striking differences in obesity measures, MHO individuals had a comparable cardiometabolic profile to that for metabolically healthy, nonobese individuals (MHNO) and an improved cardiometabolic profile, i.e., lower levels of blood pressure, glucose, insulin, LDL-C, TGs, and higher levels of HDL-C compared to metabolically abnormal individuals (all P<0.01, except for insulin). MHO individuals had lower levels of high-sensitivity C-reactive protein and soluble intercellular adhesion molecule-1, compared to metabolically abnormal individuals, and had comparable levels of these markers to those in MHNO individuals. Furthermore, only 5.3% of MHO individuals had a family history of hypertension, comparable to 5.0% in MHNO individuals, and much lower than 15.9% in metabolically abnormal, nonobese individuals and 12.8% in metabolically abnormal, obese individuals (overall P<0.001). Conclusions: We conclude that MHO is associated with a low inflammation state, and family history of hypertension may play a role in the MHO phenotype. PMID:24460218

  7. Effects of low doses of lorazepam on psychometric tests in healthy volunteers.

    PubMed

    Bourin, M; Couëtoux du Tertre, A; Colombel, M C; Auget, J L

    1994-01-01

    The effects of low oral doses of lorazepam on several cognitive and performance tasks were investigated in 50 healthy students. A double-blind, parallel group design was used to compare five treatments: placebo and lorazepam 0.5, 0.75, 1 mg and progressive doses up to 1.5 mg. After randomization, all subjects received placebo for 3 days in a single-blind procedure followed by five consecutive days of treatment. Subjects completed a battery of tests each day of the 5 days active treatment and the day after stopping the treatment. There were no significant differences between placebo and lorazepam on the free recall test and the critical flicker fusion frequency test, but lorazepam produced significant improvement on the digit symbol substitution test and the choice reaction time test. We suggest that low repeated doses of lorazepam in healthy subjects improve the psychomotor performance without sedation and memory impairment.

  8. Nostrils of healthy volunteers are independent with regard to Staphylococcus aureus carriage.

    PubMed

    Kildow, Beau J; Conradie, Johan P; Robson, Rachel L

    2012-11-01

    The right and left nares of healthy adults (n = 251) were swabbed separately to determine carriage of Staphylococcus aureus in each nostril. Carriers were significantly more likely to carry S. aureus in one nostril than in both. Of those carrying S. aureus in both nostrils, 20% carried genetically distinct strains in each. Nostrils belonging to a single individual should not be assumed to be homogenous with respect to carriage of S. aureus. PMID:22915611

  9. Nostrils of Healthy Volunteers Are Independent with Regard to Staphylococcus aureus Carriage

    PubMed Central

    Kildow, Beau J.; Conradie, Johan P.

    2012-01-01

    The right and left nares of healthy adults (n = 251) were swabbed separately to determine carriage of Staphylococcus aureus in each nostril. Carriers were significantly more likely to carry S. aureus in one nostril than in both. Of those carrying S. aureus in both nostrils, 20% carried genetically distinct strains in each. Nostrils belonging to a single individual should not be assumed to be homogenous with respect to carriage of S. aureus. PMID:22915611

  10. The profile of free amino acids in latent fingerprint of healthy and beta-thalassemic volunteers.

    PubMed

    Khedr, Alaa

    2010-06-01

    The aim of the present work is to apply a non-invasive test, using thumb fingerprint residue analysis, for detection of beta-thalassemia (beta-Thal). The relative percentages of free amino acids (AA) in the latent fingerprint of beta-Thal patients and healthy subjects were compared. The sample included 24 beta-Thal patient and 24 healthy subjects, aged 5-10 years old. Twenty-three AA plus ammonia were analyzed by a sensitive high-performance liquid chromatographic method with fluorescence detection. The profile of AA was calculated based on the percentage of relative amount of each AA to serine (Ser) as it found to be the predominant peak. The statistical and chromatographic profiles of beta-Thal patients were characterized by significant decrease of ornithine, lysine, and zero tyrosine, with significant increase of ammonia, and proline. Other amino acids that exist in low ratios were estimated statistically for significance changes. The relative percentages of each AA of healthy subjects were approximately constant. For this reason, these mentioned AA were assigned as major fingerprint markers of beta-Thal.

  11. Bioequipotency of idraparinux and idrabiotaparinux after once weekly dosing in healthy volunteers and patients treated for acute deep vein thrombosis

    PubMed Central

    Trellu, Marc; Fau, Jean-Baptiste; Cortez, Pierre; Cheng, Sue; Paty, Isabelle; Boëlle, Emmanuelle; Donat, François; Sanderink, Ger-Jan

    2013-01-01

    Aim To assess the bioequipotency of equimolar doses of idraparinux (2.5 mg) and idrabiotaparinux (3.0 mg). Method In a phase I study, 48 healthy male volunteers were randomized to a single subcutaneous injection of idrabiotaparinux or idraparinux, followed by plasma sampling over 27 days. In a prospective substudy of the phase III EQUINOX trial, 228 patients treated for acute symptomatic deep vein thrombosis received idrabiotaparinux or idraparinux once weekly for 6 months. Plasma sampling was performed within 5 days following the last injection. The primary pharmacodynamic endpoint was the inhibition of activated factor X (FXa) activity. Maximal anti-FXa activity (Amax) and area under anti-FXa activity vs. time curve (AAUC) were calculated. Safety and tolerability were also assessed. Results In both studies, pharmacodynamic anti-FXa vs. time profiles of idrabiotaparinux and idraparinux were superimposable. Ratio estimates (90% confidence intervals [CIs]) for idrabiotaparinux : idraparinux were 0.96 (0.89, 1.04) for Amax and 0.95 (0.87, 1.04) for AAUC in the phase I study, and 1.11 (1.00, 1.22) for Amax and 1.06 (0.96, 1.16) for AAUC at month 6 in the EQUINOX substudy. Idrabiotaparinux and idraparinux were considered bioequipotent because 90% CIs were within the pre-specified interval (0.80, 1.25). Study treatments were well tolerated. Conclusion Pharmacodynamic parameters reported after single dose in healthy volunteers and after repeated once weekly dosing in patients demonstrated the bioequipotency of idrabiotaparinux and idraparinux based on FXa inhibition. These outcomes support the use of an idrabiotaparinux dose bioequipotent to an idraparinux dose in large clinical trials, and the possibility to substitute idrabiotaparinux to idraparinux for the treatment of venous thromboembolism. PMID:23078631

  12. Effects of Oral Lycopene Supplementation on Vascular Function in Patients with Cardiovascular Disease and Healthy Volunteers: A Randomised Controlled Trial

    PubMed Central

    Gajendragadkar, Parag R.; Hubsch, Annette; Mäki-Petäjä, Kaisa M.; Serg, Martin; Wilkinson, Ian B.; Cheriyan, Joseph

    2014-01-01

    Aims The mechanisms by which a ‘Mediterranean diet’ reduces cardiovascular disease (CVD) burden remain poorly understood. Lycopene is a potent antioxidant found in such diets with evidence suggesting beneficial effects. We wished to investigate the effects of lycopene on the vasculature in CVD patients and separately, in healthy volunteers (HV). Methods and Results We randomised 36 statin treated CVD patients and 36 healthy volunteers in a 2∶1 treatment allocation ratio to either 7 mg lycopene or placebo daily for 2 months in a double-blind trial. Forearm responses to intra-arterial infusions of acetylcholine (endothelium-dependent vasodilatation; EDV), sodium nitroprusside (endothelium-independent vasodilatation; EIDV), and NG-monomethyl-L-arginine (basal nitric oxide (NO) synthase activity) were measured using venous plethysmography. A range of vascular and biochemical secondary endpoints were also explored. EDV in CVD patients post-lycopene improved by 53% (95% CI: +9% to +93%, P = 0.03 vs. placebo) without changes to EIDV, or basal NO responses. HVs did not show changes in EDV after lycopene treatment. Blood pressure, arterial stiffness, lipids and hsCRP levels were unchanged for lycopene vs. placebo treatment groups in the CVD arm as well as the HV arm. At baseline, CVD patients had impaired EDV compared with HV (30% lower; 95% CI: −45% to −10%, P = 0.008), despite lower LDL cholesterol (1.2 mmol/L lower, 95% CI: −1.6 to −0.9 mmol/L, P<0.001). Post-therapy EDV responses for lycopene-treated CVD patients were similar to HVs at baseline (2% lower, 95% CI: −30% to +30%, P = 0.85), also suggesting lycopene improved endothelial function. Conclusions Lycopene supplementation improves endothelial function in CVD patients on optimal secondary prevention, but not in HVs. Trial Registration ClinicalTrials.gov NCT01100385 PMID:24911964

  13. Contrast and glare sensitivity in epilepsy patients treated with vigabatrin or carbamazepine monotherapy compared with healthy volunteers

    PubMed Central

    Nousiainen, I.; Kalviainen, R.; Mantyjarvi, M.

    2000-01-01

    BACKGROUND/AIM—Many antiepileptic drugs have influence on visual functions. The aim of this study was to investigate possible changes in contrast sensitivity, macular photostress, and brightness acuity (glare) tests in patients with epilepsy undergoing vigabatrin (VGB) or carbamazepine (CBZ) monotherapy compared with healthy volunteers.
METHODS—32 patients undergoing VGB therapy, 18 patients undergoing CBZ therapy, and 35 healthy volunteers were asked to participate in an ophthalmological examination. In the previous study, visual field constrictions were reported in 40% of the patients treated with VGB monotherapy. In the present study, these VGB and CBZ monotherapy patients were examined for photopic contrast sensitivity with the Pelli-Robson letter chart and brightness acuity and macular photostress with the Mentor BAT brightness acuity tester.
RESULTS—Contrast sensitivity with the Pelli-Robson letter chart showed no difference between these groups and normal subjects (ANOVA: p= 0.534 in the right eye, p= 0.692 in the left eye) but the VGB therapy patients showed a positive correlation between the contrast sensitivity values and the extents of the visual fields in linear regression (R = 0.498, p = 0.05 in the right eye, R = 0.476, p = 0.06 in the left eye). Macular photostress and glare tests were equal in both groups and did not differ from normal values.
CONCLUSION—The results of this study indicate that carbamazepine therapy has no effect on contrast sensitivity. Vigabatrin seems to impair contrast sensitivity in those patients who have concentrically constricted in their visual fields. Neither GBZ nor VGB affect glare sensitivity.

 PMID:10837389

  14. Near-infrared spectroscopy extended with indocyanine green dye dilution for cerebral blood flow measurement: Median values in healthy volunteers

    NASA Astrophysics Data System (ADS)

    Mudra, R.; Muroi, C.; Niederer, P.; Keller, E.

    2008-09-01

    The cerebral blood flow (CBF) is an important vital parameter in neurointensive care. Currently, there is no non-invasive method for its measurement that can easily be applied at the bedside. A new tool to determine CBF is based on near-infrared spectroscopy (NIRS) applied together with indocyanine green (ICG) dye dilution. From a bilateral measurement on selected regions on the head of infrared (IR) absorption at various wavelengths during the dilution maneuver, the vascular perfusion characteristics of the two brain hemispheres can be determined in terms of mean transit time (mtt) of ICG, cerebral blood volume (CBV) and CBF. So far, on nine healthy volunteers, NIRS ICG dye dilution bihemispheric measurements were performed, which yielded to mtt given as median (range) of 9.3 s (5.1-16.3 s), CBV of 3.5 ml/100 g (1.7-4.1 ml/100 g), and CBF of 18.2 ml/(100 g×min) [11.1-48.6 ml/(100 g×min)]. Additionally, the blood flow index (BFI) was calculated with BFI= 13.8 mg/(100 g×s) [6.6-15.2 mg/(100 g×s)]. The Spearman rank correlation coefficient between CBF and BFI was RS = 0.76. However, as the Bland & Altman plot between CBFNIRS and the CBFBFI documents, the limits of agreement are rather wide (21.9±6.7). Under physiological conditions in healthy volunteers, no differences could be detected between the hemispheres.

  15. Inhaled loxapine and intramuscular lorazepam in healthy volunteers: a randomized placebo-controlled drug-drug interaction study.

    PubMed

    Spyker, Daniel A; Cassella, James V; Stoltz, Randall R; Yeung, Paul P

    2015-12-01

    Pharmacodynamic effects and safety of single-dose inhaled loxapine administered via the Staccato(®) system and intramuscular (IM) lorazepam in combination versus each agent alone were compared in a randomized, double-blind, crossover study in healthy volunteers. Subjects received: inhaled loxapine 10 mg + IM lorazepam 1 mg; inhaled loxapine 10 mg + IM placebo; IM lorazepam 1 mg + Staccato placebo in random order, each separated by a 3-day washout. Primary endpoints were maximum effect (minimum value) and area under the curve (AUC) from baseline to 2 h post treatment for respirations/min and pulse oximetry. Least-squares means (90% confidence interval [CI]) for concomitant treatment versus each agent alone were derived and equivalence (no difference) confirmed if the 90% CI was within 0.8-1.25. Blood pressure (BP), heart rate (HR), sedation (100-mm visual analog scale), and adverse events (AEs) were recorded. All 18 subjects (mean age, 20.4 years; 61% male) completed the study. There was no difference between inhaled loxapine + IM lorazepam and either agent alone on respiration or pulse oximetery during the 12-h postdose period, confirmed by 90% CIs for AUC and C min ratios. BP and HR were no different for inhaled loxapine + IM lorazepam and each agent alone over a 12-h postdose period. Although the central nervous system sedative effects were observed for each treatment in healthy volunteers, the effect was greater following concomitant lorazepam 1 mg IM + inhaled loxapine 10 mg administration. There were no deaths, serious AEs, premature discontinuations due to AEs, or treatment-related AEs. PMID:27022468

  16. Evaluation of the pharmacokinetics and pharmacodynamics of ticagrelor co-administered with aspirin in healthy volunteers.

    PubMed

    Teng, Renli; Maya, Juan; Butler, Kathleen

    2013-01-01

    The results of two independent, randomized, two-period crossover, single-center studies, conducted to assess the pharmacokinetics of ticagrelor ± aspirin, inhibition of platelet aggregation (IPA) with ticagrelor/aspirin vs. clopidogrel/aspirin, and safety, tolerability, and bleeding times are reported here. In Study A (open-label), 16 volunteers received ticagrelor (50 mg bid Days 1-5; 200 mg bid Days 6-9; one 200 mg dose on Day 10) ± 300 mg qd aspirin (Days 1-10). In Study B (double-blind, double-dummy), 16 volunteers received aspirin (300 mg loading dose/75 mg qd Days 2-9) with either ticagrelor (200 mg bid Days 4-8, one 200 mg dose on Day 9) or clopidogrel (300 mg loading dose Day 4, 75 mg qd Days 5-9). At steady-state ticagrelor (50 mg bid, or 200 mg bid), concomitant aspirin (300 mg qd) had no effect on mean maximum plasma concentration (Cmax), median time to Cmax (tmax), or mean area under the plasma concentration-time curve for the dosing interval (AUC0-τ) for ticagrelor and its primary metabolite, AR-C124910XX. Following 200 mg bid ticagrelor, mean Cmax and AUC0-τ for both parent and metabolite were comparable with co-administration of aspirin at 75 mg and 300 mg qd. Aspirin (300 mg qd) had no effect on IPA (ADP-induced) by ticagrelor. However, aspirin and ticagrelor had an additive effect on IPA (collagen-induced). Ticagrelor/aspirin increased bleeding times vs. baseline. Ticagrelor/aspirin co-administration was well tolerated at all dose combinations evaluated. In summary, the findings of this study demonstrate that co-administration of aspirin (300 mg qd) with ticagrelor (50 mg bid, or 200 mg bid) had no effect on ticagrelor pharmacokinetics or IPA (ADP-induced) by ticagrelor. PMID:23249161

  17. Cooking Healthy, Eating Smart (CHES): Evaluating the feasibility of using volunteers to deliver nutrition and food safety education to rural older adults

    NASA Astrophysics Data System (ADS)

    Getty, Morgan

    Due to their limited resources, rural, older adults in the United States are at risk for poor diet-related health outcomes. Nutrition education is a key component in improving health outcomes in older adults. Cooking Healthy, Eating Smart (CHES) is a nine-lesson curriculum designed to teach rural, older adults culturally appropriate nutrition and food safety information. Funding to hire health professionals to deliver such a curriculum is limited, presenting the need to explore a less expensive mode of dissemination. In this community-based, participatory research study, a formative evaluation and feasibility study were conducted to examine the use of volunteers to deliver a nutrition and food safety curriculum to rural, older adults in South Carolina. Seven focus groups were conducted with members of the South Carolina Family and Community Leaders (SCFCL) and members of the American Association of Retired Persons (AARP) in the four regions of South Carolina to explore barriers and facilitators of volunteers delivering CHES (N=65 participants). The focus group findings informed the development of the volunteer training manual. A comparative case study method was used to examine the feasibility of a volunteer-based approach by observing and describing the delivery of CHES by two groups of volunteers in SC. The case study findings, including volunteer knowledge change, self-efficacy change, curriculum experience, program experience, and project team observations of volunteers indicated that using volunteers to deliver CHES is a plausible approach with the assistance of paid staff or project team members.

  18. Global Methylation and Hydroxymethylation in DNA from Blood and Saliva in Healthy Volunteers.

    PubMed

    Godderis, Lode; Schouteden, Caroline; Tabish, Ali; Poels, Katrien; Hoet, Peter; Baccarelli, Andrea A; Van Landuyt, Kirsten

    2015-01-01

    Aims. We describe a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify and compare simultaneously global methylation and hydroxymethylation in human DNA of different tissues. Materials and Methods. Blood and saliva DNA from fourteen volunteers was processed for epigenetic endpoints using LC-MS/MS and PCR-pyrosequencing technology. Results. Global DNA methylation was significantly lower in saliva (mean 4.61% ±  0.80%), compared to blood samples (5.70% ± 0.22%). In contrast, saliva (0.036% ± 0.011%) revealed significantly higher hydroxymethylation compared to blood samples (mean 0.027% ± 0.004%). Whereas we did not find significant correlations for both epigenetic measures between the tissues, a significant association was observed between global methylation and global hydroxymethylation in saliva DNA. Neither LINE-1 nor Alu elements of blood and saliva correlated, nor were they correlated with the DNA hydroxymethylation of blood or saliva, respectively. Conclusion. Global DNA methylation and hydroxymethylation of cytosine can be quantified simultaneously by LC-MS/MS. Saliva DNA cannot be considered as a surrogate for blood DNA to study epigenetic endpoints.

  19. Acid fog: effects on respiratory function and symptoms in healthy and asthmatic volunteers

    SciTech Connect

    Hackney, J.D.; Linn, W.S.; Avol, E.L.

    1989-02-01

    Acidic air pollutants generally are dissolved in water droplets. Mean droplet diameter may range from more than 10 microns in dense fog to less than 1 micron at low relative humidity. Droplet size influences the deposition of inhaled acid within the respiratory tract and thus may influence toxicity. To help assess health risks from acid pollution, we performed controlled exposures of normal and asthmatic volunteers to sulfuric acid aerosols at nominal concentrations of 0 (control), 500, 1000, and 2000 micrograms/m/sup 3/. Exposures lasted 1 hr with intermittent heavy exercise. Response was assessed by lung function tests and symptom questionnaires. Under foggy conditions (mean droplet size 10 microns, temperature 50 degrees F), no marked effects on lung function were found. However, both normal and asthmatic subjects showed statistically significant dose-related increases in respiratory symptoms. In a separate study, normal subjects exposed at 70 degrees F with mean droplet size 0.9 microns showed no marked effect on function or symptoms. Asthmatics showed dose-related decrements in forced expiratory performance and increases in symptoms, most obvious at 1000 and 2000 micrograms/m/sup 3/. The different results of the two studies probably reflect an influence of droplet size, but further investigation is needed to confirm this. The aggregate results suggest that only mild, if any, short-term respiratory irritant effects are likely at acid concentrations attained in ambient pollution.

  20. Acid fog: effects on respiratory function and symptoms in healthy and asthmatic volunteers.

    PubMed

    Hackney, J D; Linn, W S; Avol, E L

    1989-02-01

    Acidic air pollutants generally are dissolved in water droplets. Mean droplet diameter may range from more than 10 microns in dense fog to less than 1 micron at low relative humidity. Droplet size influences the deposition of inhaled acid within the respiratory tract and thus may influence toxicity. To help assess health risks from acid pollution, we performed controlled exposures of normal and asthmatic volunteers to sulfuric acid aerosols at nominal concentrations of 0 (control), 500, 1000, and 2000 micrograms/m3. Exposures lasted 1 hr with intermittent heavy exercise. Response was assessed by lung function tests and symptom questionnaires. Under foggy conditions (mean droplet size 10 microns, temperature 50 degrees F), no marked effects on lung function were found. However, both normal and asthmatic subjects showed statistically significant dose-related increases in respiratory symptoms. In a separate study, normal subjects exposed at 70 degrees F with mean droplet size 0.9 microns showed no marked effect on function or symptoms. Asthmatics showed dose-related decrements in forced expiratory performance and increases in symptoms, most obvious at 1000 and 2000 micrograms/m3. The different results of the two studies probably reflect an influence of droplet size, but further investigation is needed to confirm this. The aggregate results suggest that only mild, if any, short-term respiratory irritant effects are likely at acid concentrations attained in ambient pollution.

  1. Airflow Dynamics of Coughing in Healthy Human Volunteers by Shadowgraph Imaging: An Aid to Aerosol Infection Control

    PubMed Central

    Tang, Julian W.; Nicolle, Andre; Pantelic, Jovan; Koh, Gerald C.; Wang, Liang De; Amin, Muhammad; Klettner, Christian A.; Cheong, David K. W.; Sekhar, Chandra; Tham, Kwok Wai

    2012-01-01

    Cough airflow dynamics have been previously studied using a variety of experimental methods. In this study, real-time, non-invasive shadowgraph imaging was applied to obtain additional analyses of cough airflows produced by healthy volunteers. Twenty healthy volunteers (10 women, mean age 32.2±12.9 years; 10 men, mean age 25.3±2.5 years) were asked to cough freely, then into their sleeves (as per current US CDC recommendations) in this study to analyze cough airflow dynamics. For the 10 females (cases 1–10), their maximum detectable cough propagation distances ranged from 0.16–0.55 m, with maximum derived velocities of 2.2–5.0 m/s, and their maximum detectable 2-D projected areas ranged from 0.010–0.11 m2, with maximum derived expansion rates of 0.15–0.55 m2/s. For the 10 males (cases 11–20), their maximum detectable cough propagation distances ranged from 0.31–0.64 m, with maximum derived velocities of 3.2–14 m/s, and their maximum detectable 2-D projected areas ranged from 0.04–0.14 m2, with maximum derived expansion rates of 0.25–1.4 m2/s. These peak velocities were measured when the visibility of the exhaled airflows was optimal and compare favorably with those reported previously using other methods, and may be seen as a validation of these previous approaches in a more natural setting. However, the propagation distances can only represent a lower limit due to the inability of the shadowgraph method to visualize these cough airflows once their temperature cools to that of the ambient air, which is an important limitation of this methodology. The qualitative high-speed video footage of these volunteers coughing into their sleeves demonstrates that although this method rarely completely blocks the cough airflow, it decelerates, splits and redirects the airflow, eventually reducing its propagation. The effectiveness of this intervention depends on optimum positioning of the arm over the nose and mouth during coughing, though unsightly stains

  2. Population pharmacokinetic analysis of isoniazid, acetylisoniazid, and isonicotinic acid in healthy volunteers.

    PubMed

    Seng, Kok-Yong; Hee, Kim-Hor; Soon, Gaik-Hong; Chew, Nicholas; Khoo, Saye H; Lee, Lawrence Soon-U

    2015-11-01

    In this study, we aimed to quantify the effects of the N-acetyltransferase 2 (NAT2) phenotype on isoniazid (INH) metabolism in vivo and identify other sources of pharmacokinetic variability following single-dose administration in healthy Asian adults. The concentrations of INH and its metabolites acetylisoniazid (AcINH) and isonicotinic acid (INA) in plasma were evaluated in 33 healthy Asians who were also given efavirenz and rifampin. The pharmacokinetics of INH, AcINH, and INA were analyzed using nonlinear mixed-effects modeling (NONMEM) to estimate the population pharmacokinetic parameters and evaluate the relationships between the parameters and the elimination status (fast, intermediate, and slow acetylators), demographic status, and measures of renal and hepatic function. A two-compartment model with first-order absorption best described the INH pharmacokinetics. AcINH and INA data were best described by a two- and a one-compartment model, respectively, linked to the INH model. In the final model for INH, the derived metabolic phenotypes for NAT2 were identified as a significant covariate in the INH clearance, reducing its interindividual variability from 86% to 14%. The INH clearance in fast eliminators was 1.9- and 7.7-fold higher than in intermediate and slow eliminators, respectively (65 versus 35 and 8 liters/h). Creatinine clearance was confirmed as a significant covariate for AcINH clearance. Simulations suggested that the current dosing guidelines (200 mg for 30 to 45 kg and 300 mg for >45 kg) may be suboptimal (3 mg/liter ≤ Cmax ≤ 6 mg/liter) irrespective of the acetylator class. The analysis established a model that adequately characterizes INH, AcINH, and INA pharmacokinetics in healthy Asians. Our results refine the NAT2 phenotype-based predictions of the pharmacokinetics for INH.

  3. Ultrasonographic Measurement of the Thickness of Axillary Recess Capsule in Healthy Volunteers

    PubMed Central

    2016-01-01

    Objective To evaluate the inter-rater and intra-rater reliability of ultrasonographic measurements of axillary recess (AR) thickness in healthy individuals, and to analyze the factors affecting the thickness of the AR capsule. Methods We recruited 20 healthy individuals (10 male, 10 female) with a mean age of 37 years (standard deviation ±10). Two physiatrists (an experienced and a novice rater) independently investigated the AR thickness in three rounds. The AR thickness was measured for each individual at three shoulder abduction angles (50°, 70°, and 90°). Intra-class correlation (ICC) coefficients were used to assess the reproducibility of each measurement. Results Excellent intra-rater reliability coefficients were observed at the three shoulder abduction angles, in the analysis of both raters. The inter-rater reliability coefficient was also was excellent in both studies. There were significant differences in the AR thickness, according to the angle of shoulder abduction. The AR was thicker at 50° than at 70° and 90° (all p<0.001), and the AR was thicker at 70° than at 90° (p<0.001). Height (r=0.62, p=0.003) and body mass index (r=0.52, p=0.019) were positively correlated with AR thickness. Males had a thicker AR capsule than females at all three angles (all p<0.001). Conclusion Ultrasonographic measurements of AR thickness in healthy individuals demonstrate excellent intra-rater and inter-rater reliability. AR thickness may depend on anthropometric variables and position of the shoulder. PMID:27446788

  4. Single dose pharmacokinetics of the novel transdermal donepezil patch in healthy volunteers

    PubMed Central

    Kim, Yo Han; Choi, Hee Youn; Lim, Hyeong-Seok; Lee, Shi Hyang; Jeon, Hae Sun; Hong, Donghyun; Kim, Seong Su; Choi, Young Kweon; Bae, Kyun-Seop

    2015-01-01

    Background Donepezil is an acetylcholinesterase inhibitor indicated for Alzheimer’s disease. The aim of this randomized, single-blind, placebo-controlled, single-dose, dose-escalation study was to investigate the safety, tolerability, and pharmacokinetics of the donepezil patch in healthy male subjects. Methods Each healthy male subject received a single transdermal donepezil patch (72 hours patch-on periods) of 43.75 mg/12.5 cm2, 87.5 mg/25 cm2, or 175 mg/50 cm2. Serial blood samples were collected up to 312 hours after patch application. The plasma concentrations of donepezil were determined by using a validated liquid chromatography–tandem mass spectrometry method. Pharmacokinetic parameters were obtained by noncompartmental analysis. Tolerability of the patches and performance of the patches (adhesion, skin irritation, residual donepezil content in the patch) were assessed throughout the study. Results The study was completed by 36 healthy subjects. After patch application, the maximal plasma donepezil concentration (Cmax) and the area under the curve (AUC) increased in a dose-proportional manner. Median time to Cmax was ~74–76 hours (~2–4 hours after patch removal), and mean t1/2β was ~63.77–93.07 hours. The average donepezil residue in the patch after 72 hours was ~73.9%–86.7% of the loading dose. There were neither serious adverse events nor adverse events that lead to discontinuation. Skin adhesion of the patch was good in 97.2% of the subjects. All skin irritations after patch removal were mild and were resolved during the study period. Conclusion The donepezil patch appeared to be generally well tolerated and adhesive. Pharmacokinetic analysis of the donepezil patch demonstrated linear kinetics. PMID:25792802

  5. Blood and breath levels of selected volatile organic compounds in healthy volunteers

    PubMed Central

    King, Julian; Klieber, Martin; Unterkofler, Karl; Hinterhuber, Hartmann; Baumann, Matthias

    2016-01-01

    Gas chromatography with mass spectrometric detection (GC-MS) was used to identify and quantify volatile organic compounds in the blood and breath of healthy individuals. Blood and breath volatiles were preconcentrated using headspace solid phase micro-extraction (HS-SPME) and needle trap devices (NTDs), respectively. The study involved a group of 28 healthy test subjects and resulted in the quantification of a total of 74 compounds in both types of samples. The concentrations of the species under study varied between 0.01 and 6700 nmol L−1 in blood and between 0.02 and 2500 ppb in exhaled air. Limits of detection (LOD) ranged from 0.01 to 270 nmol L−1 for blood compounds and from 0.01 to 0.7 ppb for breath species. Relative standard deviations for both measurement regimes varied from 1.5 to 14%. The predominant chemical classes among the compounds quantified were hydrocarbons (24), ketones (10), terpenes (8), heterocyclic compounds (7) and aromatic compounds (7). Twelve analytes were found to be highly present in both blood and exhaled air (with incidence rates higher than 80%) and for 32 species significant differences (Wilcoxon signed-rank test) between room air and exhaled breath were observed. By comparing blood, room air and breath levels in parallel, a tentative classification of volatiles into endogenous and exogenous compounds can be achieved. PMID:23435188

  6. Microdosing of a Carbon-14 Labeled Protein in Healthy Volunteers Accurately Predicts Its Pharmacokinetics at Therapeutic Dosages.

    PubMed

    Vlaming, M L H; van Duijn, E; Dillingh, M R; Brands, R; Windhorst, A D; Hendrikse, N H; Bosgra, S; Burggraaf, J; de Koning, M C; Fidder, A; Mocking, J A J; Sandman, H; de Ligt, R A F; Fabriek, B O; Pasman, W J; Seinen, W; Alves, T; Carrondo, M; Peixoto, C; Peeters, P A M; Vaes, W H J

    2015-08-01

    Preclinical development of new biological entities (NBEs), such as human protein therapeutics, requires considerable expenditure of time and costs. Poor prediction of pharmacokinetics in humans further reduces net efficiency. In this study, we show for the first time that pharmacokinetic data of NBEs in humans can be successfully obtained early in the drug development process by the use of microdosing in a small group of healthy subjects combined with ultrasensitive accelerator mass spectrometry (AMS). After only minimal preclinical testing, we performed a first-in-human phase 0/phase 1 trial with a human recombinant therapeutic protein (RESCuing Alkaline Phosphatase, human recombinant placental alkaline phosphatase [hRESCAP]) to assess its safety and kinetics. Pharmacokinetic analysis showed dose linearity from microdose (53 μg) [(14) C]-hRESCAP to therapeutic doses (up to 5.3 mg) of the protein in healthy volunteers. This study demonstrates the value of a microdosing approach in a very small cohort for accelerating the clinical development of NBEs. PMID:25869840

  7. From neural signatures of emotional modulation to social cognition: individual differences in healthy volunteers and psychiatric participants.

    PubMed

    Ibáñez, Agustín; Aguado, Jaume; Baez, Sandra; Huepe, David; Lopez, Vladimir; Ortega, Rodrigo; Sigman, Mariano; Mikulan, Ezequiel; Lischinsky, Alicia; Torrente, Fernando; Cetkovich, Marcelo; Torralva, Teresa; Bekinschtein, Tristan; Manes, Facundo

    2014-07-01

    It is commonly assumed that early emotional signals provide relevant information for social cognition tasks. The goal of this study was to test the association between (a) cortical markers of face emotional processing and (b) social-cognitive measures, and also to build a model which can predict this association (a and b) in healthy volunteers as well as in different groups of psychiatric patients. Thus, we investigated the early cortical processing of emotional stimuli (N170, using a face and word valence task) and their relationship with the social-cognitive profiles (SCPs, indexed by measures of theory of mind, fluid intelligence, speed processing and executive functions). Group comparisons and individual differences were assessed among schizophrenia (SCZ) patients and their relatives, individuals with attention deficit hyperactivity disorder (ADHD), individuals with euthymic bipolar disorder (BD) and healthy participants (educational level, handedness, age and gender matched). Our results provide evidence of emotional N170 impairments in the affected groups (SCZ and relatives, ADHD and BD) as well as subtle group differences. Importantly, cortical processing of emotional stimuli predicted the SCP, as evidenced by a structural equation model analysis. This is the first study to report an association model of brain markers of emotional processing and SCP.

  8. Horse meat consumption affects iron status, lipid profile and fatty acid composition of red blood cells in healthy volunteers.

    PubMed

    Del Bó, Cristian; Simonetti, Paolo; Gardana, Claudio; Riso, Patrizia; Lucchini, Giorgio; Ciappellano, Salvatore

    2013-03-01

    This study investigated the effect of moderate consumption of horse meat on iron status, lipid profile and fatty acid composition of red blood cells in healthy male volunteers. Fifty-two subjects were randomly assigned to two groups of 26 subjects each: a test group consuming two portions of 175 g/week of horse meat, and a control group that abstained from eating horse meat during the 90 days trial. Before and after 90 days, blood samples were collected for analysis. Horse meat consumption significantly (p ≤ 0.05) reduced serum levels of total and low-density lipoprotein cholesterol ( - 6.2% and - 9.1%, respectively) and transferrin ( - 4.6%). Total n - 3, long chain polyunsaturated fatty acids n - 3 and docosahexeanoic acid content in erythrocytes increased (p ≤ 0.05) by about 7.8%, 8% and 11%, respectively. In conclusion, the regular consumption of horse meat may contribute to the dietary intake of n - 3 polyunsaturated fatty acids and may improve lipid profile and iron status in healthy subjects.

  9. From neural signatures of emotional modulation to social cognition: individual differences in healthy volunteers and psychiatric participants

    PubMed Central

    Aguado, Jaume; Baez, Sandra; Huepe, David; Lopez, Vladimir; Ortega, Rodrigo; Sigman, Mariano; Mikulan, Ezequiel; Lischinsky, Alicia; Torrente, Fernando; Cetkovich, Marcelo; Torralva, Teresa; Bekinschtein, Tristan; Manes, Facundo

    2014-01-01

    It is commonly assumed that early emotional signals provide relevant information for social cognition tasks. The goal of this study was to test the association between (a) cortical markers of face emotional processing and (b) social-cognitive measures, and also to build a model which can predict this association (a and b) in healthy volunteers as well as in different groups of psychiatric patients. Thus, we investigated the early cortical processing of emotional stimuli (N170, using a face and word valence task) and their relationship with the social-cognitive profiles (SCPs, indexed by measures of theory of mind, fluid intelligence, speed processing and executive functions). Group comparisons and individual differences were assessed among schizophrenia (SCZ) patients and their relatives, individuals with attention deficit hyperactivity disorder (ADHD), individuals with euthymic bipolar disorder (BD) and healthy participants (educational level, handedness, age and gender matched). Our results provide evidence of emotional N170 impairments in the affected groups (SCZ and relatives, ADHD and BD) as well as subtle group differences. Importantly, cortical processing of emotional stimuli predicted the SCP, as evidenced by a structural equation model analysis. This is the first study to report an association model of brain markers of emotional processing and SCP. PMID:23685775

  10. Payments to Normal Healthy Volunteers in Phase 1 Trials: Avoiding Undue Influence While Distributing Fairly the Burdens of Research Participation

    PubMed Central

    2009-01-01

    Clinical investigators must engage in just subject recruitment and selection and avoid unduly influencing research participation. There may be tension between the practice of keeping payments to participants low to avoid undue influence and the requirements of justice when recruiting normal healthy volunteers for phase 1 drug studies. By intentionally keeping payments low to avoid unduly influenced participation, investigators, on the recommendation or insistence of institutional review boards, may be targeting or systematically recruiting healthy adult members of lower socio-economic groups for participation in phase 1 studies. Investigators are at risk of routinely failing to fulfill the obligation of justice, which prohibits the systematic targeting and recruiting of subjects for reasons unrelated to the nature of the study. Insofar as we take seriously the obligation to engage in just subject recruitment and selection, I argue that we must acknowledge the implications low payments might have for subject recruitment and selection and examine the effect of low payments. If low payments de facto target the less well-off for phase 1 studies, we must defend the priority ranking of the obligation to avoid undue influence over the obligation of justice or adopt an alternative recruitment approach. This paper identifies a number of alternatives to the current system of low-value payments to research participants. PMID:19190076

  11. The Effects of Smoking on Levels of Endothelial Progenitor Cells and Microparticles in the Blood of Healthy Volunteers

    PubMed Central

    Mobarrez, Fariborz; Antoniewicz, Lukasz; Bosson, Jenny A.; Kuhl, Jeanette; Pisetsky, David S.; Lundbäck, Magnus

    2014-01-01

    Background Cigarette smoking, both active and passive, is one of the leading causes of morbidity and mortality in cardiovascular disease. To assess the impact of brief smoking on the vasculature, we determined levels of circulating endothelial progenitor cells (EPCs) and circulating microparticles (MPs) following the smoking of one cigarette by young, healthy intermittent smokers. Materials and Methods 12 healthy volunteers were randomized to either smoking or not smoking in a crossover fashion. Blood sampling was performed at baseline, 1, 4 and 24 hours following smoking/not smoking. The numbers of EPCs and MPs were determined by flow cytometry. MPs were measured from platelets, leukocytes and endothelial cells. Moreover, MPs were also labelled with anti-HMGB1 and SYTO 13 to assess the content of nuclear molecules. Results Active smoking of one cigarette caused an immediate and significant increase in the numbers of circulating EPCs and MPs of platelet-, endothelial- and leukocyte origin. Levels of MPs containing nuclear molecules were increased, of which the majority were positive for CD41 and CD45 (platelet- and leukocyte origin). CD144 (VE-cadherin) or HMGB1 release did not significantly change during active smoking. Conclusion Brief active smoking of one cigarette generated an acute release of EPC and MPs, of which the latter contained nuclear matter. Together, these results demonstrate acute effects of cigarette smoke on endothelial, platelet and leukocyte function as well as injury to the vascular wall. PMID:24587320

  12. Expectation-induced placebo responses fail to accelerate wound healing in healthy volunteers: results from a prospective controlled experimental trial.

    PubMed

    Vits, Sabine; Dissemond, Joachim; Schadendorf, Dirk; Kriegler, Lisa; Körber, Andreas; Schedlowski, Manfred; Cesko, Elvir

    2015-12-01

    Placebo responses have been shown to affect the symptomatology of skin diseases. However, expectation-induced placebo effects on wound healing processes have not been investigated yet. We analysed whether subjects' expectation of receiving an active drug accelerates the healing process of experimentally induced wounds. In 22 healthy men (experimental group, n = 11; control group, n = 11) wounds were induced by ablative laser on both thighs. Using a deceptive paradigm, participants in the experimental group were informed that an innovative 'wound gel' was applied on one of the two wounds, whereas a 'non-active gel' was applied on the wound of the other thigh. In fact, both gels were identical hydrogels without any active components. A control group was informed to receive a non-active gel on both wounds. Progress in wound healing was documented via planimetry on days 1, 4 and 7 after wound induction. From day 9 onwards wound inspections were performed daily accompanied by a change of the dressing and a new application of the gel. No significant differences could be observed with regard to duration or process of wound healing, either by intraindividual or by interindividual comparisons. These data document no expectation-induced placebo effect on the healing process of experimentally induced wounds in healthy volunteers. PMID:24373522

  13. Expectation-induced placebo responses fail to accelerate wound healing in healthy volunteers: results from a prospective controlled experimental trial.

    PubMed

    Vits, Sabine; Dissemond, Joachim; Schadendorf, Dirk; Kriegler, Lisa; Körber, Andreas; Schedlowski, Manfred; Cesko, Elvir

    2015-12-01

    Placebo responses have been shown to affect the symptomatology of skin diseases. However, expectation-induced placebo effects on wound healing processes have not been investigated yet. We analysed whether subjects' expectation of receiving an active drug accelerates the healing process of experimentally induced wounds. In 22 healthy men (experimental group, n = 11; control group, n = 11) wounds were induced by ablative laser on both thighs. Using a deceptive paradigm, participants in the experimental group were informed that an innovative 'wound gel' was applied on one of the two wounds, whereas a 'non-active gel' was applied on the wound of the other thigh. In fact, both gels were identical hydrogels without any active components. A control group was informed to receive a non-active gel on both wounds. Progress in wound healing was documented via planimetry on days 1, 4 and 7 after wound induction. From day 9 onwards wound inspections were performed daily accompanied by a change of the dressing and a new application of the gel. No significant differences could be observed with regard to duration or process of wound healing, either by intraindividual or by interindividual comparisons. These data document no expectation-induced placebo effect on the healing process of experimentally induced wounds in healthy volunteers.

  14. Phospholipid composition and kinetics in different endobronchial fractions from healthy volunteers

    PubMed Central

    2014-01-01

    Background Alterations in surfactant phospholipid compositions are a recognized feature of many acute and chronic lung diseases. Investigation of underlying mechanisms requires assessment of surfactant phospholipid molecular composition and kinetics of synthesis and turnover. Such studies have recently become possible in humans due to the development of stable isotope labelling combined with advances in analytical methods in lipidomics. The objectives of this study are to compare phospholipid molecular species composition and phosphatidylcholine synthesis and turnover in surfactant isolated from various endobronchial compartments in healthy adults. Methods Healthy adults (N = 10) were infused with methyl-D9-choline chloride and samples of induced sputum, tracheal wash and small volume bronchoalveolar lavage fluid were obtained subsequently at intervals up to 96 hours. Surfactant phospholipid composition and incorporation of stable isotope into surfactant phosphatidylcholine were determined by electrospray ionisation mass spectrometry. Results While molecular species compositions of phospholipids were similar for all three sample types, dipalmitoylphosphatidylcholine content was highest in lavage, intermediate in tracheal wash and lowest in sputum. Methyl-D9-choline incorporation into surfactant phosphatidylcholine was lower for sputum at 24 hours but reached equilibrium with other sample types by 48 hours. Fractional methyl-D9-dipalmitoylphosphatidylcholine incorporation for all sample types was about 0.5% of the endogenous composition. Lysophosphatidylcholine enrichment was twice than that of phosphatidylcholine. Conclusions Tracheal secretions may be of value as a surrogate to assess bronchoalveolar lavage fluid surfactant molecular composition and metabolism in healthy people. Despite minor differences, the phospholipid molecular composition of induced sputum also showed similarities to that of bronchoalveolar lavage fluid. Detailed analysis of newly

  15. The Relationship between T1 Sagittal Angle and Sagittal Balance: A Retrospective Study of 119 Healthy Volunteers

    PubMed Central

    Li, Ming

    2016-01-01

    T1 sagittal angle has been reported to be used as a parameter for assessing sagittal balance and cervical lordosis. However, no study has been performed to explore the relationship between T1 sagittal angle and sagittal balance, and whether T1 sagittal angle could be used for osteotomy guidelines remains unknown. The aim of our study is to explore the relationship between T1 sagittal angle and sagittal balance, determine the predictors for T1 sagittal angle, and determine whether T1 sagittal angle could be used for osteotomy guidelines to restore sagittal balance. Medical records of healthy volunteers in our outpatient clinic from January 2014 to August 2015 were reviewed, and their standing full-spine lateral radiographs were evaluated. Demographic and radiological parameters were collected and analyzed, including age, gender, T1 sagittal angle, maxTK, maxLL, SS, PT, and PI. Correlation coefficients between T1 sagittal angle and other spinopelvic parameters were determined. In addition, multiple regression analysis was performed to establish predictive radiographic parameters for T1 sagittal angle as the primary contributors. A total of 119 healthy volunteers were recruited in our study with a mean age of 34.7 years. It was found that T1 sagittal angle was correlated with maxTK with very good significance (r = 0.697, P<0.001), maxLL with weak significance (r = 0.206, P = 0.024), SS with weak significance (r = 0.237, P = 0.009), PI with very weak significance (r = 0.189, P = 0.039), SVA with moderate significance (r = 0.445, P<0.001), TPA with weak significance (r = 0.207, P = 0.023), and T1SPI with weak significance (r = 0.309, P = 0.001). The result of multiple regression analysis showed that T1 sagittal angle could be predicted by using the following regression equation: T1 sagittal angle = 0.6 * maxTK—0.2 * maxLL + 8. In the healthy population, T1 sagittal angle could be considered as a useful parameter for sagittal balance; however, it could not be

  16. Effect of CCK-4 on a 35% carbon dioxide challenge in healthy volunteers.

    PubMed

    Pols, H; Griez, E; Bourin, M; Schruers, K

    1999-11-01

    1. The purpose of this study was to determine whether a subthreshold dose of CCK-4 would enhance the vulnerability of healthy subjects to a 35% carbon dioxide challenge. 2. 27 subjects, with no prior or present psychiatric disorder and in good physical condition were challenged with a vital capacity breath of a 35% carbon dioxide mixture, immediately after an intravenous injection of 5 micrograms CCK-4 or placebo, according to a random order double blind crossover design. 3. Subjects reported significantly less panic symptoms upon carbon dioxide after premedication with CCK-4 than after placebo. 4. Both CCK-4 and carbon dioxide may act on the same neuronal pathways, but seem to inhibit rather than potentiate each other effects.

  17. Metabolism of [3H]pentosan polysulfate sodium (PPS) in healthy human volunteers.

    PubMed

    Simon, M; McClanahan, R H; Shah, J F; Repko, T; Modi, N B

    2005-08-01

    Pentosan polysulfate sodium (PPS) is the active ingredient in ELMIRON, a drug approved for the relief of bladder pain associated with interstitial cystitis. The study objective was to characterize the pharmacokinetic and metabolic profiles of PPS following oral dosing of [3H]PPS. As specific assays for PPS do not exist, metabolic profiling was accomplished through multiple fraction collections and radiochromatographic techniques. Two groups of eight healthy female subjects sequentially received a single oral dose of 200 microCi [3H]PPS supplemented with 300 mg unlabelled PPS or 300 microCi [3H]PPS supplemented with 450 mg unlabelled PPS. Most of the administered dose (84%) was excreted in faeces as intact PPS, and a smaller percentage (6%) was excreted in urine. In summary, orally administered PPS was very poorly absorbed, with the majority of the drug being excreted in faeces as intact PPS and in urine as low molecular weight and desulfated PPS.

  18. Histamine intolerance-like symptoms in healthy volunteers after oral provocation with liquid histamine.

    PubMed

    Wöhrl, Stefan; Hemmer, Wolfgang; Focke, Margarete; Rappersberger, Klemens; Jarisch, Reinhart

    2004-01-01

    Histamine in food at non-toxic doses has been proposed to be a major cause of food intolerance causing symptoms like diarrhea, hypotension, headache, pruritus and flush ("histamine intolerance"). Histamine-rich foods such as cheese, sausages, sauerkraut, tuna, tomatoes, and alcoholic beverages may contain histamine up to 500 mg/kg. We conducted a randomized, double-blind, placebo-controlled cross-over study in 10 healthy females (age range 22-36 years, mean 29.1 +/- 5.4) who were hospitalized and challenged on two consecutive days with placebo (peppermint tea) or 75 mg of pure histamine (equaling 124 mg histamine dihydrochloride, dissolved in peppermint tea). Objective parameters (heart rate, blood pressure, skin temperature, peak flow) as well as a total clinical symptom score using a standardized protocol were recorded at baseline, 10, 20, 40, 80 minutes, and 24 hours. The subjects received a histamine-free diet also low in allergen 24 hours before hospitalization and over the whole observation period. Blood samples were drawn at baseline, 10, 20, 40, and 80 minutes, and histamine and the histamine-degrading enzyme diamine oxidase (DAO) were determined. After histamine challenge, 5 of 10 subjects showed no reaction. One individual experienced tachycardia, mild hypotension after 20 minutes, sneezing, itching of the nose, and rhinorrhea after 60 minutes. Four subjects experienced delayed symptoms like diarrhea (4x), flatulence (3x), headache (3x), pruritus (2x) and ocular symptoms (1x) starting 3 to 24 hours after provocation. No subject reacted to placebo. No changes were observed in histamine and DAO levels within the first 80 minutes in non-reactors as well as reactors. There was no difference in challenge with histamine versus challenge with placebo. We conclude that 75 mg of pure liquid oral histamine--a dose found in normal meals--can provoke immediate as well as delayed symptoms in 50% of healthy females without a history of food intolerance. PMID:15603203

  19. Effects of nitric acid gas alone or in combination with ozone on healthy volunteers

    SciTech Connect

    Aris, R.; Christian, D.; Tager, I.; Ngo, L.; Finkbeiner, W.E.; Balmes, J.R. )

    1993-10-01

    Nitric acid (HNO3) is the most prevalent acid air pollutant in the western United States and has the potential to cause adverse respiratory effects through both acidification and oxidation reactions. To study this potential, we measured physiologic (specific airway resistance, SRaw, FEV1, and FVC) and bronchoalveolar lavage (total and differential cell counts, LDH, fibronectin, and total protein) end points in a group of 10 healthy, athletic subjects who were exposed to 500 micrograms/m3 of HNO3 gas or filtered air for 4 h during moderate exercise (ventilatory rate, 40 L/min) and underwent bronchoscopy 18 h later. Under an identical protocol, 10 healthy subjects were exposed to 500 micrograms/m3 of HNO3 gas plus 0.20 ppm ozone (O3) or 0.20 ppm O3 alone to determine if HNO3 might enhance the toxicity of O3. In addition to bronchoalveolar lavage (BAL), we employed the techniques of isolated left mainstem bronchial lavage and bronchial biopsy to determine if proximal airway injury was caused by pollutant exposure and whether there was any correlation with the degree of distal lung injury as assessed by BAL. We found no significant differences in pulmonary function tests or in the cellular or biochemical constituents in either the BAL or the left mainstem lavage fluids between the HNO3 and the air exposures. Similarly, there were no differences in these end points between the HNO3/O3 and the O3 exposures. Furthermore, there were no significant differences in the bronchial biopsy specimens between the HNO3 and air exposures or between the HNO3/O3 and O3 exposures.

  20. A thorough QT study to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine and escitalopram, in healthy volunteers.

    PubMed

    Kim, Anhye; Lim, Kyoung Soo; Lee, Howard; Chung, Hyewon; Yoon, Seo Hyun; Yu, Kyung-Sang; Cho, Joo-Youn; Jang, In-Jin; Chung, Jae-Yong

    2016-07-01

    Prolongation of the QT interval on an ECG is a surrogate marker for predicting the proarrhythmic potential of a drug under development. The aim of this study was to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine immediate release (IR) and escitalopram, in healthy individuals. This was a randomized, open-label, 4×4 Williams crossover study, with four single-dose treatments [placebo, 400 mg moxifloxacin (positive control), 20 mg escitalopram, and 100 mg quetiapine IR], conducted in 40 healthy volunteers. Serial blood samples for pharmacokinetics and ECG were collected. Individually, RR-corrected QTc intervals (QTcI) and placebo-adjusted changes from baseline values of QTcI (ΔΔQTcI) were evaluated. Lower-bound values of the one-sided 95% confidence interval for ΔΔQTcI of moxifloxacin with more than 5 ms confirmed the sensitivity of the assay. The maximum upper bound 95% confidence interval for the ΔΔQTcI of quetiapine IR and escitalopram was 13.7 and 10.5 ms, with mean estimates of 10.2 and 6.9 ms, respectively. Peak effects of moxifloxacin and quetiapine IR on ΔΔQTcI were observed at approximately time to maximum concentration (Tmax), whereas that of escitalopram was observed 3 h after Tmax. The concentration-ΔΔQTcI relationships of quetiapine IR and escitalopram were relatively flat, as compared with that of moxifloxacin. The results demonstrated the validity of trial methodology and that quetiapine IR and escitalopram caused QT prolongation in healthy individuals. In addition, hysteresis of escitalopram-induced QTc prolongation. These results indicate that higher doses of these drugs could lead to greater QT prolongation in a dose-response manner. PMID:26950553

  1. The effect of acute alcohol intoxication on gut wall integrity in healthy male volunteers; a randomized controlled trial.

    PubMed

    de Jong, W J; Cleveringa, A M; Greijdanus, B; Meyer, P; Heineman, E; Hulscher, J B

    2015-02-01

    The aim of the study is to determine the effect of acute alcohol consumption on enterocytes. Chronic alcohol consumption has been known to induce a decrease in gut wall integrity in actively drinking alcoholics and patients with alcohol-induced liver disease. Data on the extent of the damage induced by acute alcohol consumption in healthy human beings is scarce. Studies show that heavy incidental alcohol consumption is a growing problem in modern society. Data on this matter may provide insights into the consequences of this behavior for healthy individuals. In a randomized clinical trial in crossover design, 15 healthy volunteers consumed water one day and alcohol the other. One blood sample was collected pre-consumption, five every hour post-consumption, and one after 24 h. Intestinal fatty acid binding protein (I-FABP) was used as a marker for enterocyte damage. Liver fatty acid binding protein (L-FABP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) were used as markers for hepatocyte damage. Lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) were used as a measure of translocation. Interleukin-6 (IL-6) was used to assess the acute inflammatory response to endotoxemia. Alcohol consumption caused a significant increase in serum I- and L-FABP levels, compared to water consumption. Levels increased directly post-consumption and decreased to normal levels within 4 h. LBP, sCD14, and IL-6 levels were not significantly higher in the alcohol group. Moderate acute alcohol consumption immediately damages the enterocyte but does not seem to cause endotoxemia. PMID:25559494

  2. The effect of acute alcohol intoxication on gut wall integrity in healthy male volunteers; a randomized controlled trial.

    PubMed

    de Jong, W J; Cleveringa, A M; Greijdanus, B; Meyer, P; Heineman, E; Hulscher, J B

    2015-02-01

    The aim of the study is to determine the effect of acute alcohol consumption on enterocytes. Chronic alcohol consumption has been known to induce a decrease in gut wall integrity in actively drinking alcoholics and patients with alcohol-induced liver disease. Data on the extent of the damage induced by acute alcohol consumption in healthy human beings is scarce. Studies show that heavy incidental alcohol consumption is a growing problem in modern society. Data on this matter may provide insights into the consequences of this behavior for healthy individuals. In a randomized clinical trial in crossover design, 15 healthy volunteers consumed water one day and alcohol the other. One blood sample was collected pre-consumption, five every hour post-consumption, and one after 24 h. Intestinal fatty acid binding protein (I-FABP) was used as a marker for enterocyte damage. Liver fatty acid binding protein (L-FABP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) were used as markers for hepatocyte damage. Lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) were used as a measure of translocation. Interleukin-6 (IL-6) was used to assess the acute inflammatory response to endotoxemia. Alcohol consumption caused a significant increase in serum I- and L-FABP levels, compared to water consumption. Levels increased directly post-consumption and decreased to normal levels within 4 h. LBP, sCD14, and IL-6 levels were not significantly higher in the alcohol group. Moderate acute alcohol consumption immediately damages the enterocyte but does not seem to cause endotoxemia.

  3. Safety and pharmacokinetics of multiple doses of aclidinium bromide administered twice daily in healthy volunteers.

    PubMed

    Lasseter, K; Dilzer, S; Jansat, J M; Garcia Gil, E; Caracta, C F; Ortiz, S

    2012-04-01

    Chronic obstructive pulmonary disease (COPD) is characterized by progressive airway obstruction and increased cholinergic tone. The global initiative for chronic obstructive lung disease (GOLD) guidelines recommend long-acting anticholinergics for COPD maintenance treatment. Aclidinium bromide is a novel, long-acting muscarinic antagonist developed for the treatment of COPD. A phase I, randomized, single-blind, multiple-dose clinical trial was conducted to assess the safety and pharmacokinetics (PK) of multiple doses of twice-daily (BID) aclidinium in healthy subjects. Thirty healthy male and female subjects received aclidinium 200 μg, 400 μg, 800 μg, or placebo twice daily for 7 days. Subjects were randomized to 1 of 3 cohorts and 10 subjects in each cohort were randomized (8:2) to either aclidinium or placebo groups. Safety was assessed via adverse events (AEs), laboratory evaluations, vital signs, and ECGs. Plasma samples were obtained at multiple time points throughout the study and analyzed for aclidinium and its inactive acid and alcohol metabolites using a fully validated method of liquid chromatography coupled with tandem mass spectrometry. A total of 9 treatment-emergent AEs were reported (1, placebo; 3, aclidinium 400 μg; 5, aclidinium 800 μg), all of which were mild in severity. No serious AEs were reported. There were no clinically meaningful changes in laboratory parameters or vital signs. PK parameters on Day 7 following BID dosing of aclidinium showed that steady state was achieved for aclidinium and its metabolites. On Days 1 and 7, maximum plasma concentrations (Cmax) of aclidinium were generally observed at the first PK time point (5 min postdose) and rapidly declined, with plasma concentrations generally less than 10% of Cmax by 6 h postdose in all aclidinium groups. Mean effective t(½) after the evening dose on Day 7 ranged from 4.6 to 7.0 h for aclidinium 400 μg and 800 μg, similar to the terminal t(½) observed on Day 1 (4.5-5.9 h

  4. Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers

    PubMed Central

    Volak, Laurie P; Hanley, Michael J; Masse, Gina; Hazarika, Suwagmani; Harmatz, Jerold S; Badmaev, Vladimir; Majeed, Muhammed; Greenblatt, David J; Court, Michael H

    2013-01-01

    Aims Turmeric extract derived curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) are currently being evaluated for the treatment of cancer and Alzheimer's dementia. Previous in vitro studies indicate that curcuminoids and piperine (a black pepper derivative that enhances curcuminoid bioavailability) could inhibit human CYP3A, CYP2C9, UGT and SULT dependent drug metabolism. The aim of this study was to determine whether a commercially available curcuminoid/piperine extract alters the pharmacokinetic disposition of probe drugs for these enzymes in human volunteers. Methods A randomized placebo-controlled six way crossover study was conducted in eight healthy volunteers. A standardized curcuminoid/piperine preparation (4 g curcuminoids plus 24 mg piperine) or matched placebo was given orally four times over 2 days before oral administration of midazolam (CYP3A probe), flurbiprofen (CYP2C9 probe) or paracetamol (acetaminophen) (dual UGT and SULT probe). Plasma and urine concentrations of drugs, metabolites and herbals were measured by HPLC. Subject sedation and electroencephalograph effects were also measured following midazolam dosing. Results Compared with placebo, the curcuminoid/piperine treatment produced no meaningful changes in plasma Cmax, AUC, clearance, elimination half-life or metabolite levels of midazolam, flurbiprofen or paracetamol (α = 0.05, paired t-tests). There was also no effect of curcuminoid/piperine treatment on the pharmacodynamics of midazolam. Although curcuminoid and piperine concentrations were readily measured in plasma following glucuronidase/sulfatase treatment, unconjugated concentrations were consistently below the assay thresholds (0.05–0.08 μm and 0.6 μm, respectively). Conclusion The results indicate that short term use of this piperine-enhanced curcuminoid preparation is unlikely to result in a clinically significant interaction involving CYP3A, CYP2C9 or the paracetamol conjugation enzymes. PMID:22725836

  5. Development of tolerance after repeated administration of a selective muscarinic M1 antagonist biperiden in healthy human volunteers.

    PubMed

    Salin-Pascual, R J; Granados-Fuentes, D; Galicia-Polo, L; Nieves, E; Gillin, J C

    1993-02-01

    The muscarinic antagonist biperiden produces a dose-dependent inhibition of (REM) sleep on acute administration. The present study addressed the possibility of pharmacological tolerance after repeated biperiden administration. Six healthy volunteers were studied under sleep laboratory conditions in the following situations: one acclimatization, night, two baseline (that were averaged), 4 nights of biperiden administration, and 4 nights of placebo recovery administration. Six milligrams of biperiden and placebo were administered in identical capsules. Volunteers and technicians were blind to the order of the administration of the capsules. REM sleep time was reduced during the first and the second night, but was not significantly different in comparison with baseline by the third night. During placebo recovery nights, REM sleep time was not different from baseline. REM sleep latency was increased during the first and second nights of biperiden administration, but tolerance to this effect was observed by the third night. On placebo nights a dramatic shortening of REM latency was observed. The present findings support the hypothesis that anticholinergic drugs, even a selective M1 antagonist such as biperiden, induce tolerance soon after administration. A similar effect has been reported with scopolamine, a nonselective muscarinic antagonist, but the main difference is that biperiden withdrawal was not followed by an REM sleep rebound. The observed effect on REM sleep latency during placebo administration may be related to a supersensitivity to muscarinic M-1 receptors that trigger the first REM sleep period. Because short REM latency has been the main finding in the sleep of depressed patients, some implications of the present findings are discussed.

  6. Assessing efficacy of non-opioid analgesics in experimental pain models in healthy volunteers: an updated review

    PubMed Central

    Staahl, Camilla; Olesen, Anne Estrup; Andresen, Trine; Arendt-Nielsen, Lars; Drewes, Asbjørn Mohr

    2009-01-01

    AIM Experimental pain models may help to evaluate the mechanisms of analgesics and target the clinical indications for their use. This review, the second in a series of two, addresses how the efficacy of non-opioid analgesics have been assessed in human volunteers using experimental pain models. METHODS A literature search was completed for randomized controlled studies that included human experimental pain models, healthy volunteers and non-opioid analgesics. RESULTS Nonsteroidal anti-inflammatory drugs worked against various types of acute pain as well as in hyperalgesia. Analgesia from paracetamol was difficult to detect in experimental pain and the pain needed to be assessed with very sensitive methods like evoked brain potentials. The N-methyl-D-aspartate antagonists exemplified by ketamine generally needed strong, long-lasting or repeated pain in the skin for detectable analgesia, whereas pain in muscle and viscera generally was more easily attenuated. Gabapentin worked well in several models, particularly those inducing hyperalgesia, whereas lamotrigine was weak in modulation of experimental pain. Imipramine attenuated pain in most experimental models, whereas amitriptyline had weaker effects. Delta-9-tetrahydrocannabinol attenuated pain in only a few models. CONCLUSIONS Pain induction and assessment are very important for the sensitivity of the pain models. Generally, experimental pain models need to be designed with careful consideration of the pharmacological mechanisms and pharmacokinetics of analgesics. The drawback with the different study designs is also discussed. This knowledge can aid the decisions that need to be taken when designing experimental pain studies for compounds entering Phase I and II trials. PMID:19740390

  7. Modafinil combined with cognitive training is associated with improved learning in healthy volunteers--a randomised controlled trial.

    PubMed

    Gilleen, J; Michalopoulou, P G; Reichenberg, A; Drake, R; Wykes, T; Lewis, S W; Kapur, S

    2014-04-01

    Improving cognition in people with neuropsychiatric disorders remains a major clinical target. By themselves pharmacological and non-pharmacological approaches have shown only modest effects in improving cognition. In the present study we tested a recently-proposed methodology to combine CT with a 'cognitive-enhancing' drug to improve cognitive test scores and expanded on previous approaches by delivering combination drug and CT, over a long intervention of repeated sessions, and used multiple tasks to reveal the cognitive processes being enhanced. We also aimed to determine whether gains from this combination approach generalised to untrained tests. In this proof of principle randomised-controlled trial thirty-three healthy volunteers were randomised to receive either modafinil or placebo combined with daily cognitive training over two weeks. Volunteers were trained on tasks of new-language learning, working memory and verbal learning following 200 mg modafinil or placebo for ten days. Improvements in trained and untrained tasks were measured. Rate of new-language learning was significantly enhanced with modafinil, and effects were greatest over the first five sessions. Modafinil improved within-day learning rather than between-day retention. No enhancement of gains with modafinil was observed in working memory nor rate of verbal learning. Gains in all tasks were retained post drug-administration, but transfer effects to broad cognitive abilities were not seen. This study shows that combining CT with modafinil specifically elevates learning over early training sessions compared to CT with placebo and provides a proof of principle experimental paradigm for pharmacological enhancement of cognitive remediation.

  8. Acute NK₁ receptor antagonist administration affects reward incentive anticipation processing in healthy volunteers.

    PubMed

    Saji, Kanako; Ikeda, Yumiko; Kim, Woochan; Shingai, Yoshitoshi; Tateno, Amane; Takahashi, Hidehiko; Okubo, Yoshiro; Fukayama, Haruhisa; Suzuki, Hidenori

    2013-08-01

    The primary brain structures of reward processing are mainly situated in the mid-brain dopamine system. The nucleus accumbens (NAc) receives dopaminergic projections from the ventral tegmental area and works as a key brain region for the positive incentive value of rewards. Because neurokinin-1 (NK₁) receptor, the cognate receptor for substance P (SP), is highly expressed in the NAc, we hypothesized that the SP/NK₁ receptor system might play a role in positive reward processing in the NAc in humans. Therefore, we conducted a functional MRI (fMRI) study to assess the effects of an NK₁ receptor antagonist on human reward processing through a monetary incentive delay task that is known to elicit robust activation in the NAc especially during gain anticipation. Eighteen healthy adults participated in two series of an fMRI study, taking either a placebo or the NK₁ receptor antagonist aprepitant. Behavioural measurements revealed that there was no significant difference in reaction time, hit rate, or self-reported effort for incentive cues between the placebo and aprepitant treatments. fMRI showed significant decrease in blood oxygenation-level-dependent signals in the NAc during gain anticipation with the aprepitant treatment compared to the placebo treatment. These results suggest that SP/NK₁ receptor system is involved in processing of positive incentive anticipation and plays a role in accentuating positive valence in association with the primary dopaminergic pathways in the reward circuit.

  9. Modafinil affects mood, but not cognitive function, in healthy young volunteers.

    PubMed

    Randall, Delia C; Shneerson, John M; Plaha, Komal K; File, Sandra E

    2003-04-01

    Modafinil is a selective wakefulness-promoting agent with beneficial effects in narcolepsy and conditions of sleep deprivation. In a double-blind study we examined its effects in 30 healthy, non sleep-deprived students (19 men and 11 women, aged 19-23 years), who were randomly allocated to placebo, 100 or 200 mg modafinil and 3 h later completed 100 mm visual analogue scales relating to mood and bodily symptoms, before and after an extensive battery of cognitive tests (pen and paper and CANTAB). There were no significant differences between the three treatment groups on any of the cognitive tests used in this study. There was a significant post-treatment change in the factor measuring 'somatic anxiety' and in individual ratings of 'shaking', 'palpitations', 'dizziness', 'restlessness', 'muscular tension', 'physical tiredness' and 'irritability', which was mainly due to significantly higher ratings of somatic anxiety in the 100 mg group compared with the other two groups. Further changes in mood were revealed after the stress of cognitive testing, with the 100 mg group showing greater increases in the 'psychological anxiety' and the 'aggressive mood' factors (as measured from the Bond and Lader scales). PMID:12672167

  10. [Central effects of five beta-adrenergic receptor blockers in healthy volunteers: a quantitative EEG study].

    PubMed

    Sabot, C; Pechadre, J C; Beudin, P; Lauxerois, M; Trolese, J F; Kantelip, J P; Ducher, J L; Gibert, J

    1989-03-01

    The effects of five beta blockers on the central nervous system of healthy subjects was studied by computerized EEG analysis. All subjects underwent continuous recording with a Holter magnetic type recorder during the experimental period. For 10 consecutive days, five groups of subjects received alternately placebo and the beta blockers acebutolol 600 mg, carteolol 20 mg, metoprolol 200 mg, pindolol 30 mg and sotalol 320 mg. EEG recordings (C4/P4, P4/02 and C3/P3, P3/01) lasting 5 min were made between 8.30 and 9.30 a.m. Subjects were at rest with eyes closed and there was no vigilance control. The signal was recorded on a magnetic tape recorder and then processed by Nicolet MED 80 system. Comparisons of absolute and relative powers and of average frequencies were then made between the different sequences and groups. The possible correlations between the changes observed in the power spectrum and the clinical, pharmacological and pharmacokinetic specific properties of each beta blocker are discussed.

  11. Effects of amlodipine on the oral bioavailability of cephalexin and cefuroxime axetil in healthy volunteers.

    PubMed

    Ding, Yi; Liu, WenXing; Jia, YanYan; Lu, ChengTao; Jin, Xin; Yang, Jing; Zhu, YanRong; Yang, Lin; Song, Ying; Ding, LiKun; Wen, AiDong

    2013-01-01

    In this study, the authors compared the effects of amlodipine (AML) on the bioavailability of cephalexin (LEX) and cefuroxime axetil (CXM). Twenty-four healthy men were randomized to 4 treatments according to a crossover design with a 14-day washout. After an overnight fast, they were administered orally LEX 500 mg alone, LEX 500 mg 2 hours after oral administration of AML 5 mg, CXM 500 mg alone, and CXM 500 mg 2 hours after oral administration of AML 5 mg. All participants completed the whole study without side effects being observed. Pharmacokinetic data were analyzed by noncompartmental modeling with WinNonlin software. The geometric mean (GM) ratios were 1.38 (90% confidence interval [CI], 1.32-1.45) for the area under the concentration-time curve (AUC) for LEX and 1.27 (1.18-1.36) for the maximum concentration of drug in serum (C(max)) for LEX followed by AML versus alone. In contrast, no significant differences were found in the pharmacokinetic parameters of CXM between treatments (P < .05). They authors conclude that AML possesses an enhancement effect in β-lactam antibiotic bioavailability (in this case, LEX), and this interaction may be specific to the peptidomimetic β-lactam antibiotics.

  12. Inter- and intrasubject variabilities in the pharmacokinetics of rufloxacin after single oral administration to healthy volunteers.

    PubMed Central

    Imbimbo, B P; Broccali, G; Cesana, M; Crema, F; Attardo-Parrinello, G

    1991-01-01

    Rufloxacin is a new long-acting, once-daily quinolone antibacterial agent. We evaluated inter- and intrasubject variations in pharmacokinetics of rufloxacin following oral administration of 400 mg (two capsules) under controlled conditions, at an interval of 2 weeks (periods I and II), to 12 healthy male subjects. Plasma and urine samples were collected up to 48 h after drug administration. Plasma drug levels determined by bioassay were higher than those measured by high-performance liquid chromatography, indicating that one or more active metabolites were formed. Individual high-performance liquid chromatography plasma rufloxacin concentrations were fitted with a one-compartment open model with first-order input. There were considerable variations in the plasma concentration-time profiles among subjects; for example, the elimination half-life in plasma varied from 14.6 to 95.5 h. However, pharmacokinetic parameters calculated for the two periods did not differ significantly. These results suggest that the intrasubject variation in the pharmacokinetics of rufloxacin is usually small in spite of the considerable intersubject variation. PMID:2024974

  13. Detection of novel Chlamydiae and Legionellales from human nasal samples of healthy volunteers.

    PubMed

    Corsaro, Daniele; Venditti, Danielle

    2015-07-01

    Chlamydiae are intracellular bacterial parasites of eukaryotes, ranging from amoebae to humans. They comprise many novel members and are investigated as emerging pathogens. Environmental studies highlighted similarities between the ecologies of chlamydiae and legionellae, both groups being important agents of respiratory infections. Herein, we analyzed nasal samples from healthy persons, searching for the presence of amoebae, chlamydiae and legionellae. From a total of 25 samples, we recovered by PCR eight samples positive to chlamydiae and six samples positive to legionellae. Among these samples, four were positive to both organisms. The sequencing of 16S rDNAs allowed to identify (i) among Chlamydiae: Parachlamydia acanthamoebae, Chlamydophila psittaci, Chlamydophila felis, and members of Rhabdochlamydiaceae, Simkaniaceae and E6 lineage and (ii) among Legionellaceae: Legionella longbeachae, Legionella bozemanii and Legionella impletisoli. Unexpectedly, we also recovered Diplorickettsia sp. Amoebae collected from nasal mucosae, Acanthamoeba and Vermamoeba, were endosymbiont-free, and chlamydiae revealed refractory to amoeba coculture. This study shows common exposure to chlamydiae and legionellae and suggests open air activities like gardening as a probable additional source of infection.

  14. Oral T4-like phage cocktail application to healthy adult volunteers from Bangladesh

    SciTech Connect

    Sarker, Shafiqul Alam; McCallin, Shawna; Barretto, Caroline; Berger, Bernard; Pittet, Anne-Cecile; Sultana, Shamima; Krause, Lutz; Huq, Sayeda; Bibiloni, Rodrigo; Bruttin, Anne; Reuteler, Gloria; Bruessow, Harald

    2012-12-20

    The genomic diversity of 99 T4-like coliphages was investigated by sequencing an equimolar mixture with Illumina technology and screening them against different databases for horizontal gene transfer and undesired genes. A 9-phage cocktail was given to 15 healthy adults from Bangladesh at a dose of 3 Multiplication-Sign 10{sup 9} and 3 Multiplication-Sign 10{sup 7} plaque-forming units and placebo respectively. Phages were detected in 64% of the stool samples when subjects were treated with higher titer phage, compared to 30% and 28% with lower-titer phage and placebo, respectively. No Escherichia coli was present in initial stool samples, and no amplification of phage was observed. One percent of the administered oral phage was recovered from the feces. No adverse events were observed by self-report, clinical examination, or from laboratory tests for liver, kidney, and hematology function. No impact of oral phage was seen on the fecal microbiota composition with respect to bacterial 16S rRNA from stool.

  15. Detection of novel Chlamydiae and Legionellales from human nasal samples of healthy volunteers.

    PubMed

    Corsaro, Daniele; Venditti, Danielle

    2015-07-01

    Chlamydiae are intracellular bacterial parasites of eukaryotes, ranging from amoebae to humans. They comprise many novel members and are investigated as emerging pathogens. Environmental studies highlighted similarities between the ecologies of chlamydiae and legionellae, both groups being important agents of respiratory infections. Herein, we analyzed nasal samples from healthy persons, searching for the presence of amoebae, chlamydiae and legionellae. From a total of 25 samples, we recovered by PCR eight samples positive to chlamydiae and six samples positive to legionellae. Among these samples, four were positive to both organisms. The sequencing of 16S rDNAs allowed to identify (i) among Chlamydiae: Parachlamydia acanthamoebae, Chlamydophila psittaci, Chlamydophila felis, and members of Rhabdochlamydiaceae, Simkaniaceae and E6 lineage and (ii) among Legionellaceae: Legionella longbeachae, Legionella bozemanii and Legionella impletisoli. Unexpectedly, we also recovered Diplorickettsia sp. Amoebae collected from nasal mucosae, Acanthamoeba and Vermamoeba, were endosymbiont-free, and chlamydiae revealed refractory to amoeba coculture. This study shows common exposure to chlamydiae and legionellae and suggests open air activities like gardening as a probable additional source of infection. PMID:25697709

  16. Pomegranate extract induces ellagitannin metabolite formation and changes stool microbiota in healthy volunteers.

    PubMed

    Li, Zhaoping; Henning, Susanne M; Lee, Ru-Po; Lu, Qing-Yi; Summanen, Paula H; Thames, Gail; Corbett, Karen; Downes, Julia; Tseng, Chi-Hong; Finegold, Sydney M; Heber, David

    2015-08-01

    The health benefits of pomegranate (POM) consumption are attributed to ellagitannins and their metabolites, formed and absorbed in the intestine by the microbiota. In this study twenty healthy participants consumed 1000 mg of POM extract daily for four weeks. Based on urinary and fecal content of the POM metabolite urolithin A (UA), we observed three distinct groups: (1) individuals with no baseline UA presence but induction of UA formation by POM extract consumption (n = 9); (2) baseline UA formation which was enhanced by POM extract consumption (N = 5) and (3) no baseline UA production, which was not inducible (N = 6). Compared to baseline the phylum Actinobacteria was increased and Firmicutes decreased significantly in individuals forming UA (producers). Verrucomicrobia (Akkermansia muciniphila) was 33 and 47-fold higher in stool samples of UA producers compared to non-producers at baseline and after 4 weeks, respectively. In UA producers, the genera Butyrivibrio, Enterobacter, Escherichia, Lactobacillus, Prevotella, Serratia and Veillonella were increased and Collinsella decreased significantly at week 4 compared to baseline. The consumption of pomegranate resulted in the formation of its metabolites in some but not all participants. POM extract consumption may induce health benefits secondary to changes in the microbiota.

  17. Cognitive effects of methylphenidate in healthy volunteers: a review of single dose studies.

    PubMed

    Linssen, A M W; Sambeth, A; Vuurman, E F P M; Riedel, W J

    2014-06-01

    Methylphenidate (MPH), a stimulant drug with dopamine and noradrenaline reuptake inhibition properties, is mainly prescribed in attention deficit hyperactivity disorder, is increasingly used by the general population, intending to enhance their cognitive function. In this literature review, we aim to answer whether this is effective. We present a novel way to determine the extent to which MPH enhances cognitive performance in a certain domain. Namely, we quantify this by a percentage that reflects the number of studies showing performance enhancing effects of MPH. To evaluate whether the dose-response relationship follows an inverted-U-shaped curve, MPH effects on cognition are also quantified for low, medium and high doses, respectively. The studies reviewed here show that single doses of MPH improve cognitive performance in the healthy population in the domains of working memory (65% of included studies) and speed of processing (48%), and to a lesser extent may also improve verbal learning and memory (31%), attention and vigilance (29%) and reasoning and problem solving (18%), but does not have an effect on visual learning and memory. MPH effects are dose-dependent and the dose-response relationship differs between cognitive domains. MPH use is associated with side effects and other adverse consequences, such as potential abuse. Future studies should focus on MPH specifically to adequately asses its benefits in relation to the risks specific to this drug.

  18. Pomegranate extract induces ellagitannin metabolite formation and changes stool microbiota in healthy volunteers.

    PubMed

    Li, Zhaoping; Henning, Susanne M; Lee, Ru-Po; Lu, Qing-Yi; Summanen, Paula H; Thames, Gail; Corbett, Karen; Downes, Julia; Tseng, Chi-Hong; Finegold, Sydney M; Heber, David

    2015-08-01

    The health benefits of pomegranate (POM) consumption are attributed to ellagitannins and their metabolites, formed and absorbed in the intestine by the microbiota. In this study twenty healthy participants consumed 1000 mg of POM extract daily for four weeks. Based on urinary and fecal content of the POM metabolite urolithin A (UA), we observed three distinct groups: (1) individuals with no baseline UA presence but induction of UA formation by POM extract consumption (n = 9); (2) baseline UA formation which was enhanced by POM extract consumption (N = 5) and (3) no baseline UA production, which was not inducible (N = 6). Compared to baseline the phylum Actinobacteria was increased and Firmicutes decreased significantly in individuals forming UA (producers). Verrucomicrobia (Akkermansia muciniphila) was 33 and 47-fold higher in stool samples of UA producers compared to non-producers at baseline and after 4 weeks, respectively. In UA producers, the genera Butyrivibrio, Enterobacter, Escherichia, Lactobacillus, Prevotella, Serratia and Veillonella were increased and Collinsella decreased significantly at week 4 compared to baseline. The consumption of pomegranate resulted in the formation of its metabolites in some but not all participants. POM extract consumption may induce health benefits secondary to changes in the microbiota. PMID:26189645

  19. Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers

    PubMed Central

    Johnson, Matthew W.; Sewell, R. Andrew; Griffiths, Roland R.

    2011-01-01

    Background Psilocybin is a well-characterized classic hallucinogen (psychedelic) with a long history of religious use by indigenous cultures, and nonmedical use in modern societies. Although psilocybin is structurally related to migraine medications, and case studies suggest that psilocybin may be efficacious in treatment of cluster headache, little is known about the relationship between psilocybin and headache. Methods This double-blind study examined a broad range of psilocybin doses (0, 5, 10, 20, and 30 mg/70 kg) on headache in 18 healthy participants. Results Psilocybin frequently caused headache, the incidence, duration, and severity of which increased in a dose-dependent manner. All headaches had delayed onset, were transient, and lasted no more than a day after psilocybin administration. Conclusions Possible mechanisms for these observations are discussed, and include induction of delayed headache through nitric oxide release. These data suggest that headache is an adverse event to be expected with the nonmedical use of psilocybin-containing mushrooms as well as the administration of psilocybin in human research. Headaches were neither severe nor disabling, and should not present a barrier to future psilocybin research. PMID:22129843

  20. Reduced fear-recognition sensitivity following acute buprenorphine administration in healthy volunteers.

    PubMed

    Ipser, Jonathan C; Terburg, David; Syal, Supriya; Phillips, Nicole; Solms, Mark; Panksepp, Jaak; Malcolm-Smith, Susan; Thomas, Kevin; Stein, Dan J; van Honk, Jack

    2013-01-01

    In rodents, the endogenous opioid system has been implicated in emotion regulation, and in the reduction of fear in particular. In humans, while there is evidence that the opioid antagonist naloxone acutely enhances the acquisition of conditioned fear, there are no corresponding data on the effect of opioid agonists in moderating responses to fear. We investigated whether a single 0.2mg administration of the mu-opioid agonist buprenorphine would decrease fear sensitivity with an emotion-recognition paradigm. Healthy human subjects participated in a randomized placebo-controlled within-subject design, in which they performed a dynamic emotion recognition task 120min after administration of buprenorphine and placebo. In the recognition task, basic emotional expressions were morphed between their full expression and neutral in 2% steps, and presented as dynamic video-clips with final frames of different emotional intensity for each trial, which allows for a fine-grained measurement of emotion sensitivity. Additionally, visual analog scales were used to investigate acute effects of buprenorphine on mood. Compared to placebo, buprenorphine resulted in a significant reduction in the sensitivity for recognizing fearful facial expressions exclusively. Our data demonstrate, for the first time in humans, that acute up-regulation of the opioid system reduces fear recognition sensitivity. Moreover, the absence of an effect of buprenorphine on mood provides evidence of a direct influence of opioids upon the core fear system in the human brain. PMID:22651957

  1. Free and protein-bound glutamine have identical splanchnic extraction in healthy human volunteers.

    PubMed

    Boza, J J; Dangin, M; Moënnoz, D; Montigon, F; Vuichoud, J; Jarret, A; Pouteau, E; Gremaud, G; Oguey-Araymon, S; Courtois, D; Woupeyi, A; Finot, P A; Ballèvre, O

    2001-07-01

    The objectives of the present study were to determine the splanchnic extraction of glutamine after ingestion of glutamine-rich protein ((15)N-labeled oat proteins) and to compare it with that of free glutamine and to determine de novo glutamine synthesis before and after glutamine consumption. Eight healthy adults were infused intravenously in the postabsorptive state with L-[1-(13)C]glutamine (3 micromol x kg(-1) x h(-1)) and L-[1-(13)C]lysine (1.5 micromol x kg(-1) x h(-1)) for 8 h. Four hours after the beginning of the infusion, subjects consumed (every 20 min) a liquid formula providing either 2.5 g of protein from (15)N-labeled oat proteins or a mixture of free amino acids that mimicked the oat-amino acid profile and contained L-[2,5-(15)N(2)]glutamine and L-[2-(15)N]lysine. Splanchnic extraction of glutamine reached 62.5 +/- 5.0% and 66.7 +/- 3.9% after administration of (15)N-labeled oat proteins and the mixture of free amino acids, respectively. Lysine splanchnic extraction was also not different (40.9 +/- 11.9% and 34.9 +/- 10.6% for (15)N-labeled oat proteins and free amino acids, respectively). The main conclusion of the present study is that glutamine is equally bioavailable when given enterally as a free amino acid and when protein bound. Therefore, and taking into consideration the drawbacks of free glutamine supplementation of ready-to-use formulas for enteral nutrition, protein sources naturally rich in this amino acid are the best option for providing stable glutamine.

  2. Urinary thrombomodulin and catecholamine levels are interrelated in healthy volunteers immersed in cold and warm water.

    PubMed

    Pakanen, Lasse; Pääkkönen, Tiina; Ikäheimo, Tiina M; Rintamäki, Hannu; Leppäluoto, Juhani; Kaija, Helena; Kortelainen, Marja-Leena; Rautio, Arja; Porvari, Katja

    2016-01-01

    Severe hypothermia has been shown to influence the levels of catecholamines and thrombomodulin, an endothelial protein essentially involved in the regulation of haemostasis and inflammation. A link between thrombomodulin and catecholamines during cold exposure has also been previously suggested. The aim of this study was to assess the influence of short-term cold exposure without hypothermia on catecholamines and the circulating and urinary thrombomodulin levels. Seven healthy male subjects were immersed in cold water (+10°C) for 10 minutes followed by a 20-minute immersion in +28°C water. Warm water immersion was performed separately for each subject (+30°C for 30 minutes). Thrombomodulin and catecholamine concentrations were measured from pre- and post-immersion (up to 23 hours) samples. In urine, the thrombomodulin level correlated strongly with adrenaline (ρ = 0.806) and noradrenaline (ρ = 0.760) levels. There were no significant differences in thrombomodulin levels between immersion temperatures. Post-immersion urinary thrombomodulin levels were significantly lower than the pre-immersion level at both immersion temperatures. Median concentrations of plasma noradrenaline and urinary adrenaline were higher after exposure to +10°C than to +30°C. Thus, further evidence of the association between thrombomodulin and catecholamines was gained in a physiologically relevant setting in humans. Additionally, it is evident that a short-term cold exposure was not able to elicit changes in the thrombomodulin levels in a follow-up period of up to 23 hours. These findings provide further understanding of the physiological responses to cold during immersion, and of the potential influence of stress on haemostatic and inflammatory responses. PMID:27227082

  3. Evaluation of the pharmacokinetic and pharmacodynamic drug interactions between cilnidipine and valsartan, in healthy volunteers

    PubMed Central

    Lee, Jieon; Lee, Howard; Jang, Kyungho; Lim, Kyoung Soo; Shin, Dongseong; Yu, Kyung-Sang

    2014-01-01

    Purpose Although cilnidipine and valsartan are widely coadministered to patients with hypertension, their drug–drug interaction potential has not been investigated. This study compared the pharmacokinetic (PK), pharmacodynamic (PD), and tolerability profiles of cilnidipine and valsartan, both alone and in combination, in healthy male subjects. Patients and methods Fifty-four subjects, enrolled into an open-label, single-dose, three-treatment, three-period crossover study, randomly received cilnidipine (10 mg), valsartan (160 mg), or both according to one of six sequences. Blood samples were collected at baseline and up to 24 hours after drug administration in each period. Plasma concentrations of cilnidipine and valsartan were determined by liquid chromatography with tandem mass spectrometry. Maximum plasma concentration (Cmax) and area under the concentration-time curve from 0 to the last measurable time (AUClast) were estimated using a noncompartmental method. Tolerability was evaluated by assessing adverse events (AEs), vital signs, electrocardiograms, and clinical laboratory tests. Blood pressure was also measured for PD assessment. Results A total of 51 subjects completed the study. The PK profile of cilnidipine was not significantly affected by coadministered valsartan; the geometric mean ratio and 90% confidence interval (90% CI) of AUClast for cilnidipine with and without valsartan was 1.04 (0.98–1.10). Likewise, cilnidipine did not affect the PK of valsartan; the geometric mean ratio (90% CI) of AUClast for valsartan with and without cilnidipine was 0.94 (0.83–1.07). Coadministration of cilnidipine and valsartan reduced blood pressure in an additive way. No serious AEs were reported, and both cilnidipine and valsartan were well tolerated. Conclusion Coadministered cilnidipine and valsartan do not cause a significant PK or PD interaction, and they are well tolerated. PMID:25336921

  4. Lactobacillus isolates from healthy volunteers exert immunomodulatory effects on activated peripheral blood mononuclear cells

    PubMed Central

    Sun, Keyi; Xie, Chao; Xu, Donghua; Yang, Xiaofan; Tang, James; Ji, Xiaohui

    2013-01-01

    As probiotics in the gut, Lactobacilli are believed to play important roles in the development and maintenance of both the mucosal and systemic immune system of the host. This study was aimed to investigate the immuno-modulatory function of candiate lactobacilli on T cells. Lactobacilli were isolated from healthy human feces and the microbiological characteristics were identified by API 50 CHL and randomly amplified polymorphic DNA (RAPD) assays. Anti-CD3 antibody activated peripheral blood mononuclear cells (PBMCs) were treated by viable, heat-killed lactobacilli and genomic DNA of lactobacilli, and cytokine profiles were tested by ELISA. Isolated lactobacilli C44 and C48 were identified as L. acidophilus and L. paracacei, which have properties of acid and bile tolerance and inhibitor effects on pathogens. Viable and heat-killed C44 and C48 induced low levels of proinflammatory cytokines (TNF-α, IL-6 and IL-8) and high levels of IFN-γ and IL-12p70 in PBMCs. In anti-CD3 antibody activated PBMCs, viable and heat-killed C44 increased Th2 cytokine levels (IL-5, IL-6 and IL-10), and simultaneously enhanced Th1 responses by inducing IFN-γ and IL-12p70 production. Different from that of lactabacillus strains, their genomic DNA induced low levels of IL-12p70, IFN-γ and proinflammatory cytokines in PBMCs with or without anti-CD3 antibody activation. These results provided in vitro evidence that the genomic DNA of strains of C44 and C48, especially C44, induced weaker inflammation, and may be potentially applied for treating allergic diseases. PMID:23554802

  5. A Randomized Phase 1 Dose Escalation Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Trabodenoson in Healthy Adult Volunteers

    PubMed Central

    Laties, Alan; Rich, Cadmus C.; Stoltz, Randall; Humbert, Vernon; Brickman, Chaim; McVicar, William

    2016-01-01

    Abstract Purpose: To investigate the safety, tolerability, and pharmacokinetics of trabodenoson, a highly selective adenosine mimetic targeting the adenosine A1 receptor. Methods: In Part 1, 60 healthy adult volunteers were randomized to 14 days of twice-daily topical monocular application of placebo or trabodenoson (200, 400, 800, 1,600, 2,400, or 3,200 μg). In Part 2, 10 subjects were randomized to placebo or 8 escalating doses of bilateral trabodenoson (total daily doses: 1,800–6,400 μg). Results: The incidence of treatment-related adverse events in Part 1 was similar in the trabodenoson (27.8%) and placebo (25.0%) groups. Most were mild in intensity. The most common adverse events (AEs) for trabodenoson and placebo were headache (25.0% vs. 33%, respectively) and eye pain (11.1% vs. 4.2%, respectively). Ocular AEs were infrequent (16.7% and 17.9%, respectively), were self-limited, lasted <24 h, and were typically mild in intensity. The most common ocular AE was eye pain (9.5% and 3.6%, respectively), with a single observation of ocular hyperemia (200 μg trabodenoson). Trabodenoson was rapidly absorbed [median time to maximum concentration (tmax): ∼0.08 to 0.27 h] and eliminated (t½: 0.48–2.0 h), with no evidence of drug accumulation. Systemic exposure to topical trabodenoson was dose related but not dose proportional, with a plateau effect at doses ≥2,400 mg per eye. No clinically significant treatment-related systemic AEs were observed, and increasing systemic exposure had no effect on heart rate or blood pressure. Conclusions: Ocular doses of trabodenoson up to 3,200 μg per eye were safe and well tolerated in the eye and resulted in no detectable systemic effects in healthy adult volunteers. PMID:27046445

  6. Effect of a high dose of simvastatin on muscle mitochondrial metabolism and calcium signaling in healthy volunteers

    SciTech Connect

    Galtier, F.; Mura, T.; Raynaud de Mauverger, E.; Chevassus, H.; Farret, A.; Gagnol, J.-P.; Costa, F.; Dupuy, A.; and others

    2012-09-15

    Statin use may be limited by muscle side effects. Although incompletely understood to date, their pathophysiology may involve oxidative stress and impairments of mitochondrial function and of muscle Ca{sup 2+} homeostasis. In order to simultaneously assess these mechanisms, 24 male healthy volunteers were randomized to receive either simvastatin for 80 mg daily or placebo for 8 weeks. Blood and urine samples and a stress test were performed at baseline and at follow-up, and mitochondrial respiration and Ca{sup 2+} spark properties were evaluated on a muscle biopsy 4 days before the second stress test. Simvastatin-treated subjects were separated according to their median creatine kinase (CK) increase. Simvastatin treatment induced a significant elevation of aspartate amino transferase (3.38 ± 5.68 vs − 1.15 ± 4.32 UI/L, P < 0.001) and CK (− 24.3 ± 99.1 ± 189.3vs 48.3 UI/L, P = 0.01) and a trend to an elevation of isoprostanes (193 ± 408 vs12 ± 53 pmol/mmol creatinine, P = 0.09) with no global change in mitochondrial respiration, lactate/pyruvate ratio or Ca{sup 2+} sparks. However, among statin-treated subjects, those with the highest CK increase displayed a significantly lower Vmax rotenone succinate and an increase in Ca{sup 2+} spark amplitude vs both subjects with the lowest CK increase and placebo-treated subjects. Moreover, Ca{sup 2+} spark amplitude was positively correlated with treatment-induced CK increase in the whole group (r = 0.71, P = 0.0045). In conclusion, this study further supports that statin induced muscular toxicity may be related to alterations in mitochondrial respiration and muscle calcium homeostasis independently of underlying disease or concomitant medication. -- Highlights: ► Statin use may be limited by side effects, particularly myopathy. ► Statins might impair mitochondrial function and muscle Ca2+ signaling in muscle. ► This was tested among healthy volunteers receiving simvastatin 80 mg daily for 8 weeks. ► CK

  7. Metabolic disposition of 14C-bromfenac in healthy male volunteers.

    PubMed

    Osman, M; Chandrasekaran, A; Chan, K; Scatina, J; Ermer, J; Cevallos, W; Sisenwine, S F

    1998-08-01

    The metabolic disposition of 14C-bromfenac, an orally active, potent, nonsteroidal, nonnarcotic, analgesic agent was investigated in six healthy male subjects after a single oral 50-mg dose. The absorption of radioactivity was rapid, producing a mean maximum plasma concentration (Cmax) of 4.9 +/- 1.8 microg x equiv/mL, which was reached 1.0 +/- 0.5 hours after administration. Unchanged drug was the major component found in plasma, and no major metabolites were detected in the plasma. Total radioactivity recovered over a 4-day period from four of the six subjects averaged 82.5% and 13.2% of the dose in the urine and feces, respectively. Excretion into urine was rapid; most of the radioactivity was excreted during the first 8 hours. Five radioactive chromatographic peaks, a cyclic amide and four polar metabolites, were detected in 0- to 24-hour urine samples. Similarity of metabolite profiles between humans and cynomolgus monkeys permitted use of this animal model to generate samples after a high dose for structure elucidation. Liquid chromatography/mass spectrometry (LC/MS) analysis of monkey urine samples indicated that the four polar metabolites were two pairs of diastereoisomeric glucuronides whose molecular weight differed by two daltons. Enzyme hydrolysis, cochromatography, and LC/MS experiments resulted in the identification of a hydroxylated cyclic amide as one of the aglycones, which formed a pair of diastereoisomeric glucuronides after conjugation. Data also suggested that a dihydroxycyclic amide formed by the reduction of the ketone group that joins the phenyl rings formed the second pair of diastereoisomeric glucuronides. Further, incubation of various reference standards in control (blank) urine and buffer with and without creatinine indicated that the hydroxy cyclic amide released from enzyme hydrolysis can undergo ex vivo transformations to a condensation product between creatinine and an alpha-keto acid derivative of the hydroxy cyclic amide that is

  8. Effects of antipsychotics on cortisol, interleukin-6 and hippocampal perfusion in healthy volunteers.

    PubMed

    Handley, Rowena; Mondelli, Valeria; Zelaya, Fernando; Marques, Tiago; Taylor, Heather; Reinders, Antje A T S; Chaddock, Christopher; McQueen, Grant; Hubbard, Kathryn; Papadopoulos, Andrew; Williams, Steve; McGuire, Philip; Pariante, Carmine; Dazzan, Paola

    2016-07-01

    This randomized within-subject, double blind study aimed to compare the effects of a single dose of two different antipsychotics (haloperidol and aripiprazole) on cortisol, interleukin (IL)-6 and hippocampal regional Cerebral Blood Flow (rCBF) in the same 17 healthy male individuals. Subjects received a single dose of haloperidol (3mg), aripiprazole (10mg) and placebo, in a randomized order on three study appointments. We measured salivary cortisol levels at multiple time points, IL-6 levels from plasma samples, and resting cerebral blood flow (rCBF), using a pulsed continuous arterial spin labeling (pCASL) sequence (1.5T). We found significantly lower cortisol levels in the haloperidol condition (F(2,32)=5.78, p=0.007), than in either placebo (p=0.013; CI=0.45, 0.406) or aripiprazole (p=0.037; CI=-0.520, -0.014). Interleukin-6 levels were also lower following haloperidol (F(2,22)=4.19, p=0.048) in comparison with placebo (p=0.02; CI=0.14, 1.8), but not with aripiprazole. Finally, we found a greater rCBF in the right (peak voxel: T=6.47, p<0.0001) and left (peak voxel T=5.17, p<0.01) hippocampus following haloperidol compared with placebo, and at trend level also in the left hippocampus following aripiprazole compared with placebo (T=4.07, p=0.057). These differences in hippocampal rCBF after both antipsychotics were no longer evident (haloperidol) or present at trend level (aripiprazole), after controlling for cortisol and IL-6 levels. Our findings suggest that haloperidol can directly regulate the hypothalamic-pituitary-adrenal (HPA) axis and immune system through a pharmacological action via D2 receptor antagonism. Finally, our data suggest that the increased hippocampal rCBF is a manifestation of the reduction in IL-6 and cortisol which follows the administration of haloperidol. PMID:27112637

  9. Ethyl glucuronide concentrations in hair: a controlled alcohol-dosing study in healthy volunteers.

    PubMed

    L Crunelle, Cleo; Cappelle, Delphine; Yegles, Michel; De Doncker, Mireille; Michielsen, Peter; Dom, Geert; van Nuijs, Alexander L N; Maudens, Kristof E; Covaci, Adrian; Neels, Hugo

    2016-03-01

    Ethyl glucuronide (EtG) is a minor phase II metabolite of alcohol that accumulates in hair. It has been established as a sensitive marker to assess the retrospective consumption of alcohol over recent months using a cut-off of ≥7 pg/mg hair to assess repeated alcohol consumption. The primary aim was to assess whether amounts of alcohol consumed correlated with EtG concentrations in hair. Additionally, we investigated whether the current applied cut-off value of 7 pg/mg hair was adequate to assess the regular consumption of low-to-moderate amounts of alcohol. A prospective controlled alcohol-dosing study in 30 healthy individuals matched on age and gender. Individuals were instructed to drink no alcohol (N = 10), 100 g alcohol per week (N = 10) or 150 g alcohol per week (N = 10) for 12 consecutive weeks, before and after which hair was collected. Throughout the study, compliance to daily alcohol consumption was assessed by analyzing urine EtG three times weekly. Participants in the non-drinking group had median EtG concentrations of 0.5 pg/mg hair (interquartile range (IQR) 1.7 pg/mg; range < 0.21-4.5 pg/mg). Participants consuming 100 and 150 g alcohol per week showed median EtG concentrations of 5.6 pg/mg hair (IQR 4.7 pg/mg; range 2.0-9.8 pg/mg) and 11.3 pg/mg hair (IQR 5.0 pg/mg; range 7.7-38.9 pg/mg), respectively. Hair EtG concentrations between the three study groups differed significantly from one another (p < 0.001). Hair EtG concentrations can be used to differentiate between repeated (low-to-moderate) amounts of alcohol consumed over a long time period. For the assessment of repeated alcohol use, we propose that the current cut-off of 7 pg/mg could be re-evaluated. PMID:26549114

  10. Inter- and intrasubject variability of the inflammatory response to segmental endotoxin challenge in healthy volunteers.

    PubMed

    Holz, O; Tan, L; Schaumann, F; Müller, M; Scholl, D; Hidi, R; McLeod, A; Krug, N; Hohlfeld, J M

    2015-12-01

    Segmental endotoxin challenge with lipopolysaccharide (LPS) can be used as a pharmacodynamic model to safely induce a transient airway inflammation in the peripheral lung of healthy subjects and to test the anti-inflammatory efficacy of investigational new drugs. In contrast to whole lung LPS challenge only a fraction of the dose is required that can be precisely administered to a specific lung region and a vehicle challenged segment as an intra-subject control can be included. The aim of this study was to assess the intra- and inter-individual variability of the response to segmental LPS challenge for the appropriate design and power calculation of future clinical trials. Two cohorts with 10 subjects each underwent two segmental LPS challenges within five weeks. The inflammatory response was evaluated in bronchoalveolar lavage (BAL) fluid at 6 (cohort 1) and 24 h (cohort 2) both in the LPS and in a vehicle challenged segment, as well as in plasma for up to 26 h post LPS challenge. While the cytokine response was more pronounced at 6 h, the influx of neutrophils and monocytes dominated at 24 h; e.g. neutrophils increased from a median (inter-quartile range, IQR) of 0.14 (0.16) and 0.09 (0.08)x10(4) cells/mL BAL fluid at baseline to 10.2 (17.1) and 19.3 (15.9)x10(4) cells/mL 24 h after the two separate challenges. The within-subject variability was higher than the between-subject variability for most of the markers. However, sample size estimations based on the variability of outcome variables found lower or equal numbers with cross-over designs compared to parallel group designs for cellular markers at 24 h and cytokine variables at 6 h. The segmental LPS challenge model was safe. Future study designs have to balance between burden to the study subjects (4 versus 2 bronchoscopies), variability (within-versus between-subject), and the desired outcome variable (cells versus chemo/cytokine). PMID:26545873

  11. It is possible to perform a double-blind hyperbaric session: a double-blinded randomized trial performed on healthy volunteers.

    PubMed

    Jansen, T; Mortensen, C R; Tvede, M F

    2009-01-01

    In hyperbaric medicine, blinded trials are remarkably few, making results susceptible to criticism. The scopes of the present study are to present a method for a double-blinded randomized clinical study and evaluate the validity of the method in a hyperbaric setting. Twenty-two healthy volunteers with no diving experience were included. The volunteers were randomized either to a "therapeutic pressure" group (15 msw, 253 kPa) or to a "placebo" group (2 msw, 120 kPa). The two profiles were made equal regarding noise, temperature and ventilation. The volunteers were asked whether they had been exposed to placebo or therapeutic pressure. They were asked to present their certainness of the answer on a visual analogue scale (VAS). Fisher's exact test calculates a probability of P = 0,328, which indicates that the volunteers have no valid opinion as to whether they were exposed to 15 msw or to 2 msw. It is found that it is possible to perform a blinded treatment on healthy volunteers with no prior diving experience. PMID:20112525

  12. A randomised study in healthy volunteers to investigate the safety, tolerability and pharmacokinetics of idarucizumab, a specific antidote to dabigatran.

    PubMed

    Glund, Stephan; Moschetti, Viktoria; Norris, Stephen; Stangier, Joachim; Schmohl, Michael; van Ryn, Joanne; Lang, Benjamin; Ramael, Steven; Reilly, Paul

    2015-05-01

    Idarucizumab, a monoclonal antibody fragment that binds dabigatran with high affinity, is in development as a specific antidote for dabigatran. In this first-in-human, single-rising-dose study, we investigated the pharmacokinetics, safety and tolerability of idarucizumab. Healthy male volunteers aged 18-45 years received between 20 mg and 8 g idarucizumab as a 1-hour intravenous infusion in 10 sequential dose groups, or 1, 2 or 4 g idarucizumab as a 5-minute infusion. Subjects within each dose group were randomised 3:1 to idarucizumab or placebo. A total of 110 randomised subjects received study drug (27 placebo, 83 idarucizumab). Peak and total exposure to idarucizumab increased proportionally with dose. Maximum plasma concentrations were achieved near the end of infusion, followed by a rapid decline, with an initial idarucizumab half-life of ~45 minutes. For the 5-minute infusions, this resulted in a reduction of plasma concentrations to less than 5 % of peak within 4 hours. Idarucizumab (in the absence of dabigatran) had no effect on coagulation parameters or endogenous thrombin potential. Overall adverse event (AE) frequency was similar for idarucizumab and placebo, and no relationship with idarucizumab dose was observed. Drug-related AEs (primary endpoint) were rare (occurring in 2 placebo and 3 idarucizumab subjects) and were mostly of mild intensity; none of them resulted in study discontinuation. In conclusion, the pharmacokinetic profile of idarucizumab meets the requirement for rapid peak exposure and rapid elimination, with no effect on pharmacodynamic parameters. Idarucizumab was safe and well tolerated in healthy males.

  13. Quantitative analysis of hyperpolarized 129Xe ventilation imaging in healthy volunteers and subjects with chronic obstructive pulmonary disease.

    PubMed

    Virgincar, Rohan S; Cleveland, Zackary I; Kaushik, S Sivaram; Freeman, Matthew S; Nouls, John; Cofer, Gary P; Martinez-Jimenez, Santiago; He, Mu; Kraft, Monica; Wolber, Jan; McAdams, H Page; Driehuys, Bastiaan

    2013-04-01

    In this study, hyperpolarized (129) Xe MR ventilation and (1) H anatomical images were obtained from three subject groups: young healthy volunteers (HVs), subjects with chronic obstructive pulmonary disease (COPD) and age-matched controls (AMCs). Ventilation images were quantified by two methods: an expert reader-based ventilation defect score percentage (VDS%) and a semi-automated segmentation-based ventilation defect percentage (VDP). Reader-based values were assigned by two experienced radiologists and resolved by consensus. In the semi-automated analysis, (1) H anatomical images and (129) Xe ventilation images were both segmented following registration to obtain the thoracic cavity volume and ventilated volume, respectively, which were then expressed as a ratio to obtain the VDP. Ventilation images were also characterized by generating signal intensity histograms from voxels within the thoracic cavity volume, and heterogeneity was analyzed using the coefficient of variation (CV). The reader-based VDS% correlated strongly with the semi-automatically generated VDP (r = 0.97, p < 0.0001) and with CV (r = 0.82, p < 0.0001). Both (129) Xe ventilation defect scoring metrics readily separated the three groups from one another and correlated significantly with the forced expiratory volume in 1 s (FEV1 ) (VDS%: r = -0.78, p = 0.0002; VDP: r = -0.79, p = 0.0003; CV: r = -0.66, p = 0.0059) and other pulmonary function tests. In the healthy subject groups (HVs and AMCs), the prevalence of ventilation defects also increased with age (VDS%: r = 0.61, p = 0.0002; VDP: r = 0.63, p = 0.0002). Moreover, ventilation histograms and their associated CVs distinguished between subjects with COPD with similar ventilation defect scores, but visibly different ventilation patterns.

  14. Electromyographic activity of trunk and hip muscles during stabilization exercises in four-point kneeling in healthy volunteers

    PubMed Central

    Vleeming, Andry; Bouche, Katie G.; Mahieu, Nele N.; Vanderstraeten, Guy G.; Danneels, Lieven A.

    2006-01-01

    Stabilization exercises are intended to optimize function of the muscles that are believed to govern trunk stability. Debate exists whether certain muscles are more important than others in optimally performing these exercises. Thirty healthy volunteers were asked to perform three frequently prescribed stabilization exercises in four-point kneeling. The electromyographic activity of different trunk and hip muscles was evaluated. Average amplitudes obtained during the exercises were normalized to the amplitude in maximal voluntary contraction (% MVIC). During all three exercises, the highest relative muscle activity levels (> 20% MVIC) were consistently found in the ipsilateral lumbar multifidus and gluteus maximus. During both the single leg extension (exercise 1) and the leg and arm extension exercise (exercise 2) the contralateral internal oblique and ipsilateral external oblique reached high levels (> 20%MVIC). During exercise 2 there were also high relative activity levels of the ipsilateral lumbar part and the contralateral thoracic part of the iliocostalis lumborum and the contralateral lumbar multifidus. During the leg and arm extension exercise with contralateral hip flexion (exercise 3) there were high relative muscle activity levels of all back muscles, except for the latissimus dorsi muscle. The lowest relative muscle activity levels (< 10% MVIC) were found in the rectus abdominis and the ipsilateral internal oblique during all exercises, and in the contralateral gluteus maximus during exercises 1 and 2. The results of this study show that in exercises in four-point kneeling performed by healthy subjects, hip and trunk muscles seem to work together in a harmonious way. This shows that when relative activity of muscles is measured, both “global and local” muscles function together in order to stabilize the spine. PMID:16896840

  15. Acute effects of different types of oil consumption on endothelial function, oxidative stress status and vascular inflammation in healthy volunteers.

    PubMed

    Tousoulis, Dimitris; Papageorgiou, Nikolaos; Antoniades, Charalambos; Giolis, Anastasios; Bouras, George; Gounari, Panagiota; Stefanadi, Elli; Miliou, Antigoni; Psaltopoulou, Theodora; Stefanadis, Christodoulos

    2010-01-01

    Consumption of different types of oil may have different effects on cardiovascular risk. The exact role of maize oil, cod liver oil, soya oil and extra virgin olive oil on endothelial function, oxidative stress and inflammation is unknown. We evaluated the effect of acute consumption of these types of oil on endothelial function, oxidative stress and inflammation in healthy adults. Thirty-seven healthy volunteers were randomised to receive an oral amount of each type of oil or water. Endothelial function was evaluated by gauge-strain plethysmography at baseline and 1, 2 and 3 h after consumption. Oxidative stress status was determined by total lipid peroxides (PEROX), while inflammatory process was estimated by measuring the soluble form of vascular adhesion molecule 1. Serum levels of the two previous markers were measured at baseline and 3 h after oil consumption. Reactive hyperaemia (RH) was significantly decreased after maize oil consumption compared with controls (P < 0.05). However, the consumption of cod liver oil and soya oil induced a significant improvement of RH after 1 h, compared with controls (P < 0.05). There was no significant effect of any type of oil consumption on endothelium-independent dilatation, total lipid PEROX and vascular adhesion molecule 1 serum levels. Consumption of maize oil leads to impaired endothelial function, while soya oil and cod liver oil slightly improve endothelial function. However, all types of oils did not affect inflammatory process and systemic oxidative stress, suggesting that their effect on endothelial function may not be mediated by free radicals bioavailability.

  16. Socioeconomic status is associated with striatal dopamine D2/D3 receptors in healthy volunteers but not in cocaine abusers.

    PubMed

    Wiers, Corinde E; Shokri-Kojori, Ehsan; Cabrera, Elizabeth; Cunningham, Samantha; Wong, Christopher; Tomasi, Dardo; Wang, Gene-Jack; Volkow, Nora D

    2016-03-23

    Positron emission tomography (PET) studies in animals and humans have shown that social status is associated with striatal dopamine D2/D3 receptor (D2/D3R) availability. That is, higher social hierarchy and higher scores on questionnaires assessing social status correlated positively with striatal D2/D3R availability in animals and humans respectively. Furthermore, subordinate monkeys were vulnerable to cocaine self-administration, suggesting that alternations in social hierarchy can change D2/D3R availability and vulnerability to cocaine use. Here, we investigated whether socioeconomic status (SES) measured with the Hollingshead scale is associated with striatal D2D/3R availability using [(11)C]raclopride PET in 38 cocaine abusers and 42 healthy controls matched for age and education. Compared to controls, cocaine abusers showed lower D2/D3R availability in the caudate, putamen and ventral striatum (all p≤0.001). Despite matching groups for education, SES scores were lower in cocaine abusers than controls (p<0.001). In the control group only, SES scores significantly correlated with D2/D3R in caudate (r=0.35, p=0.024) and putamen (r=0.39, p=0.011) but not in ventral striatum (p=0.61); all corrected for age. The study confirms that SES is associated with striatal D2/D3R availability in healthy human volunteers. However, reductions in D2/D3R availability in cocaine abusers may be driven by factors other than SES such as chronic cocaine exposure. PMID:26828302

  17. A Novel Magnetic Stimulator Increases Experimental Pain Tolerance in Healthy Volunteers - A Double-Blind Sham-Controlled Crossover Study

    PubMed Central

    Kortekaas, Rudie; Konopka, Karl-Heinz; Harbers, Marten; van der Hoeven, Johannes H.; van Wijhe, Marten; Aleman, André; Maurits, Natasha M.

    2013-01-01

    The ‘complex neural pulse’TM (CNP) is a neuromodulation protocol employing weak pulsed electromagnetic fields (PEMF). A pioneering paper reported an analgesic effect in healthy humans after 30 minutes of CNP-stimulation using three nested whole head coils. We aimed to devise and validate a stimulator with a novel design entailing a multitude of small coils at known anatomical positions on a head cap, to improve applicability. The main hypothesis was that CNP delivery with this novel device would also increase heat pain thresholds. Twenty healthy volunteers were enrolled in this double-blind, sham-controlled, crossover study. Thirty minutes of PEMF (CNP) or sham was applied to the head. After one week the other treatment was given. Before and after each treatment, primary and secondary outcomes were measured. Primary outcome was heat pain threshold (HPT) measured with thermal quantitative sensory testing. Other outcomes were warmth detection threshold, and aspects of cognition, emotion and motor performance. As hypothesized heat pain threshold was significantly increased after the PEMF stimulation. All other outcomes were unaltered by the PEMF but there was a trend level reduction of cognitive performance after PEMF stimulation as measured by the digit-symbol substitution task. Results from this pilot study suggest that our device is able to stimulate the brain and to modulate its function. This is in agreement with previous studies that used similar magnetic field strengths to stimulate the brain. Specifically, pain control may be achieved with PEMF and for this analgesic effect, coil design does not appear to play a dominant role. In addition, the flexible configuration with small coils on a head cap improves clinical applicability. Trial Registration Dutch Cochrane Centre NTR1093 PMID:23620795

  18. Upper Gastrointestinal Symptoms Are More Frequent in Female than Male Young Healthy Japanese Volunteers as Evaluated by Questionnaire

    PubMed Central

    Kawakubo, Hiroharu; Tanaka, Yuichiro; Tsuruoka, Nanae; Hara, Megumi; Yamamoto, Koji; Hidaka, Hidenori; Sakata, Yasuhisa; Shimoda, Ryo; Iwakiri, Ryuichi; Kusano, Motoyasu; Fujimoto, Kazuma

    2016-01-01

    Background/Aims Upper gastrointestinal symptoms are more frequent and severe in female than in male outpatients in Japan. This study compared the upper gastrointestinal symptoms between healthy male and female young adult volunteers using a questionnaire. Methods In total, 581 third-grade medical students at Saga Medical School aged 22 to 30 years underwent upper gastrointestinal endoscopy and completed a questionnaire (frequency scale for symptoms of gastroesophageal reflux disease) from 2007 to 2013. Of these 581 students, 298 who were negative for Helicobacter pylori infection and had no particular lesions on endoscopic examination were enrolled in the present evaluation. A symptom was defined as positive when the subject evaluated the frequency of the symptom as sometimes, often, or always. Results The subjects comprised of 163 males (average age, 23.7 years) and 135 females (average age, 23.1 years). Upper gastrointestinal symptoms were more frequent in the females (75 of 135, 55.6%) than males (69 of 163, 42.3%; P < 0.05), with a high score for 4 symptoms (bloated stomach, heavy feeling in the stomach after meals, subconscious rubbing of the chest with the hand, and feeling of fullness while eating meals). Of the 144 subjects (69 males and 75 females) who complained of these symptoms, the females complained of dysmotility symptoms more often than did the males, but this was not true for reflux symptoms. Conclusions This study suggests that females develop upper gastrointestinal symptoms more frequently than do males among the young healthy Japanese population. PMID:26755685

  19. Inter- and intra-operator reliability and repeatability of shear wave elastography in the liver: a study in healthy volunteers.

    PubMed

    Hudson, John M; Milot, Laurent; Parry, Craig; Williams, Ross; Burns, Peter N

    2013-06-01

    This study assessed the reproducibility of shear wave elastography (SWE) in the liver of healthy volunteers. Intra- and inter-operator reliability and repeatability were quantified in three different liver segments in a sample of 15 subjects, scanned during four independent sessions (two scans on day 1, two scans 1 wk later) by two operators. A total of 1440 measurements were made. Reproducibility was assessed using the intra-class correlation coefficient (ICC) and a repeated measures analysis of variance. The shear wave speed was measured and used to estimate Young's modulus using the Supersonics Imagine Aixplorer. The median Young's modulus measured through the inter-costal space was 5.55 ± 0.74 kPa. The intra-operator reliability was better for same-day evaluations (ICC = 0.91) than the inter-operator reliability (ICC = 0.78). Intra-observer agreement decreased when scans were repeated on a different day. Inter-session repeatability was between 3.3% and 9.9% for intra-day repeated scans, compared with to 6.5%-12% for inter-day repeated scans. No significant difference was observed in subjects with a body mass index greater or less than 25 kg/m(2).

  20. Whole-Brain In-vivo Measurements of the Axonal G-Ratio in a Group of 37 Healthy Volunteers

    PubMed Central

    Mohammadi, Siawoosh; Carey, Daniel; Dick, Fred; Diedrichsen, Joern; Sereno, Martin I.; Reisert, Marco; Callaghan, Martina F.; Weiskopf, Nikolaus

    2015-01-01

    The g-ratio, quantifying the ratio between the inner and outer diameters of a fiber, is an important microstructural characteristic of fiber pathways and is functionally related to conduction velocity. We introduce a novel method for estimating the MR g-ratio non-invasively across the whole brain using high-fidelity magnetization transfer (MT) imaging and single-shell diffusion MRI. These methods enabled us to map the MR g-ratio in vivo across the brain's prominent fiber pathways in a group of 37 healthy volunteers and to estimate the inter-subject variability. Effective correction of susceptibility-related distortion artifacts was essential before combining the MT and diffusion data, in order to reduce partial volume and edge artifacts. The MR g-ratio is in good qualitative agreement with histological findings despite the different resolution and spatial coverage of MRI and histology. The MR g-ratio holds promise as an important non-invasive biomarker due to its microstructural and functional relevance in neurodegeneration. PMID:26640427

  1. Bioequivalence evaluation of two roxithromycin formulations in healthy human volunteers by high performance liquid cromatography coupled to tandem mass spectrometry.

    PubMed

    Motta, M; Ribeiro, W; Ifa, D R; Moares, M E; Moraes, M O; Corrado, A P; De Nucci, G

    1999-01-01

    The bioequivalence of two different formulations containing roxithromycin (SPE-712-1). Oral suspension 300 mg/15 mL as test formulation and Rotram, tablets 300 mg as reference formulation, both by Schering Plough S.A., Brazil) was evaluated in 24 healthy volunteers of both sexes (12 male and 12 female). The study was conducted open with randomized two-period crossover design and a 14-day washout period. Each subject received 300 mg of each roxithromycin formulation. Plasma samples were obtained over a 72-hour interval and roxithromycin concentrations were analyzed by combined LC-MS/MS with positive ion electrospray ionization using selected ion monitoring method. From the plasma roxithromycin concentration vs time curves the following pharmacokinetic parameters were obtained: AUC(0-72 h), AUC(0-infinity), Cmax, t1/2 ratios and tmax individual differences. The 90% for confidence interval (CI) of geometric mean SPE-712-L/Rotram individual percent ratio were 105.0-128.3% for AUC(0-72 h), and 78.4-96.9 for Cmax. Although this 90% CI were marginally outside the interval proposed by the Food and Drug Administration, the probability assessed by the two-one sided West for ratios was included in the 0.8-1.25 interval, as we concluded that SPE-712-L oral suspension formulation was bioequivalent to Rotram tablet formulation for the extent and rate of absorption.

  2. The Effect of Chronic Alprazolam Intake on Memory, Attention, and Psychomotor Performance in Healthy Human Male Volunteers

    PubMed Central

    Chowdhury, Zahid Sadek; Morshed, Mohammed Monzur; Shahriar, Mohammad; Bhuiyan, Mohiuddin Ahmed; Islam, Sardar Mohd. Ashraful

    2016-01-01

    Alprazolam is used as an anxiolytic drug for generalized anxiety disorder and it has been reported to produce sedation and anterograde amnesia. In the current study, we randomly divided 26 healthy male volunteers into two groups: one group taking alprazolam 0.5 mg and the other taking placebo daily for two weeks. We utilized the Cambridge Neuropsychological Test Automated Battery (CANTAB) software to assess the chronic effect of alprazolam. We selected Paired Associates Learning (PAL) and Delayed Matching to Sample (DMS) tests for memory, Rapid Visual Information Processing (RVP) for attention, and Choice Reaction Time (CRT) for psychomotor performance twice: before starting the treatment and after the completion of the treatment. We found statistically significant impairment of visual memory in one parameter of PAL and three parameters of DMS in alprazolam group. The PAL mean trial to success and total correct matching in 0-second delay, 4-second delay, and all delay situation of DMS were impaired in alprazolam group. RVP total hits after two weeks of alprazolam treatment were improved in alprazolam group. But such differences were not observed in placebo group. In our study, we found that chronic administration of alprazolam affects memory but attentive and psychomotor performance remained unaffected. PMID:27462136

  3. Granulocyte colony-stimulating factor administration to healthy volunteers: analysis of the immediate activating effects on circulating neutrophils.

    PubMed

    de Haas, M; Kerst, J M; van der Schoot, C E; Calafat, J; Hack, C E; Nuijens, J H; Roos, D; van Oers, R H; von dem Borne, A E

    1994-12-01

    In four healthy volunteers, we analyzed in detail the immediate in vivo effects on circulating neutrophils of subcutaneous administration of 300 micrograms of granulocyte colony-stimulating factor (G-CSF). Neutrophil activation was assessed by measurement of degranulation. Mobilization of secretory vesicles was shown by a decrease in leukocyte alkaline phosphatase content of the circulating neutrophils. Furthermore, shortly postinjection, Fc gamma RIII was found to be upregulated from an intracellular pool that we identified by immunoelectron microscopy as secretory vesicles. Intravascular release of specific granules was shown by increased plasma levels of lactoferrin and by upregulation of the expression of CD66b and CD11b on circulating neutrophils. Moreover, measurement of fourfold elevated plasma levels of elastase, bound to its physiologic inhibitor alpha 1-antitrypsin, indicated mobilization of azurophil granules. However, no expression of CD63, a marker of azurophil granules, was observed on circulating neutrophils. G-CSF--induced mobilization of secretory vesicles and specific granules could be mimicked in whole blood cultures in vitro, in contrast to release of azurophil granules. Therefore, we postulate that the most activated neutrophils leave the circulation, as observed shortly postinjection, and undergo subsequent stimulation in the endothelial microenvironment, resulting in mobilization of azurophil granules. Our data demonstrate that G-CSF should be regarded as a potent immediate activator of neutrophils in vivo.

  4. The impact of multi-walled carbon nanotubes with different amount of metallic impurities on immunometabolic parameters in healthy volunteers.

    PubMed

    Vitkina, T I; Yankova, V I; Gvozdenko, T A; Kuznetsov, V L; Krasnikov, D V; Nazarenko, A V; Chaika, V V; Smagin, S V; Tsatsakis, A Μ; Engin, A B; Karakitsios, S P; Sarigiannis, D A; Golokhvast, K S

    2016-01-01

    The impact of two types of multi-walled carbon nanotubes (MWCNTs) (12-14 nm) with different content of metallic impurities (purified and unpurified nanotubes) on peroxidation processes, the status of immune cells in healthy volunteers and gene expression combined to pathway analysis was studied in vitro. From the study it was shown that the main mechanism of action for both types of MWCNTs is induction of oxidative stress, the intensity of which is directly related to the amount of metallic impurities. Unpurified MWCNTs produced twice as high levels of oxidation than the purified CNTs inducing thus more intense mitochondrial dysfunction. All the above were also verified by gene expression analysis of 2 different human cellular cultures (lung epithelium and keratinoma cells) and the respective pathway analysis; modulation of genes activating the NFkB pathway is associated to inflammatory responses. This may cause a perturbation in the IL-6 signaling pathway in order to regulate inflammatory processes and compensate for apoptotic changes. A plausible hypothesis for the immunological effects observed in vivo, are considered as the result of the synergistic effect of systemic (mediated by cells of the routes of exposure) and local inflammation (blood cells).

  5. A pilot, first-in-human, pharmacokinetic study of 9cUAB30 in healthy volunteers.

    PubMed

    Kolesar, Jill M; Hoel, Ryan; Pomplun, Marcia; Havighurst, Tom; Stublaski, Jeanne; Wollmer, Barbara; Krontiras, Helen; Brouillette, Wayne; Muccio, Donald; Kim, Kyungmann; Grubbs, Clinton J; Bailey, Howard E

    2010-12-01

    9cUAB30 is a synthetic analog of 9-cis-retinoic acid with chemopreventive activity in cell lines and in animal models. The purpose of this first-in-human evaluation of 9cUAB30 was to evaluate the single-dose pharmacokinetic profile and toxicity of the compound in healthy volunteers at 3 dose levels. This study enrolled 14 patients to receive a single dose of 5, 10, or 20 mg of 9cUAB30. Plasma and urine samples were collected to assess 9cUAB30 concentrations by a validated LC/MS MS method. 9cUAB30 was well tolerated, with 1 patient experiencing grade 2 toxicity and no grade 3 or 4 toxicities reported. T(max) occurred approximately 3 hours after dose administration with the plasma half-life ranging from 2.79 to 7.21 hours. AUC increased linearly across the examined dose range of 5 to 20 mg; C(max) was proportional to the log of the dose. The plasma clearance ranged from 25 to 39 L/h compared to the renal clearance which ranged from 0.018 to 0.103 L/h. 9cUAB30 has a favorable toxicity and pharmacokinetic profile, with oral availability and primarily hepatic metabolism. Further dose ranging studies with once a day dosing are underway.

  6. Pharmacokinetics and safety of recombinant anti-RhD in healthy RhD-negative male volunteers.

    PubMed

    Bichler, J; Spycher, M O; Amstutz, H-P; Andresen, I; Gaede, K; Miescher, S

    2004-04-01

    In this first-in-man study, we assessed the pharmacokinetics, safety and tolerability of MonoRho, a human recombinant monoclonal anti-RhD immunoglobulin G1 (IgG1) antibody. Eighteen RhD-negative healthy male volunteers were randomized in two groups to receive a single administration of 300 micro g of MonoRho either intravenously or intramuscularly. There were no symptoms of allergic or anaphylactic type reaction in any subject, and there was no evidence of any MonoRho-related changes in laboratory safety parameters. None of the subjects mounted a detectable immune response to MonoRho. Serum samples were obtained up to 91 days after injection to measure anti-D IgG concentrations by flow cytometry. After intramuscular administration of MonoRho, anti-D IgG concentrations gradually increased reaching peak levels after a mean of 3.4 days. After 3 weeks, the mean anti-D IgG concentrations after intravenous and intramuscular administration became virtually equal to each other and remained so thereafter. In both the treatment groups, the mean elimination half-life was about 18 days and thus similar to that described for plasma-derived anti-D IgG. The bioavailability of MonoRho after intramuscular administration was estimated as 46%. The excellent tolerability and safety of MonoRho as well as its expected elimination half-life supports the continued clinical development of this compound.

  7. A randomized placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers

    PubMed Central

    Faruqi, Shoaib; Wright, Caroline; Thompson, Rachel; Morice, Alyn H

    2014-01-01

    Aims The examination of cough reflex sensitivity through inhalational challenge can be utilized to demonstrate pharmacological end points. Here we compare the effect of butamirate, dextromethorphan and placebo on capsaicin-induced cough in healthy volunteers. Methods In this randomized, placebo-controlled, six way crossover study the effect of dextromethrophan 30 mg, four doses of butamirate and placebo was evaluated on incremental capsaicin challenges performed at baseline and 2, 4, 6, 8, 12 and 24 h following dosing. The primary end point was the area under the curve (AUC(0,12h)) of log10 C5 from pre-dose to 12 h after dosing. Plasma butamirate metabolites were analyzed to evaluate pharmacokinetic and pharmacodynamic relationships. Results Thirty-four subjects (13 males, median age 25 years) completed the study. Cough sensitivity decreased from baseline in all arms of the study. Dextromethorphan was superior to placebo (P = 0.01) but butamirate failed to show significant activity with maximum attenuation at the 45 mg dose. There was no apparent relationship between pharmacokinetic and pharmacodynamic parameters for butamirate. Conclusions We have demonstrated for the first time that dextromethorphan attenuates capsaicin challenge confirming its broad activity on the cough reflex. The lack of efficacy of butamirate could be due to formulation issues at higher doses. PMID:24995954

  8. Bioequivalence evaluation of two brands of furosemide 40 mg tablets (Salurin and Lasix) in healthy human volunteers.

    PubMed

    Najib, Naji; Idkaidek, Nasir; Beshtawi, M; Bader, Mohammed; Admour, Isra'; Alam, S Mahmood; Zaman, Q; Dham, Ruwayda

    2003-09-01

    A randomized, two-way, crossover, bioequivalence study was conducted in 24 fasting, healthy, male volunteers to compare two brands of furosemide 40 mg tablets, Salurin (Julphar, UAE) as test and Lasix (Hoechst AG, Germany) as reference product. The study was performed at the International Pharmaceutical Research Centre (IPRC), in a joint venture with Al-Mowasah Hospital, Amman, Jordan. One tablet of either formulation was administered with 240 ml of water after a 10 h overnight fast. After dosing, serial blood samples were collected for a period of 12 h. Plasma harvested from blood was analysed for furosemide by a validated HPLC method. Various pharmacokinetic parameters including AUC(0-t), AUC(0-infinity), C(max), T(max), T(1/2), and elimination rate constant were determined from plasma concentrations of both formulations. Statistical modules (ANOVA and 90% confidence intervals) were applied to AUC(0-t), AUC(0-infinity), and C(max) to assess the bioequivalence of the two brands which revealed no significant difference between them, and 90% CI fell within the US FDA accepted bioequivalence range of 80%-125%. Based on these statistical inferences, Salurin was found to be bioequivalent to Lasix.

  9. Comparative bioavailability of two brands of atenolol 100 mg tablets (Tensotin and Tenormin) in healthy human volunteers.

    PubMed

    Najib, Naji M; Idkaidek, Nasir; Adel, Ayman; Mohammed, B; Al-Masri, Sahar; Admour, Isra'; Alam, S Mahmood; Dham, Ruwayda; Qumaruzaman

    2005-01-01

    A bioequivalence study of two oral formulations of 100 mg atenolol was carried out in 24 healthy volunteers following a single dose, two-sequence, cross-over randomized design at the International Pharmaceutical Research Centre (IPRC), as a joint venture with Al-Mowasah Hospital, Amman, Jordan. The two formulations were Tensotin (Julphar, UAE) as test and Tenormin (Zeneca, UK) as reference product. Both test and reference tablets were administered with 240 ml of water to each subject after an overnight fast on 2 treatment days separated by a 1 week washout period. After dosing, serial blood samples were collected for a period of 36 h. Whole blood was analysed for atenolol by a sensitive, reproducible and accurate HPLC method with fluorescence detection capable of detecting atenolol in the range of 20-1600 ng/ml with a limit of quantitation of 20 ng/ml. Various pharmacokinetic parameters including AUC0-t, AUC0-proportional to), Cmax, Tmax, T1/2 and lambdaZ were determined from blood concentrations of both formulations and found to be in good agreement with reported values. AUC0-t, AUC0-proportional to), and Cmax were tested for bioequivalence after log-transformation of data using ANOVA and 90% confidence interval and were found within the acceptable range of 80%-125%. Based on these statistical inferences, it was concluded that Tensotin is bioequivalent to Tenormin.

  10. Bioequivalence evaluation of two brands of gliclazide 80 mg tablets (Glyzide & Diamicron)--in healthy human volunteers.

    PubMed

    Najib, Naji; Idkaidek, Nasir; Beshtawi, M; Bader, Mohammed; Admour, Isra'; Alam, S Mahmood; Zaman, Q; Dham, Ruwayda

    2002-07-01

    A randomized, two-way, crossover, bioequivalence study in 24 fasting, healthy, male volunteers was conducted to compare two brands of gliclazide 80 mg tablets, Glyzide (Julphar, UAE) as test and Diamicron (Servier Industries, France) as reference product. The study was performed at the International Pharmaceutical Research Centre (IPRC), in joint venture with Speciality Hospital, Amman, Jordan. The drug was administered with 240 ml of 20% glucose solution after a 10 h overnight fasting. After dosing, serial blood samples were collected for a period of 48 h. Plasma harvested from blood was analyzed for gliclazide by validated HPLC method. Various pharmacokinetic parameters including AUC(0-t), AUC(0- proportional, variant), C(max), T(max), T(1/2), and elimination rate constant were determined from plasma concentrations of both formulations. Statistical modules (ANOVA and 90% confidence intervals) were applied to AUC(0-t), AUC(0- proportional, variant), and C(max) for bioequivalence evaluation of the two brands which revealed no significant difference between them, and 90% CI fell within US FDA accepted bioequivalence range of 80-125%. Based on these statistical inferences, Glyzide was judged bioequivalent to Diamicron.

  11. Calcitonin Gene-Related Peptide Modulates Heat Nociception in the Human Brain - An fMRI Study in Healthy Volunteers

    PubMed Central

    Asghar, Mohammad Sohail; Becerra, Lino; Larsson, Henrik B. W.; Borsook, David; Ashina, Messoud

    2016-01-01

    Background Intravenous infusion of calcitonin-gene-related-peptide (CGRP) provokes headache and migraine in humans. Mechanisms underlying CGRP-induced headache are not fully clarified and it is unknown to what extent CGRP modulates nociceptive processing in the brain. To elucidate this we recorded blood-oxygenation-level-dependent (BOLD) signals in the brain by functional MRI after infusion of CGRP in a double-blind placebo-controlled crossover study of 27 healthy volunteers. BOLD-signals were recorded in response to noxious heat stimuli in the V1-area of the trigeminal nerve. In addition, we measured BOLD-signals after injection of sumatriptan (5-HT1B/1D antagonist). Results Brain activation to noxious heat stimuli following CGRP infusion compared to baseline resulted in increased BOLD-signal in insula and brainstem, and decreased BOLD-signal in the caudate nuclei, thalamus and cingulate cortex. Sumatriptan injection reversed these changes. Conclusion The changes in BOLD-signals in the brain after CGRP infusion suggests that systemic CGRP modulates nociceptive transmission in the trigeminal pain pathways in response to noxious heat stimuli. PMID:26990646

  12. [A relative bioavailability study of 2 oral formulations of omeprazole after their administration in repeated doses to healthy volunteers].

    PubMed

    Richards, J P; Gimeno, M; Moreland, T A; McEwen, J

    1999-04-01

    To determine the relative bioavailability of Ulceral (study formula) with respect to Losec (reference standard formula) and establish their bioequivalence daily doses of 20 mg of omeprazole were given during 5 consecutive days to 24 healthy volunteers. No significant differences were observed in the area under the curve (AUC0-t), a parameter directly related to the inhibition of acid secretion induced by omeprazole. The confidence interval of 90% for the difference between the two formulations for AUC0-t was within the interval of acceptance (0.80-1.25). The confidence interval for the difference between the two formulations for Cmax were also within the range of acceptance (0.70-1.43). In relation to the time for achieving (Cmax (tmax), the difference between the two formulations and the confidence interval of 95% for the tmax was 0.75 (-0.5-1.75) h indicating that no significant differences were observed between the two treatments. This study confirms the bioequivalence of Ulceral with the standard reference formulation as well as the tolerability of the two formulae. PMID:10349786

  13. The impact of multi-walled carbon nanotubes with different amount of metallic impurities on immunometabolic parameters in healthy volunteers.

    PubMed

    Vitkina, T I; Yankova, V I; Gvozdenko, T A; Kuznetsov, V L; Krasnikov, D V; Nazarenko, A V; Chaika, V V; Smagin, S V; Tsatsakis, A Μ; Engin, A B; Karakitsios, S P; Sarigiannis, D A; Golokhvast, K S

    2016-01-01

    The impact of two types of multi-walled carbon nanotubes (MWCNTs) (12-14 nm) with different content of metallic impurities (purified and unpurified nanotubes) on peroxidation processes, the status of immune cells in healthy volunteers and gene expression combined to pathway analysis was studied in vitro. From the study it was shown that the main mechanism of action for both types of MWCNTs is induction of oxidative stress, the intensity of which is directly related to the amount of metallic impurities. Unpurified MWCNTs produced twice as high levels of oxidation than the purified CNTs inducing thus more intense mitochondrial dysfunction. All the above were also verified by gene expression analysis of 2 different human cellular cultures (lung epithelium and keratinoma cells) and the respective pathway analysis; modulation of genes activating the NFkB pathway is associated to inflammatory responses. This may cause a perturbation in the IL-6 signaling pathway in order to regulate inflammatory processes and compensate for apoptotic changes. A plausible hypothesis for the immunological effects observed in vivo, are considered as the result of the synergistic effect of systemic (mediated by cells of the routes of exposure) and local inflammation (blood cells). PMID:26683310

  14. Influence of food on the oral bioavailability of deramciclane from film-coated tablet in healthy male volunteers.

    PubMed

    Drabant, Sándor; Nemes, Katalin Balogh; Horváth, Viola; Tolokán, Antal; Grézal, Gyula; Anttila, Markku; Gachályi, Béla; Kanerva, Harri; Al-Behaisi, Samar; Horvai, George; Klebovich, Imre

    2004-11-01

    The effect of a high-fat meal on the oral bioavailability of deramciclane 30 mg tablet was evaluated in 18 healthy male volunteers in a randomised, single dose, two-way crossover study. The drug was administered following an overnight fast or a standardised high-fat breakfast. The plasma concentrations of deramciclane and N-desmethylderamciclane were determined by using a validated HPLC-MS -MS/MS method. An effect of food on the bioavailability was indicated if the 90% confidence interval (CI) for the ratio of geometric means of fed and fasted treatments was not contained in the equivalence limit of 0.8-1.25 for AUC and C(max). The ratios of the mean C(max) and AUC(0-infinity) values of deramciclane were 1.24 (90% CI 1.12-1.38) and 1.31 (90% CI 1.21-1.41) in fed versus fasted subjects, which overlapped but exceeded the equivalence limit. In contrast to the parent compound, the 90% CI of the mean ratios for AUC(0-infinity) and C(max) of N-desmethylderamciclane were within the predefined range. The 24 and 31% increase in C(max) and AUC(0-infinity) of deramciclane, respectively, under fed condition is modest and probably has no clinical significance since it is relatively small compared to the inter-individual variability of these parameters.

  15. Local blanching after epicutaneous application of EMLA cream. A double-blind randomized study among 50 healthy volunteers.

    PubMed

    Villada, G; Zetlaoui, J; Revuz, J

    1990-01-01

    EMLA cream is a topical formulation based upon the eutectic mixture of lidocaine and prilocaine and is used in clinical settings to produce local analgesia after application under occlusive dressing. A blanching reaction has been reported to occur locally after application, but it is not clear whether this reaction is caused by the anesthetic mixture, by the vehicle or the occlusion. We studied this blanching reaction in 50 healthy volunteers in a double-blind randomized assay: EMLA versus placebo, under occlusive dressing for 1 h, each subject being his own control. We found 33 cases (66%) of blanching after application of EMLA cream versus 3 cases (6%) after placebo, this difference being highly significant. Blanching was observed without delay, after removal of the dressing, and was very transient, disappearing in less than 3 h in all cases. We thus conclude that the blanching reaction is (1) frequent but very transient, and (2) determined by the anesthetic mixture included in EMLA cream and not by the vehicle alone, nor by the occlusion, since it is not found with the placebo. The precise mechanism of this reaction is unknown.

  16. Calcitonin gene-related peptide (CGRP) levels during glyceryl trinitrate (GTN)-induced headache in healthy volunteers.

    PubMed

    Kruuse, C; Iversen, H K; Jansen-Olesen, I; Edvinsson, L; Olesen, J

    2010-04-01

    The role of nitric oxide (NO) in migraine has been studied in the experimental glyceryl trinitrate (GTN)-infusion headache model. We hypothesized that GTN-induced headache may activate the trigeminovascular system and be associated with increased levels of sensory neuropeptides, including calcitonin gene-related peptide (CGRP). CGRP, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and somatostatin plasma levels were measured before and after placebo/sumatriptan injection and during GTN-induced headache. Following a double-blind randomized cross-over design, 10 healthy volunteers received subcutaneous sumatriptan 6 mg or placebo. This was succeeded by 20 min of GTN (0.12 µg kg(-1) min(-1)) infusion. At baseline no subject reported headache (using verbal rating scale from 0 to 10) and the jugular CGRP-like immunoreactivity (-LI) level was 18.6 ± 2.5 pmol/l. After a 20-min intravenous infusion of GTN 0.12 µg kg(-1) min(-1), median peak headache intensity was 4 (range 2-6) (P < 0.05), while jugular CGRP-LI levels were unchanged (19.0 ± 2.8 pmol/l; P > 0.05). There were no changes in VIP-, NPY- or somatostatin-LI. In conclusion, the NO donor GTN appears not to induce headache via immediate CGRP release.

  17. The Effect of Chronic Alprazolam Intake on Memory, Attention, and Psychomotor Performance in Healthy Human Male Volunteers.

    PubMed

    Chowdhury, Zahid Sadek; Morshed, Mohammed Monzur; Shahriar, Mohammad; Bhuiyan, Mohiuddin Ahmed; Islam, Sardar Mohd Ashraful; Bin Sayeed, Muhammad Shahdaat

    2016-01-01

    Alprazolam is used as an anxiolytic drug for generalized anxiety disorder and it has been reported to produce sedation and anterograde amnesia. In the current study, we randomly divided 26 healthy male volunteers into two groups: one group taking alprazolam 0.5 mg and the other taking placebo daily for two weeks. We utilized the Cambridge Neuropsychological Test Automated Battery (CANTAB) software to assess the chronic effect of alprazolam. We selected Paired Associates Learning (PAL) and Delayed Matching to Sample (DMS) tests for memory, Rapid Visual Information Processing (RVP) for attention, and Choice Reaction Time (CRT) for psychomotor performance twice: before starting the treatment and after the completion of the treatment. We found statistically significant impairment of visual memory in one parameter of PAL and three parameters of DMS in alprazolam group. The PAL mean trial to success and total correct matching in 0-second delay, 4-second delay, and all delay situation of DMS were impaired in alprazolam group. RVP total hits after two weeks of alprazolam treatment were improved in alprazolam group. But such differences were not observed in placebo group. In our study, we found that chronic administration of alprazolam affects memory but attentive and psychomotor performance remained unaffected. PMID:27462136

  18. Pharmacoscintigraphic and pharmacokinetic evaluation on healthy human volunteers of sustained-release floating minitablets containing levodopa and carbidopa.

    PubMed

    Goole, J; Van Gansbeke, B; Pilcer, G; Deleuze, Ph; Blocklet, D; Goldman, S; Pandolfo, M; Vanderbist, F; Amighi, K

    2008-11-19

    In this study, scintigraphic and pharmacokinetic studies were conducted on 10 healthy, fed volunteers. Two concepts of sustained-release floating minitablets--Levo-Form 1 (matrix) and 2 (coated)--were evaluated and compared to the marketed product Prolopa HBS 125. All the floating forms were radiolabelled with (111)In in order to evaluate their gastric residence time using gamma-scintigraphy. It was shown that the three formulations offered almost the same mean gastric residence time, which was about 240 min. Prolopa HBS 125 and Levo-Form 2 presented intragastric disintegration, which can lead to a more pronounced "peak & valley" effect on the plasma concentration-time profile of levodopa. In contrast, the plasma concentration-time profile of levodopa following the administration of Levo-Form 1 was more evenly distributed. Moreover, Levo-Form 1 provided the lowest variations between men and women in terms of AUC and C(max) values. Finally, when the same amount of inhibitors of extracerebral dopa decarboxylase--carbidopa and benserazide--had been administrated, the mean AUC, C(max) and T(max) values obtained for benserazide were lower than those obtained for carbidopa. PMID:18778758

  19. Validation of indirect calorimetry for measurement of energy expenditure in healthy volunteers undergoing pressure controlled non-invasive ventilation support.

    PubMed

    Siirala, Waltteri; Noponen, Tommi; Olkkola, Klaus T; Vuori, Arno; Koivisto, Mari; Hurme, Saija; Aantaa, Riku

    2012-02-01

    The aim of this validation study was to assess the reliability of gas exchange measurement with indirect calorimetry among subjects who undergo non-invasive ventilation (NIV). Oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured in twelve healthy volunteers. Respiratory quotient (RQ) and resting energy expenditure (REE) were then calculated from the measured VO2 and VCO2 values. During the measurement period the subjects were breathing spontaneously and ventilated using NIV. Two different sampling air flow values 40 and 80 l/min were used. The gas leakage from the measurement setup was assessed with a separate capnograph. The mean weight of the subjects was 93 kg. Their mean body mass index was 29 (range 22-40) kg/m2. There was no statistically significant difference in the measured values for VO2, VCO2, RQ and REE during NIV-supported breathing and spontaneous breathing. The change of sampling air flow had no statistically significant effect on any of the above parameters. We found that REE can be accurately measured with an indirect calorimeter also during NIV-supported breathing and the change of sampling air flow does not distort the gas exchange measurement. A higher sampling air flow in indirect calorimetry decreases the possibility for air leakages in the measurement system and increases the reliability of REE measurement. PMID:22207315

  20. Evaluation of symptoms and palatability in healthy volunteers after ingestion of an iced dessert by using different flavours.

    PubMed

    Gallo, A; Gasbarrini, G; Nicoletti, M; Montalto, M; Addolorato, G

    2009-01-01

    It is well-known that digestion has a pivotal role in maintaining a state of wellbeing. The influence of certain foods and some herbal drugs has been ascertained. Epidemiological data show that the Mediterranean diet, with a high consumption of fresh vegetables and fruit, mainly citrus, has a beneficial effect and plays a protective gastrointestinal role. Previously, we assessed the influence on the eventual occurrence of symptoms during digestion of an iced dessert containing a mixture of digestive plant extracts, citrus juices and liquors, showing that its ingestion does not cause significant gastrointestinal symptoms in healthy volunteers. Taking into consideration that sensory properties of food may also influence digestion, we also evaluated the palatability of the product. In order to evaluate the effect of different tastes on the digestive processes, we performed a further similar evaluation with two new flavours. The ingestion of these iced desserts at the end of the meal does not cause significant gastrointestinal symptoms. Moreover, palatability median score shows a good appreciation of the products. Therefore, the combination of digestive herbs, citrus juice and liquors in different flavours gives rise to a product with a positive mix of good palatability, favourable acceptance and herbal constituents, able to maintain a good digestive condition. PMID:19589295

  1. Pharmacokinetics of azithromycin and the combination of ivermectin and albendazole when administered alone and concurrently in healthy volunteers.

    PubMed

    Amsden, Guy W; Gregory, Thomas B; Michalak, Cheryl A; Glue, Paul; Knirsch, Charles A

    2007-06-01

    Azithromycin is a critical component of an integrated disease elimination program against trachoma. This study was conducted to evaluate whether azithromycin has a pharmacokinetic interaction with the combination of ivermectin and albendazole. Eighteen healthy volunteers were administered single doses of azithromycin, ivermectin/albendazole, and the combination of the three agents in random, crossover fashion. To assess the presence of interactions, test (combination) and reference (single dose) data were compared using an estimation approach. Compared with reference phases, the geometric mean values for the combination arm's azithromycin AUC(0-t) and C(max) were increased approximately 13% and 20%, respectively, albendazole AUC(0-t) decreased by approximately 3% and C(max) increased approximately 3%, and ivermectin AUC(0-t) and C(max) were increased 31% and 27%, respectively. Albendazole sulfoxide AUC(0-t) and C(max) were decreased approximately 16% and 14%, respectively. All treatments were well tolerated. The interactions for azithromycin and albendazole were minimal although the increase in ivermectin exposure requires further study. PMID:17556628

  2. Evaluation of the bioequivalence and pharmacokinetics of two formulations of secnidazole after single oral administration in healthy volunteers.

    PubMed

    Zhu, De Qiu; Hu, Kai Li; Tao, Wei Xing; Feng, Liang; Duan, Hu; Jiang, Xin Guo; Chen, Jun

    2007-01-01

    The pharmacokinetic parameters of two oral formulations of a 1 g dose of secnidazole (CAS 3366-95-8, secnidazole tablet as reference and another capsule preparation as test) were compared in an open-label, randomized, single oral dose, two-period cross-over design in 18 healthy volunteers under fasting conditions. Plasma concentrations of secnidazole were measured by a validated HPLC chromatographic assay. The parametric 90% confidence intervals of the geometric mean values of the test/reference ratios were 91.9% to 105.9% (point estimate: 99.39%) for AUC(0-infinity), 92.7% to 104.4% (point estimate: 98.61%) for AUC(0-t), 97.6% to 107.1% (point estimate: 102.31%) for C(max), being within the acceptance criteria for bioequivalence (80%-125%). T(max) values were analyzed by the nonparametric Wilcoxon test and the difference was not statistically significant. Therefore, it is concluded that the test and reference secnidazole formulations are bioequivalent for both the extent and the rate of absorption. PMID:18193695

  3. Orally given gastroprotective capsaicin does not modify aspirin-induced platelet aggregation in healthy male volunteers (human phase I examination).

    PubMed

    Sandor, B; Papp, J; Mozsik, Gy; Szolcsanyi, J; Keszthelyi, Zs; Juricskay, I; Toth, K; Habon, Tamas

    2014-12-01

    Capsaicin is a well-known component of red pepper. Recent studies have shown that capsaicin could prevent gastric ulcer provoked by various NSAID-s like acetylsalicylic acid (ASA). Primary objective of this human clinical phase I trial was to investigate whether two different doses of capsaicin co-administered with ASA could alter the inhibitory effect of ASA on platelet aggregation. 15 healthy male subjects were involved in the study and treated orally with 400 μg capsaicin, 800 μg capsaicin, 500 mg ASA, 400 μg capsaicin+500 mg ASA and 800 μg capsaicin+500 mg ASA. Blood was drawn before and 1, 2, 6 and 24 hours after the drug administration. After that epinephrine induced platelet aggregation was measured by optical aggregometry. Between treatments, volunteers had a 6-day wash-out period. Our results showed that capsaicin had no effect on platelet aggregation, while as expected, ASA monotherapy resulted in a significant and clinically effective platelet aggregation inhibition (p ≤ 0.001). The combined ASA-capsaicin therapies reached equivalent effectiveness in platelet aggregation inhibition as ASA monotherapy. Our investigation proved that capsaicin did not influence the inhibitory effect of ASA on platelet aggregation, thus the capsaicin-ASA treatment would combine the antiplatelet effect of ASA with the possible gastroprotection of capsaicin.

  4. Evaluation of the bioequivalence and pharmacokinetics of two formulations of rizatriptan after single oral administration in healthy volunteers.

    PubMed

    Chen, Jun; Jiang, Wen Ming; Xie, Yue Ling; Jin, Liang; Mei, Ni; Liang, Xin Guo

    2005-01-01

    The pharmacokinetic parameters of two oral formulations of rizatriptan (CAS 144034-80-0, a capsule preparation as test and rizatriptan tablet as reference), given at a single dose of 10 mg each, were compared in an open-label, randomized, single oral dose, two-period cross-over design in 20 healthy volunteers under fasting conditions. Plasma concentrations of rizatriptan were measured by a validated HPLC assay. The parametric 90% confidence intervals of the geometric mean values of the test/reference ratios were 91.9% to 101.9% (point estimate: 97.3%) for AUC(0-infinity), 93.0% to 102.2% (point estimate: 96.5%) for AUC(0-t), 90.1% to 100.0% (point estimate: 95.4%) for Cmax, being within the acceptance criteria for bioequivalence (80%-125%). Tmax values were analyzed by the nonparametric Wilcoxon test and the difference was not statistically significant. Therefore, it is concluded that the test and reference rizatriptan formulations are bioequivalent with regard to both the extent and the rate of absorption. PMID:16080273

  5. Combined effects of acute, very-low-dose ethanol and delta(9)-tetrahydrocannabinol in healthy human volunteers

    PubMed Central

    Ballard, Michael E.; de Wit, Harriet

    2011-01-01

    Rationale Previous studies examining the combined effects of ethanol and cannabis, or its primary psychoactive ingredient, Δ9-tetrahydrocannabinol (THC), have provided mixed results. Data from an in vitro study suggests that combined, sub-threshold doses of these drugs may interact to produce synergistic effects. Very low doses of the two drugs in combination have not been tested in humans. Materials and Methods This study assessed whether combinations of acute, very-low doses of ethanol and THC produce synergistic effects on subjective, cognitive, and physiological measures. Healthy volunteers (n=11) received capsules containing placebo or THC (2.5mg), and beverages containing placebo or ethanol (0.1 and 0.2g/kg) alone, and in combination, across separate sessions, in a within-subjects, randomized, double-blind design. During each session, participants completed measures of working memory, psychomotor ability, and simple reaction time, and provided subjective mood and drug effect ratings. Cardiovascular measures were obtained at regular intervals. Results As intended, when administered alone, these very-low doses of ethanol and THC had only moderate effects on isolated measures. The combined effects of these drugs were not synergistic, and in some cases appeared to be less-than-additive. Conclusions Our data provide no evidence for synergistic effects of acute combinations of very-low-dose ethanol and THC on subjective or physiologic response, or on cognitive performance. PMID:21110996

  6. Recombinant factor VIIa reverses the anticoagulant effect of the long-acting pentasaccharide idraparinux in healthy volunteers.

    PubMed

    Bijsterveld, Nick R; Vink, Roel; van Aken, Benien E; Fennema, Hein; Peters, Ron J G; Meijers, Joost C M; Büller, Harry R; Levi, Marcel

    2004-03-01

    We investigated whether the anticoagulant effect of idraparinux, a selective long-acting factor Xa inhibitor, could be neutralized by recombinant factor VIIa (rFVIIa) in healthy male volunteers. We performed a randomized, placebo-controlled trial, comparing idraparinux [7.5 mg subcutaneous (s.c.)] followed at 3 h by rFVIIa [90 microg/kg intravenous (i.v.)] (n = 6), or idraparinux (7.5 mg s.c) followed after 1 week by rFVIIa (90 microg/kg i.v.)(n = 6). rFVIIa, given 3 h after idraparinux, significantly reversed the increased thrombin generation time (TGT), the increased activated partial thromboplastin time (aPTT) and prothrombin time (PT), and the reduced prothrombin fragment 1+2 (F1+2) levels caused by idraparinux, although no clear effect of rFVIIa on the endogenous thrombin potential (ETP) was observed. One week after idraparinux, injection of rFVIIa resulted in a similar relative reduction of the remaining increased aPTT, PT and TGT, with correction to pre-idraparinux values. A clear increase of F1+2 was observed, together with a small increase in ETP. We conclude that rFVIIa has significant effects on the idraparinux-inhibited thrombin generation and clotting parameters. These results suggest that rFVIIa may be useful in serious bleeding complications in idraparinux treated patients.

  7. Biological and hemodynamic effects of low doses of fludrocortisone and hydrocortisone, alone or in combination, in healthy volunteers with hypoaldosteronism.

    PubMed

    Laviolle, B; Le Maguet, P; Verdier, M-C; Massart, C; Donal, E; Lainé, F; Lavenu, A; Pape, D; Bellissant, E

    2010-08-01

    Low doses of hydrocortisone (HC) and fludrocortisone (FC) administered together improve the prognosis after septic shock; however, there continues to be disagreement about the utility of FC for this indication. The biological and hemodynamic effects of HC (50 mg intravenously) and FC (50 microg orally) were assessed in 12 healthy male volunteers with saline-induced hypoaldosteronism in a placebo-controlled, randomized, double-blind, crossover study performed according to a 2 x 2 factorial design. HC and FC significantly decreased urinary sodium and potassium levels (from -58% at 4 h to -28% at 10 h and from -35% at 8 h to -24% at 12 h, respectively) with additive effects. At 4 h after administration, HC significantly increased cardiac output (+14%), decreased systemic vascular resistances (-14%), and slightly increased heart rate (+4 beats/min), whereas FC had no hemodynamic effect. At doses used in septic shock, HC induced greater mineralocorticoid effect than FC did. HC also induced transient systemic hemodynamic effects, whereas FC did not. New studies are required to better define the optimal dose of FC in septic shock.

  8. Neurobehavioral and neurophysiological effects after acute exposure to a single peak of 200 ppm toluene in healthy volunteers.

    PubMed

    Kobald, S Oliver; Wascher, Edmund; Blaszkewicz, Meinolf; Golka, Klaus; van Thriel, Christoph

    2015-05-01

    The solvent toluene has neurotoxic properties that are especially relevant in the working environment. Short-term exposure limits (STELs) vary from 50 ppm up to 300 ppm across countries but their acute effects remain elusive in humans. Several in vitro and in vivo studies elucidated that toluene acutely acts by perturbations of different neurotransmitter systems. More specifically visual evoked potentials (VEPs) of rats are decreased after acute toluene exposure, leading to the assumption that particularly visual attention processes might be a target of toluene in humans. Therefore a visual change detection task was applied to measure both neurobehavioral and neurophysiological effects by using electroencephalography (EEG) after a single peak exposure to 200 ppm toluene. Performance and event-related components of the EEG were examined before and after exposure in a toluene-exposed and a control group. Thirty-three young healthy volunteers participated in this study. The behavioral results of the experiment indicate that toluene impairs the rate of correct responses especially in task conditions in which an irrelevant distractor is given, while the response times did not differ between both groups. The neurophysiological findings hint toward a less efficient visual processing of behaviorally relevant stimuli and an increased distractibility by irrelevant distractors. Thus the present results are a promising starting point for further research specifically targeting visual attention after toluene exposure and the reconsideration of the presently very heterogeneous STELs.

  9. Pharmacokinetic Profiles of Active Components After Oral Administration of a Kampo Medicine, Shakuyakukanzoto, to Healthy Adult Japanese Volunteers.

    PubMed

    Sadakane, Chiharu; Watanabe, Junko; Fukutake, Miwako; Nisimura, Hiroaki; Maemura, Kazuya; Kase, Yoshio; Kono, Toru

    2015-11-01

    Shakuyakukanzoto (SKT), a traditional Japanese (Kampo) medicine, has been used by patients with muscle cramps and abdominal pains. In this trial, we analyzed plasma concentrations of active components after SKT was administered as a single oral dose of 2.5 or 5.0 g/day per person. The study was a randomized, open-label, two-arm, two-period, crossover trial conducted in healthy Japanese volunteers. Albiflorin (ALB), paeoniflorin (PAE), glycycoumarin (GCM), isoliquiritigenin (ILG), glycyrrhetic acid (GA), and glycyrrhetic acid-3-O-monoglucuronide were targeted, and the plasma concentration of each component was measured using a liquid chromatography-tandem mass spectrometry method. The pharmacokinetic parameters were calculated, and the linearity was assessed. All targeted components were detected in the plasma after oral administration of SKT. ALB, PAE, GCM, and ILG were detected at an early stage. The linearity was observed for the maximum plasma concentration of GCM, ILG, and GA and for the area under the plasma concentration-time curve of GA. In this trial, we demonstrated for the first time in humans that these components were absorbed into the blood after oral administration of SKT. The results of this pharmacokinetic trial in humans are also important and useful for understanding the mechanism of action of SKT, verifying the active components predicted in basic research, and conducting pharmacokinetics and safety studies in the future. PMID:26211516

  10. Effects of grapefruit juice on cortisol metabolism in healthy male Chinese subjects.

    PubMed

    Xiao, Ya-Jie; Hu, Miao; Tomlinson, Brian

    2014-12-01

    Grapefruit juice (GFJ) inhibits intestinal CYP3A4 activity and it has been suggested that GFJ may also inhibit renal 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), which converts cortisol to cortisone. This study examined the effect of GFJ on the urinary excretion of cortisol, cortisone and 6β-hydroxycortisol (6β-OHC) and their ratios to asses these effects. Healthy male Chinese subjects took single doses of GFJ (200, 400, and 600 mL, respectively) at weekly intervals. Urine was collected over 24 h the day before and following GFJ intake. Subsequently, volunteers drank 400 mL GFJ for 7 days and urine was collected from 0 to 4 h daily. GFJ had dose-dependent effects on increasing cortisol excretion (P <0.05) and the ratio of cortisol to cortisone (P <0.005) and reducing 6β-OHC excretion (P <0.05) and the ratio of 6β-OHC to cortisol (P <0.005). There was no significant effect on cortisone excretion. Maximal effects were observed within 4 h after GFJ ingestion. Repeated doses had persistent but no cumulative effects. GFJ significantly reduced the ratio of 6β-OHC to cortisol. It increased the ratio of cortisol to cortisone and this appeared largely due to increased cortisol excretion related to impaired CYP3A4-mediated cortisol metabolism although a true inhibitory effect on 11β-HSD2 in the kidney cannot be excluded.

  11. Novel approach to quantify duodenogastric reflux in healthy volunteers and in patients with type I gastric ulcer.

    PubMed Central

    Müller-Lissner, S A; Fimmel, C J; Sonnenberg, A; Will, N; Müller-Duysing, W; Heinzel, F; Müller, R; Blum, A L

    1983-01-01

    A new method is described which allows simultaneous measurement of gastric emptying and duodenogastric reflux and avoids transpyloric intubation. After intragastric instillation of a liquid lipid meal in six healthy volunteers the fractional gastric emptying rate was 2.9 +/- 0.3 in the upright and 2.5 +/- 0.6 SEM X 10(-2)/min in the supine position, respectively (p greater than 0.5). The duodenogastric reflux rate (expressed as fraction of the intraduodenal amount of duodenal marker) was 0.30 (range 0.03-0.81) and 0.22 (0.01-0.55) X 10(-2)/min, respectively (p greater than 0.2). Atropine (40 micrograms/kg) decreased the supine gastric emptying rate to 1.1 +/- 0.2 (p less than 0.05) and increased the supine duodenogastric reflux rate to 2.74 (0.04-9.80) X 10(-2)/min (p less than 0.05). Fasting duodenogastric reflux rate was similar in the supine and upright position, 0.49 (0.04-0.89) and 0.42 (0.06-0.97) X 10(-2)/min, respectively (p greater than 0.5). Fractional gastric emptying rate was similar in 10 volunteers and 17 patients with type I gastric ulcer (2.1 +/- 0.4 vs 1.7 +/- 0.2 SEM X 10(-2)/min, p greater than 0.2). Their duodenogastric reflux rates were also similar, 0.65 (0.01-5.24) vs 1.10 (0.01-10.83) X 10(-2)/min (p greater than 0.5). We conclude therefore that (1) gastric emptying and both fasting and postprandial duodenogastric reflux are independent of the posture; (2) fasting and postprandial reflux are of similar magnitude; (3) atropine shows gastric emptying and increases duodenogastric reflux; and (4) patients with type I gastric ulcer have neither slowed gastric emptying nor increased duodenogastric reflux. PMID:6852631

  12. Comparison of gastric body and antral pH: a 24 hour ambulatory study in healthy volunteers.

    PubMed

    McLauchlan, G; Fullarton, G M; Crean, G P; McColl, K E

    1989-05-01

    Simultaneous ambulatory records of gastric antral and body pH were made over 24 hours in nine healthy volunteers by means of endoscopically positioned and anchored glass electrodes. Intragastric pH was temporarily raised after the endoscopy with the median pH value 30 minutes after the procedure being 3.9 (range 1.5-7.0) for the antrum and 4.1 (range 1.5-7.0) for the body. Daytime pH (median pH value between 12 00 h and 23 00 h) was lower in the antrum (median = 1.9, range 1.6-2.6) than in the body (median = 2.7, range 1.8-4.5) (p less than 0.05) and this was because of the rise in pH on eating being less marked in the antrum than in the body. The median peak pH recorded during the evening meal was only 4.1 (range 2.4-6.2) in the antrum compared with 6.3 (range 4.4-6.7) in the body (p less than 0.01). Preprandial pH (median value over the hour prior to the evening meal) was similar in the antrum (median = 1.9, range 1.2-2.5) and body (median = 1.9, range 1.3-2.8). Night-time pH (median pH value between 23 00 h and 05 00 h) in six subjects remained low and was similar in the antrum (median = 1.4, range 1.2-1.7) and body (median = 1.3, range 1.1-1.7). In two subjects, however, there were episodes of raised night-time pH which were more marked in the antrum than in the body. Antral biopsies showed gastritis in four of the nine normal volunteers, which in three was associated with the presence of campylobacter-like organisms. This study shows the significant regional variations in day and night-time intragastric pH.

  13. Amino acid metabolism during total parenteral nutrition in healthy volunteers: evaluation of a new amino acid solution.

    PubMed

    Berard, M P; Hankard, R; Cynober, L

    2001-10-01

    The aim of this study was to determine the metabolism and the tolerance of a new amino acid (AA) solution administered under conditions mimicking cyclical parenteral nutrition (PN) in humans. Eight healthy volunteers received peripheral PN for 10 h providing 10.5 mg N x kg(-1) x h(-1) and 2.0 kcal x kg(-1) x h(-1) (glucose-to-lipids ratio: 70/30%). For adaptation, a non-protein energy intake was increased progressively for 90 min; thereafter, AA infusion was started and maintained at a constant rate for 10 h. Plasma and urine concentrations of all the AAs were measured before, during and after the PN. For each given AA, the relation between plasma variations at the steady-state and infusion rate, plasma clearance (Cl), renal clearance (Clr), re-absorption rate (Reab) and, retention rate (Reten) were determined. The nitrogen balance (DeltaN) was calculated during the PN period. The results are presented as means+/-sem. All plasma AA concentrations decreased during the starting period of non-protein energy intake. The plasma AA concentrations reached a steady-state within 3 h upon AA infusion, except for glycine and lysine (6 h). At the steady state, the plasma concentrations of the infused AAs were closely correlated to their infusion rate (y= -18.3+1.5x, r(2)=0.92). The plasma glutamine concentration was maintained during the PN, which indicates that the solution might stimulate the de novo synthesis of this AA. When the PN was stopped, plasma levels of the AAs decreased, most of them returning to their basal levels, or significantly below for lysine (P<0.05), alanine (P<0.05), proline (P<0.01) and glutamine (P<0.05). No volunteer showed any adverse effect during the infusion period. DeltaN was: 0.8+/-0.5 gN/10 h. Metabolic characteristics for essential AAs were: Cl<0.5 l min(-1), Clr <1.5 ml x min(-1) Reab >or= 99%, Reten >or=99% and for non-essential AAs: Cl <0.6 l x min(-1) except aspartate (2.8+/-0.3 l x min(-1)), Clr < 3 ml x min(-1) except glycine (6

  14. Pharmacokinetics and extrapulmonary beta 2 adrenoceptor activity of nebulised racemic salbutamol and its R and S isomers in healthy volunteers

    PubMed Central

    Lipworth, B. J.; Clark, D. J.; Koch, P.; Arbeeny, C.

    1997-01-01

    BACKGROUND: Racemic salbutamol remains one of the most commonly used bronchodilators in the treatment of reversible airways obstruction. Data from animal and human studies suggest that the S-isomer, whilst contributing no bronchodilator activity, may induce increased bronchial hyperreactivity and may explain the adverse effects of regular racemic salbutamol on asthmatic disease control. The purpose of this study was to evaluate the dose-response effects of racemic (+/-) salbutamol and its R(-) and S(+) isomers in terms of pharmacokinetics and pharmacodynamics at extrapulmonary beta 2 adrenoceptors when given by the inhaled route to healthy volunteers. METHODS: Twelve healthy volunteers of mean age 20.6 years were studied in a double blind, placebo controlled, crossover design comparing cumulative doubling doses of nebulised R-salbutamol (R) and S-salbutamol (S) isomers (200 micrograms/400 micrograms/800 micrograms/1600 micrograms/3200 micrograms) and racemic salbutamol (RS) (400 micrograms/800 micrograms/1600 micrograms/3200 micrograms/6400 micrograms). Doses were administered at 20 minute intervals (t0/t20/t40/t60/t80) and measurements were made of extrapulmonary beta 2 responses as an increase in finger tremor and heart rate and fall in plasma potassium at baseline and each dose level (t0/t20/t40/t60/t80/t100). Plasma levels of salbutamol were measured at 15 minutes after each dose with a further sample at 30 minutes after the last dose (t110). RESULTS: Pharmacodynamics showed dose related beta 2 responses for R-salbutamol and RS-salbutamol but not for the S isomer, and a plateau in response was not reached within the administered dose range. No differences in responses were found between R-salbutamol and RS-salbutamol when compared on a 1:2 microgram basis. The effects of the S isomer were indistinguishable from those of placebo. For all beta 2 responses there were differences between R-salbutamol and S-salbutamol (for t100 response as change from placebo

  15. The effect of hyperglycemia on blood coagulation: In vitro, observational healthy-volunteer study using rotational thromboelastometry (ROTEM).

    PubMed

    Shin, Hyun-Jung; Na, Hyo-Seok; Lee, Soowon; Lee, Gwan-Woo; Do, Sang-Hwan

    2016-08-01

    We performed a study to investigate whether contamination of hemostasis samples with a glucose-containing solution might generate spurious results in rotational thromboelastometry (ROTEM) tests.Venous blood was taken from 12 healthy volunteers and divided into 4 specimen bottles, which were contaminated with different concentrations (0%, 5%, 10%, and 20%) of glucose solution.Significant lengthening of INTEMCT was observed in the 10% and 20% groups compared with baseline values (7.7% and 9%, P = 0.041 and P = 0.037, respectively). INTEMCFT increased by 20.1% in the 20% group (P = 0.005). INTEMα-angle and INTEMMCF decreased by 3.9% and 2.7%, respectively, in the 20% group (P = 0.010 and P = 0.049, respectively). EXTEMCFT was prolonged significantly, by 10.2%, 15.5%, and 25.6%, in the 5%, 10%, and 20% groups, respectively (P = 0.004, P < 0.001, and P < 0.001, respectively). EXTEMα-angle decreased significantly by 1.9%, 3.2%, and 4.0% in the 5%, 10%, and 20% groups, respectively (P = 0.014, P = 0.001, and P = 0.005, respectively). EXTEMMCF decreased by 3.4% in the 20% group (P = 0.023). FIBTEMMCF decreased by 9.2% and 17.5% in the 10% and 20% groups, respectively (P = 0.019 and P = 0.021, respectively). A significant correlation was observed between standard glucose solution contamination in the specimens and percentage variation of EXTEMCFT, EXTEMMCF, and FIBTEMMCF.To obtain accurate data from the ROTEM test regarding the hemostatic status of patients, specimens with suspected or known contamination should not be analyzed. PMID:27583903

  16. Mechanics of the carotid artery wall and baroreflex sensitivity after acute ethanol administration in young healthy volunteers.

    PubMed

    Fazio, M; Bardelli, M; Macaluso, L; Fiammengo, F; Mattei, P L; Bossi, M; Fabris, B; Fischetti, F; Pascazio, L; Candido, R; Carretta, R

    2001-09-01

    The effects of ethanol administered orally (300 mg/kg in 250 ml of water) or intravenously (7.5 mg.min(-1).kg(-1) in 250 ml of saline over 40 min) on common carotid haemodynamics, wall mechanics and baroreflex sensitivity were compared with the effects of the intravenous infusion of 250 ml of saline. Ethanol or saline was administered to 10 healthy volunteers after 30 min of supine rest, and measurements were obtained 40 min (median; range 34-46 min) after administration. After ethanol administration, the plasma alcohol level rose from 0 to 0.3+/-0.07 g/l. Mean arterial blood pressure had risen slightly at 20 min, but was normalized by 40 min, the time at which the haemodynamic study was performed. Heart rate decreased after infusion of either saline or alcohol, but was unchanged after oral ethanol administration. Both oral and intravenous ethanol administration were associated with significant decreases in baroreflex sensitivity, carotid shear stress and blood velocity, compared with resting values, while the mean carotid artery diameter was increased, and blood viscosity and mean blood flow were unchanged. No changes were observed in these parameters after saline administration. Ethanol, administered either intravenously or orally, increased the stiffness of the carotid artery and decreased the pulsatility (systo-diastolic changes) of its diameter. A direct, statistically significant correlation was found between the decrease in shear stress and the decrease in baroreflex heart rate control sensitivity after both modes of alcohol administration, while no such correlation was found between the increase in the Peterson elastic modulus and the decrease in carotid diameter pulsatility on the one hand or the decrease in baroreflex sensitivity on the other. In conclusion, reduced shear stress associated with vasodilatation of the carotid artery wall may contribute to the decrease in baroreflex sensitivity observed after acute ethanol administration.

  17. Pharmacokinetic study of a new oral buffered acetylsalicylic acid (ASA) formulation in comparison with plain ASA in healthy volunteers.

    PubMed

    Viganò, G; Garagiola, U; Gaspari, F

    1991-01-01

    A single-blind, randomized, crossover pharmacokinetic study was carried out to investigate the bioavailability of a new oral buffered 325 mg acetylsalicylic acid (ASA) formulation (ASPIRINA 03) in comparison with a 325 mg plain tablet. Twelve healthy volunteers of both sexes, aged between 20 and 37 years, received buffered or plain ASA on two separate occasions with a wash-out interval of at least two weeks. ASA and salicylic acid (SA) plasma levels were determined by a chromatographic method. The results showed no difference between the area under concentration time curve (AUC0-infinity) ASA values of both formulations (p = 0.19), and buffered ASA relative bioavailability was 102.49% (= bioequivalence). A significant difference was found between the AUC0-30 min ASA values: 90.5 micrograms. min/ml with buffered and 67.7 micrograms. min/ml with the plain tablet (p less than 0.05). The buffered ASA time of maximum concentration was shorter (28 +/- 8 min) than the plain one (38 +/- 19 min, p less than 0.05). The plasma concentrations and pharmacokinetic parameters of SA were not significantly different after the administration of the two ASA formulations. The plain ASA tablet had a significantly lower (p less than 0.05) dissolution rate than buffered ASA tablet. Moreover, the buffered ASA tablet significantly (p less than 0.01) increased the pH by 0.5 units. In conclusion, the bioavailability of the new oral buffered ASA was equivalent to that of plain ASA, but the plasma concentration peak was reached in a shorter time. PMID:1809699

  18. Effect of Tinospora cordifolia on physical and cardiovascular performance induced by physical stress in healthy human volunteers

    PubMed Central

    Salve, Bharat A.; Tripathi, Raakhi K.; Petare, Anup U.; Raut, Ashwinikumar A.; Rege, Nirmala N.

    2015-01-01

    Introduction: In Ayurveda Tinospora cordifolia (Willd.) Miers., has been used for its Rasayana, Deepana, Jwaranashana, Tridosha Shamaka properties. It is an immunomodulator, useful in stress, hyperlipidemia, pyrexia. T. cordifolia was evaluated for adaptogenic activity in healthy volunteers during exercise. Aims: The primary objective of this study was to evaluate the effect of T. cordifolia on physical performance, and secondary objectives were to evaluate muscle power, maximal oxygen consumption, and sympathetic activity in comparison with placebo when subjected to physical stress. Materials and Methods: A total of thirty participants were randomly assigned into three groups (n = 10 each) namely placebo, TC 150 and TC 300. Placebo group received maize starch capsule, TC 150 and TC 300 received 150 mg and 300 mg, respectively of T. cordifolia aqueous extract in capsule form once daily in the morning for 28 days. The assessment was performed at baseline visit, day 14 and 28. Physical stressors were cycle ergometer exercise, Jammer's hand-held dynamometer, and cold pressor tests. Physical performance evaluated was maximum distance and speed, oxygen consumption (VO2 max), and hand grip strength. Cardiovascular response was assessed by multiple heart rate (HR) and blood pressure (BP) measurements during each test. Results: On day 28, TC 150 mg group showed a significant increase in mean maximum speed compared to placebo. On day 14 and 28, TC 300 mg group showed a significant decrease in mean systolic BP (SBP) and HR on fixed workload exercise compared to placebo. There was significant increasing dose effect of both TC groups on SBP on day 14 and 28 and on HR on day 28 only. On day 14 and 28, TC 300 mg showed a significant decrease in mean HR on the cold pressor test, compared to placebo. Conclusion: T. cordifolia improved physical performance and suppressed over activation of the sympathetic nervous system showing its adaptogenic property. PMID:27313412

  19. Effect of heat-induced pain stimuli on pulse transit time and pulse wave amplitude in healthy volunteers.

    PubMed

    van Velzen, Marit H N; Loeve, Arjo J; Kortekaas, Minke C; Niehof, Sjoerd P; Mik, Egbert G; Stolker, Robert J

    2016-01-01

    Pain is commonly assessed subjectively by interpretations of patient behaviour and/or reports from patients. When this is impossible the availability of a quantitative objective pain assessment tool based on objective physiological parameters would greatly benefit clinical practice and research beside the standard self-report tests. Vasoconstriction is one of the physiological responses to pain. The aim of this study was to investigate whether pulse transit time (PTT) and pulse wave amplitude (PWA) decrease in response to this vasoconstriction when caused by heat-induced pain. The PTT and PWA were measured in healthy volunteers, on both index fingers using photoplethysmography and electrocardiography. Each subject received 3 heat-induced pain stimuli using a Temperature-Sensory Analyzer thermode block to apply a controlled, increasing temperature from 32.0 °C to 50.0 °C to the skin. After reaching 50.0 °C, the thermode was immediately cooled down to 32.0 °C. The study population was divided into 2 groups with a time-interval between the stimuli 20s or 60s. The results showed a significant (p  <  0.05) decrease of both PTT and PWA on the stimulated and contralateral side. Moreover, there was no significant difference between the stimulated and contralateral side. The time-interval of 20s was too short to allow PTT and PWA to return to baseline values and should exceed 40s in future studies. Heat-induced pain causes a decrease of PTT and PWA. Consequently, it is expected that, in the future, PTT and PWA may be applied as objective indicators of pain, either beside the standard self-report test, or when self-report testing is impossible.

  20. The effect of hyperglycemia on blood coagulation: In vitro, observational healthy-volunteer study using rotational thromboelastometry (ROTEM)

    PubMed Central

    Shin, Hyun-Jung; Na, Hyo-Seok; Lee, Soowon; Lee, Gwan-Woo; Do, Sang-Hwan

    2016-01-01

    Abstract We performed a study to investigate whether contamination of hemostasis samples with a glucose-containing solution might generate spurious results in rotational thromboelastometry (ROTEM) tests. Venous blood was taken from 12 healthy volunteers and divided into 4 specimen bottles, which were contaminated with different concentrations (0%, 5%, 10%, and 20%) of glucose solution. Significant lengthening of INTEMCT was observed in the 10% and 20% groups compared with baseline values (7.7% and 9%, P = 0.041 and P = 0.037, respectively). INTEMCFT increased by 20.1% in the 20% group (P = 0.005). INTEMα-angle and INTEMMCF decreased by 3.9% and 2.7%, respectively, in the 20% group (P = 0.010 and P = 0.049, respectively). EXTEMCFT was prolonged significantly, by 10.2%, 15.5%, and 25.6%, in the 5%, 10%, and 20% groups, respectively (P = 0.004, P < 0.001, and P < 0.001, respectively). EXTEMα-angle decreased significantly by 1.9%, 3.2%, and 4.0% in the 5%, 10%, and 20% groups, respectively (P = 0.014, P = 0.001, and P = 0.005, respectively). EXTEMMCF decreased by 3.4% in the 20% group (P = 0.023). FIBTEMMCF decreased by 9.2% and 17.5% in the 10% and 20% groups, respectively (P = 0.019 and P = 0.021, respectively). A significant correlation was observed between standard glucose solution contamination in the specimens and percentage variation of EXTEMCFT, EXTEMMCF, and FIBTEMMCF. To obtain accurate data from the ROTEM test regarding the hemostatic status of patients, specimens with suspected or known contamination should not be analyzed. PMID:27583903

  1. Nanosizing of a poorly soluble drug: technique optimization, factorial analysis, and pharmacokinetic study in healthy human volunteers

    PubMed Central

    Elsayed, Ibrahim; Abdelbary, Aly Ahmed; Elshafeey, Ahmed Hassen

    2014-01-01

    Context Diacerein (DCN) has low aqueous solubility (3.197 mg/L) and, consequently, low oral bioavailability (35%–56%). To increase both the solubility and dissolution rate of DCN while maintaining its crystalline nature, high pressure homogenization was used but with only a few homogenization cycles preceded by a simple bottom-up technique. Methods The nanosuspensions of DCN were prepared using a combined bottom-up/top-down technique. Different surfactants – polyvinyl alcohol, sodium deoxycholate, and sodium dodecyl sulfate – with different concentrations were used for the stabilization of the nanosuspensions. Full factorial experimental design was employed to investigate the influence of formulation variables on nanosuspension characteristics using Design-Expert® Software. Particle size (PS), zeta potential, saturation solubility, in vitro dissolution, and drug crystallinity were studied. Moreover, the in vivo performance of the optimized formula was assessed by bioavailability determination in healthy human volunteers. Results The concentration of surfactant had a significant effect on both the PS and polydispersity index values. The 1% surfactant concentration showed the lowest PS and polydispersity index values compared with other concentrations. Both type and concentration of surfactant had significant effects on the zeta potential. Formula F8 (containing 1% sodium deoxycholate) and Formula F12 (containing 1% sodium dodecyl sulfate) had the highest desirability values (0.952 and 0.927, respectively). Hence, they were selected for further characterization. The saturated solubility and mean dissolution time, in the case of F8 and F12, were significantly higher than the coarse drug powder. Techniques utilized in the nanocrystals’ preparation had no effect on DCN crystalline state. The selected formula (F12) showed a higher bioavailability compared to the reference market product with relative bioavailability of 131.4%. Conclusion The saturation

  2. Quantification of microscopic diffusion anisotropy disentangles effects of orientation dispersion from microstructure: applications in healthy volunteers and in brain tumors.

    PubMed

    Szczepankiewicz, Filip; Lasič, Samo; van Westen, Danielle; Sundgren, Pia C; Englund, Elisabet; Westin, Carl-Fredrik; Ståhlberg, Freddy; Lätt, Jimmy; Topgaard, Daniel; Nilsson, Markus

    2015-01-01

    The anisotropy of water diffusion in brain tissue is affected by both disease and development. This change can be detected using diffusion MRI and is often quantified by the fractional anisotropy (FA) derived from diffusion tensor imaging (DTI). Although FA is sensitive to anisotropic cell structures, such as axons, it is also sensitive to their orientation dispersion. This is a major limitation to the use of FA as a biomarker for "tissue integrity", especially in regions of complex microarchitecture. In this work, we seek to circumvent this limitation by disentangling the effects of microscopic diffusion anisotropy from the orientation dispersion. The microscopic fractional anisotropy (μFA) and the order parameter (OP) were calculated from the contrast between signal prepared with directional and isotropic diffusion encoding, where the latter was achieved by magic angle spinning of the q-vector (qMAS). These parameters were quantified in healthy volunteers and in two patients; one patient with meningioma and one with glioblastoma. Finally, we used simulations to elucidate the relation between FA and μFA in various micro-architectures. Generally, μFA was high in the white matter and low in the gray matter. In the white matter, the largest differences between μFA and FA were found in crossing white matter and in interfaces between large white matter tracts, where μFA was high while FA was low. Both tumor types exhibited a low FA, in contrast to the μFA which was high in the meningioma and low in the glioblastoma, indicating that the meningioma contained disordered anisotropic structures, while the glioblastoma did not. This interpretation was confirmed by histological examination. We conclude that FA from DTI reflects both the amount of diffusion anisotropy and orientation dispersion. We suggest that the μFA and OP may complement FA by independently quantifying the microscopic anisotropy and the level of orientation coherence.

  3. Comparative bioavailability study of cefixime (equivalent to 100 mg/5 ml) suspension (Winex vs Suprax) in healthy male volunteers.

    PubMed

    Asiri, Y A; Al-Said, M S; Al-Khamis, K I; Niazy, E M; El-Sayed, Y M; Al-Rashood, K A; Al-Yamani, M J; Alsarra, I A; Al-Balla, S A

    2005-10-01

    This investigation was carried out to evaluate the bioavailability of a new suspension formulation of cefixime (100 mg/5 ml), Winex, relative to the reference product, Suprax (100 mg/5 ml) suspension. The bio-availability study was carried out in 24 healthy male volunteers who received a single oral dose (200 mg) of the test (A) and the reference (B) products on 2 treatment days after an overnight fast of at least 10 hours. The treatment periods were separated by a one-week washout period. A randomized, balanced two-way crossover design was used. After dosing, serial blood samples were collected over a period of 16 hours. Plasma concentrations of cefixime were analyzed using a sensitive high-performance liquid chromatographic assay. The pharmacokinetic parameters for cefixime were determined using standard non-compartmental method. The parameters AUC(0-t), AUC(0-infinity), Cmax, Kel, t1/2 and Cmax/AUC(0-infinity) were analyzed statistically using raw and log-transformed data. The time to maximum concentration (tmax) was analyzed using raw data. The parametric 90% confidence intervals of the mean values of the pnfinity harmacokinetic parameters: AUC(0-t), AUC(0-infinity) Cmax, and Cmax/AUC(0-infinity) were within the range 80 - 125% which is acceptable for bioequivalence (using log-transformed data). The calculated 90% confidence intervals based on the ANOVA analysis for the mean test/reference ratios of AUC(0-t), AUC(0-infinity), Cmax, and Cmax/AUC(0-infinity) were 88.93 - 107.10%, 89.09 - 107.11%, 89.63 - 108.58% and 96.85 - 105.29%, respectively. The test formulation was found bioequivalent to the reference formulation with regard to AUC(0-t), AUC(0-infinity), and Cmax using the Schuirmann's two one-sided t-tests. Therefore, the two formulations were considered to be bioequivalent.

  4. Bioequivalence evaluation of two brands of metformin 500 mg tablets (Dialon & Glucophage)--in healthy human volunteers.

    PubMed

    Najib, Naji; Idkaidek, Nasir; Beshtawi, M; Bader, Mohammed; Admour, Isra'; Alam, S Mahmood; Zaman, Q; Dham, Ruwayda

    2002-10-01

    A randomized, two-way, crossover study was conducted in 24 fasting, healthy, male volunteers to compare the bioavailability of two brands of metformin 500 mg tablets; Dialon (Julphar, UAE) as test and Glucophage (Lipha Pharmaceutical Industries, France) as reference product. The study was performed at the International Pharmaceutical Research Centre (IPRC), in joint venture with Al-Mowasah Hospital, Amman, Jordan. The drug was administered with 240 ml of water after a 10-h overnight fasting on two treatment days separated by 1-week washout period. After dosing, serial blood samples were collected for a period of 30 h. Plasma harvested from blood was analyzed for metformin by validated HPLC method with UV-visible detector capable to detect metformin in the range of 0.05-5.0 microg/ml with limit of quantitation of 0.05 microg/ml. Various pharmacokinetic parameters including AUC(0-t), AUC(0-proportional to), C(max), T(max), T(1/2), and lambda(Z) were determined from plasma concentrations of both formulations and found to be in good agreement with reported values. AUC(0-t), AUC(0-proportional to) and C(max) were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence interval (97.9-110.8% for AUC(0-t), 97.4-110.7% for AUC(0-proportional to); 95.3-110.5% for C(max)) of test/reference ratio for these parameters were found within bioequivalence acceptance range of 80-125%. Based on these statistical inferences, it was concluded that Dialon is bioequivalent to Glucophage.

  5. Intra-Parenchymal Renal Resistive Index Variation (IRRIV) Describes Renal Functional Reserve (RFR): Pilot Study in Healthy Volunteers.

    PubMed

    Samoni, Sara; Nalesso, Federico; Meola, Mario; Villa, Gianluca; De Cal, Massimo; De Rosa, Silvia; Petrucci, Ilaria; Brendolan, Alessandra; Rosner, Mitchell H; Ronco, Claudio

    2016-01-01

    An increase of glomerular filtration rate after protein load represents renal functional reserve (RFR) and is due to afferent arteriolar vasodilation. Lack of RFR may be a risk factor for acute kidney injury (AKI), but is cumbersome to measure. We sought to develop a non-invasive, bedside method that would indirectly measure RFR. Mechanical abdominal pressure, through compression of renal vessels, decreases blood flow and activates the auto-regulatory mechanism which can be measured by a fall in renal resistive index (RRI). The study aims at elucidating the relationship between intra-parenchymal renal resistive index variation (IRRIV) during abdominal pressure and RFR. In healthy volunteers, pressure was applied by a weight on the abdomen (fluid-bag 10% of subject's body weight) while RFR was measured through a protein loading test. We recorded RRI in an interlobular artery after application of pressure using ultrasound. The maximum percentage reduction of RRI from baseline was compared in the same subject to RFR. We enrolled 14 male and 16 female subjects (mean age 38 ± 14 years). Mean creatinine clearance was 106.2 ± 16.4 ml/min/1.73 m(2). RFR ranged between -1.9 and 59.7 with a mean value of 28.9 ± 13.1 ml/min/1.73 m(2). Mean baseline RRI was 0.61 ± 0.05, compared to 0.49 ± 0.06 during abdominal pressure; IRRIV was 19.6 ± 6.7%, ranging between 3.1% and 29.2%. Pearson's coefficient between RFR and IRRIV was 74.16% (p < 0.001). Our data show the correlation between IRRIV and RFR. Our results can lead to the development of a "stress test" for a rapid screen of RFR to establish renal susceptibility to different exposures and the consequent risk for AKI.

  6. Eplerenone mimics features of the alternative activation in macrophages obtained from patients with heart failure and healthy volunteers.

    PubMed

    Łabuzek, Krzysztof; Liber, Sebastian; Bułdak, Łukasz; Krupej-Kędzierska, Joanna; Machnik, Grzegorz; Bobrzyk, Magdalena; Okopień, Bogusław

    2014-03-01

    Alternative activation of macrophages plays protective role in cardiac remodelling in heart failure and the activity of mineralocorticoid receptor may determine the phenotype of these cells. We examined the influence of eplerenone, aldosterone, and IL-4 on descriptors of alternative activation in blood monocytes collected from 19 patients with heart-failure and 20 healthy volunteers. “Heart failure” macrophages in comparison with “healthy” macrophages had increased mineralocorticoid activity, NO and reactive oxygen species production, expression of iNOS mRNA and protein, but decreased expression of arginase I and mannose receptor proteins, and activity of MnSOD and CuZnSOD. Aldosterone increased mineralocorticoid activity, NO and reactive oxygen species production, iNOS mRNA and protein expression, MnSOD and CuZnSOD activity. Eplerenone attenuated the effects of aldosterone on all but MnSOD and CuZnSOD variables. Eplerenone alone increased the production of NO, MnSOD and CuZnSOD activity, arginase I gene and protein expression, and mannose receptor gene and protein expression, but decreased mineralocorticoid activity only in “heart failure” macrophages. The latter suggests altered function of mineralocorticoid receptor in heart failure. Increased mineralocorticoid activity accounts for increased NO production, iNOS gene and protein expression but does not explain the increased basal reactive oxygen species production and decreased markers of alternative activation in “heart failure” macrophages. In the lack of change in basal mineralocorticoid activity, eplerenone increases markers of alternative activation in a mineralocorticoid receptor-independent manner. Because of changes in iNOS and NO variable, eplerenone induced qualitatively different activation of macrophages from that obtained with IL-4.

  7. Evaluation of the satiating properties of a nutraceutical product containing Garcinia cambogia and Ascophyllum nodosum extracts in healthy volunteers.

    PubMed

    Mayer, Marcos A; Finlayson, Graham; Fischman, Daniela; de Paz, Carolina; Telleriarte, Martín R; Ferrero, Alejandro J; Bobillo, Cecilia; Fernández, Belisario E

    2014-04-01

    A nutraceutical product composed of a combination of Garcinia cambogia, l-carnitine and a seaweed extract of Ascophyllum nodosum has been recently developed. The aim of the present study was to characterize its effects on subjective satiety sensations and food preferences in healthy volunteers. In a crossover design, 28 subjects (21 females and 7 males, aged 31 ± 5, BMI 22.6 ± 1.7) were randomly assigned to receive the active treatment (LIS) or placebo (PL) over one week. At the end of each treatment period, subjects were instructed to consume ad libitum a test meal. Food preferences and appetite sensations were evaluated by means of the Leeds Food Preferences Questionnaire and visual analog scales, before and after meal, over three hours. There were no differences in energy intake between study groups. LIS was associated with a reduction in subjective hunger sensations (p = 0.018) and to an increase in satiety (p = 0.02) and fullness (p = 0.01) ratings. The preference for high fat foods was reduced after consuming the test meal in both study groups. There was a significant effect of LIS treatment on food explicit liking and implicit wanting, as evidenced by an increase in preference for sweet foods (relative to savory foods; p = 0.03 and p = 0.004, respectively), but no differences were observed regarding the preference for low or high fat foods (NS). These results provide proof of principle for the satiating properties of a nutraceutical containing Garcinia cambogia, Ascophyllum nodosum extract and l-carnitine and suggest that it might be useful as an appetite modulator. PMID:24563084

  8. Comparable lumefantrine oral bioavailability when co-administered with oil-fortified maize porridge or milk in healthy volunteers.

    PubMed

    Mwebaza, Norah; Jerling, Markus; Gustafsson, Lars L; Obua, Celestino; Waako, Paul; Mahindi, Margarita; Ntale, Muhammad; Beck, Olof; Hellgren, Urban

    2013-07-01

    Co-administration of artemether-lumefantrine with milk is recommended to improve lumefantrine (L) absorption but milk may not be available in resource-limited settings. This study explored the effects of cheap local food in Uganda on oral bioavailability of lumefantrine relative to milk. In an open-label, four-period crossover study, 13 healthy adult volunteers were randomized to receive a single oral dose of artemether-lumefantrine (80 mg artemether/480 mg lumefantrine) with water, milk, maize porridge or maize porridge with oil on separate occasions. Plasma lumefantrine was assayed using high-performance liquid chromatography with ultraviolet detection. Pharmacokinetic exposure parameters were determined by non-compartmental methods using WinNonlin. Peak concentrations (Cmax ) and area under concentration-time curve restricted to 48 hr after single dosing (AUC(0-48) ) were selected for relative bioavailability evaluations using confidence interval approach for average bioequivalence. Lumefantrine exposure was comparable in milk and maize porridge plus oil study groups. When artemether-lumefantrine was administered with maize porridge plus oil, average bioequivalence ranges (means ratios 90% CI, 0.84-1.88 and 0.85-1.69 for Cmax and AUC(0-48) , respectively) were within and exceeded acceptance ranges relative to milk (90% CI, 0.80-1.25). Both fasted and maize porridge groups demonstrated similarly much lower ranges of lumefantrine exposures (bioinequivalence) relative to milk. If milk is not available, it is thus possible to recommend fortification of carbohydrate-rich food with little fat (maize porridge plus vegetable oil) to achieve similarly optimal absorption of lumefantrine after artemether-lumefantrine administration.

  9. Effects of 20 mg oral Δ9-tetrahydrocannabinol on the olfactory function of healthy volunteers*

    PubMed Central

    Walter, Carmen; Oertel, Bruno G; Ludyga, Dagmar; Ultsch, Alfred; Hummel, Thomas; Lötsch, Jörn

    2014-01-01

    Aims Olfactory loss impairs the patient's quality of life. In individualized therapies, olfactory drug effects gain clinical importance. Molecular evidence suggests that among drugs with potential olfactory effects is Δ9-tetrahydrocannabinol (THC), which is approved for several indications, including neuropathic pain or analgesia in cancer patients. The present study aimed at assessing the olfactory effects of THC to be expected during analgesic treatment. Methods The effects of 20 mg oral THC on olfaction were assessed in a placebo-controlled, randomized cross-over study in healthy volunteers. Using an established olfactory test (Sniffin' Sticks), olfactory thresholds, odour discrimination and odour identification were assessed in 15 subjects at baseline and 2 h after THC administration. Results Δ9-Tetrahydrocannabinol impaired the performance of subjects (n = 15) in the olfactory test. Specifically, olfactory thresholds were increased and odour discrimination performance was reduced. This resulted in a significant drop in composite threshold, discrimination, identification (TDI) olfactory score by 5.5 points (from 37.7 ± 4.2 to 32.2 ± 5.6, 95% confidence interval for differences THC vs. placebo, −7.8 to −2.0, P = 0.003), which is known to be a subjectively perceptible impairment of olfactory function. Conclusions Considering the resurgence of THC in medical use for several pathological conditions, the present results indicate that THC-based analgesics may be accompanied by subjectively noticeable reductions in olfactory acuity. In particular, for patients relying on their sense of smell, this might be relevant information for personalized therapy strategies. PMID:24802974

  10. Intra-Parenchymal Renal Resistive Index Variation (IRRIV) Describes Renal Functional Reserve (RFR): Pilot Study in Healthy Volunteers

    PubMed Central

    Samoni, Sara; Nalesso, Federico; Meola, Mario; Villa, Gianluca; De Cal, Massimo; De Rosa, Silvia; Petrucci, Ilaria; Brendolan, Alessandra; Rosner, Mitchell H.; Ronco, Claudio

    2016-01-01

    An increase of glomerular filtration rate after protein load represents renal functional reserve (RFR) and is due to afferent arteriolar vasodilation. Lack of RFR may be a risk factor for acute kidney injury (AKI), but is cumbersome to measure. We sought to develop a non-invasive, bedside method that would indirectly measure RFR. Mechanical abdominal pressure, through compression of renal vessels, decreases blood flow and activates the auto-regulatory mechanism which can be measured by a fall in renal resistive index (RRI). The study aims at elucidating the relationship between intra-parenchymal renal resistive index variation (IRRIV) during abdominal pressure and RFR. In healthy volunteers, pressure was applied by a weight on the abdomen (fluid-bag 10% of subject's body weight) while RFR was measured through a protein loading test. We recorded RRI in an interlobular artery after application of pressure using ultrasound. The maximum percentage reduction of RRI from baseline was compared in the same subject to RFR. We enrolled 14 male and 16 female subjects (mean age 38 ± 14 years). Mean creatinine clearance was 106.2 ± 16.4 ml/min/1.73 m2. RFR ranged between −1.9 and 59.7 with a mean value of 28.9 ± 13.1 ml/min/1.73 m2. Mean baseline RRI was 0.61 ± 0.05, compared to 0.49 ± 0.06 during abdominal pressure; IRRIV was 19.6 ± 6.7%, ranging between 3.1% and 29.2%. Pearson's coefficient between RFR and IRRIV was 74.16% (p < 0.001). Our data show the correlation between IRRIV and RFR. Our results can lead to the development of a “stress test” for a rapid screen of RFR to establish renal susceptibility to different exposures and the consequent risk for AKI. PMID:27458386

  11. Localization of MDMA-induced brain activity in healthy volunteers using low resolution brain electromagnetic tomography (LORETA).

    PubMed

    Frei, E; Gamma, A; Pascual-Marqui, R; Lehmann, D; Hell, D; Vollenweider, F X

    2001-11-01

    3,4-Methylenedioxymethamphetamine (MDMA; 'Ecstasy') is a psychostimulant drug producing heightened mood and facilitated social communication. In animal studies, MDMA effects are primarily mediated by serotonin (5-HT), but also by dopamine (DA) and possibly noradrenaline (NA). In humans, however, the neurochemical and neurophysiological basis of acute MDMA effects remains unknown. The distribution of active neuronal populations after administration of a single dose of MDMA (1.7 mg/kg) or placebo was studied in 16 healthy, MDMA-naïve volunteers. Thirty-one-channel scalp EEGs during resting with open and closed eyes was analyzed in the different EEG frequency bands. Scalp maps of power showed significant, global differences between MDMA and placebo in both eye conditions and all frequency bands. Low resolution brain electromagnetic tomography (LORETA) was used to compute 3D, functional images of electric neuronal activity from the scalp EEG data. MDMA produced a widespread decrease of slow and medium frequency activity and an increase of fast frequency activity in the anterior temporal and posterior orbital cortex, concomitant with a marked enhancement of mood, emotional arousal and increased extraversion. This activation of frontotemporal areas indicates that the observed enhancement of mood and possibly the increased extroversion rely on modulation of limbic orbitofrontal and anterotemporal structures known to be involved in emotional processes. Comparison of the MDMA-specific EEG pattern with that of various 5-HT, DA, and NA agonists indicates that serotonin, noradrenaline, and, to a lesser degree, dopamine, contribute to the effects of MDMA on EEG, and possibly also on mood and behavior.

  12. The tridimensional personality theory and pain: harm avoidance and reward dependence traits correlate with pain perception in healthy volunteers.

    PubMed

    Pud, Dorit; Eisenberg, Elon; Sprecher, Elliot; Rogowski, Zeev; Yarnitsky, David

    2004-02-01

    The aim of the present study was to examine the possible role of personality traits in determining the variability of pain perception among individuals. More specifically, it was intended to test whether or not the three personality dimensions suggested by Cloninger in 1987 - mainly harm avoidance (HA), but also reward dependence (RD), and novelty seeking (NS), can predict interpersonal differences in responsiveness to experimental pain. Seventy healthy volunteers participated in the study. Their personality traits were evaluated through Cloninger's tridimensional personality questionnaire (TPQ). Pain threshold (latency to pain onset), pain magnitude (VAS), and pain tolerance (time to withdrawal) were measured by using the cold pressor test. Bonferroni-adjusted correlations were found between HA and the pain parameters as follows: a negative correlation between HA and threshold (rho=-0.297, P(adj)=0.039); no significant correlation between HA and tolerance (rho=-0.219, P(adj)=0.207); and a trend for a positive correlation between HA and VAS (rho=0.266, P(adj)=0.081). Possible correlations between pain perception and the various possible combinations of high and low scoring for each of the three traits were also investigated. Correlations were found only for the combinations of high/low HA and high/low RD. The low HA/low RD combination demonstrated the lowest responsiveness to pain (VAS 65.2+/-21.4; tolerance 107.6+/-71.8 s), whereas the high HA/low RD combination was correlated with the highest responsiveness (VAS 83.3+/-10.8; tolerance 30.8+/-28.4 s). The results indicate that HA personality trait correlates best with pain responsiveness. As such, a high HA are likely to predict a heightened pain response. RD may modify this pattern. The possible relevant behavioral and neuro-chemical mechanisms are discussed.

  13. Pharmacokinetic study between a bilayer matrix fentalyl patch and a monolayer matrix fentanyl patch: single dose administration in healthy volunteers*

    PubMed Central

    Zecca, Ernesto; Manzoni, Andrea; Centurioni, Fabio; Farina, Alberto; Bonizzoni, Erminio; Seiler, Dan; Perrone, Tania; Caraceni, Augusto

    2015-01-01

    Aims Transdermal fentanyl is a well established treatment for cancer pain. The aim of the present study is to assess the relative bioavailability of fentanyl from two different transdermal systems by evaluating plasma drug concentrations after single administration of Fentalgon® (test), a novel bilayer matrix type patch, and Durogesic SMAT (reference), a monolayer matrix type patch. In the Fentalgon patch the upper 6% fentanyl reservoir layer maintains a stable concentration gradient between the lower 4% donor layer and the skin. The system provides a constant drug delivery over 72 h. Methods This was an open label, single centre, randomized, single dose, two period crossover clinical trial, that included 36 healthy male volunteers. The patches were applied to non-irritated and non-irradiated skin on the intraclavicular pectoral area. Blood samples were collected at different time points (from baseline to 120 h post-removal of the devices) and fentanyl concentrations were determined using a validated LC/MS/MS method. Bioequivalence was to be claimed if the 90% confidence interval of AUC(0,t) and Cmax ratios (test: reference) were within the acceptance range of 80–125% and 75–133%, respectively. Results The 90% confidence intervals of the AUC(0,t) ratio (116.3% [109.6, 123.4%]) and Cmax ratio (114.4% [105.8, 123.8%] were well included in the acceptance range and the Cmax ratio also met the narrower bounds of 80–125%. There was no relevant difference in overall safety profiles of the two preparations investigated, which were adequately tolerated, as expected for opioid-naïve subjects. Conclusions The new bilayer matrix type patch, Fentalgon®, is bioequivalent to the monolayer matrix type Durogesic SMAT fentanyl patch with respect to the rate and extent of exposure of fentanyl (Eudra/CT no. 2005-000046-36). PMID:25612845

  14. Intra-Parenchymal Renal Resistive Index Variation (IRRIV) Describes Renal Functional Reserve (RFR): Pilot Study in Healthy Volunteers.

    PubMed

    Samoni, Sara; Nalesso, Federico; Meola, Mario; Villa, Gianluca; De Cal, Massimo; De Rosa, Silvia; Petrucci, Ilaria; Brendolan, Alessandra; Rosner, Mitchell H; Ronco, Claudio

    2016-01-01

    An increase of glomerular filtration rate after protein load represents renal functional reserve (RFR) and is due to afferent arteriolar vasodilation. Lack of RFR may be a risk factor for acute kidney injury (AKI), but is cumbersome to measure. We sought to develop a non-invasive, bedside method that would indirectly measure RFR. Mechanical abdominal pressure, through compression of renal vessels, decreases blood flow and activates the auto-regulatory mechanism which can be measured by a fall in renal resistive index (RRI). The study aims at elucidating the relationship between intra-parenchymal renal resistive index variation (IRRIV) during abdominal pressure and RFR. In healthy volunteers, pressure was applied by a weight on the abdomen (fluid-bag 10% of subject's body weight) while RFR was measured through a protein loading test. We recorded RRI in an interlobular artery after application of pressure using ultrasound. The maximum percentage reduction of RRI from baseline was compared in the same subject to RFR. We enrolled 14 male and 16 female subjects (mean age 38 ± 14 years). Mean creatinine clearance was 106.2 ± 16.4 ml/min/1.73 m(2). RFR ranged between -1.9 and 59.7 with a mean value of 28.9 ± 13.1 ml/min/1.73 m(2). Mean baseline RRI was 0.61 ± 0.05, compared to 0.49 ± 0.06 during abdominal pressure; IRRIV was 19.6 ± 6.7%, ranging between 3.1% and 29.2%. Pearson's coefficient between RFR and IRRIV was 74.16% (p < 0.001). Our data show the correlation between IRRIV and RFR. Our results can lead to the development of a "stress test" for a rapid screen of RFR to establish renal susceptibility to different exposures and the consequent risk for AKI. PMID:27458386

  15. COMPARATIVE BIOAVAILABILITY OF A FIXED-DOSE COMBINATION TABLET OF OLMESARTAN MEDOXOMIL/HYDROCHLOROTHIAZIDE IN HEALTHY KOREAN VOLUNTEERS.

    PubMed

    Zheng, Renhua; Hwang, Ho Min; Kim, Bo-Hyung

    2016-01-01

    Combination therapy with diuretics and angiotensin II type 1 (AT1) receptor antagonist is frequently recommended for the control of blood pressure in hypertensive patients. This study was targeted to compare pharmacokinetic profiles of a new generic fixed-dose combination (FDC) tablet of olmesartan medoxomil/hydrochlorothiazide 20/12.5 mg and a reference formulation of Olmetec Plus 20/12.5 mg tablets in healthy volunteers. The study design was a randomized sequence and two-way crossover study in healthy subjects. They were to be randomly assigned to either one of the two sequence groups; each subject sequentially received a single oral dose of reference and test tablet with 7-day washout period. Blood sample was collected at pre-dose and at 0.33, 0.67, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 h post-dose. The blood concentrations were analyzed by LC-MS/MS. Both of the 90% CI for the treatment ratios (test/reference) of C(max) and AUC(last) were to be in the range of 0.800-1.250 with regards to olmesartan medoxomil and hydrochlorothiazide; the geometric mean ratios (test/reference) for olmesartan C(max) and AUC(last) were 0.979 (90% CI, 0.934-1.027) and 0.992 (0.946-1.041), respectively, and those for hydrochlorothiazide C(max) and AUC(last) were 0.966 (0.975-1.110) and 0.999 (0.963-1.038), respectively. No serious adverse events were reported during the study. The generic formulation of olmesartan medoxomil/hydrochlorothiazide 20/12.5 mg tablet was bioequivalent with the reference formulation of Olmetec Plus 20/12.5 mg tablet in regards to the pharmacokinetic parameters of olmesartan medoxomil and hydrochlorothiazide. Clinical Research Information Service (CRIS) Registration Number: KCT0001025. (https://cris.nih.go.kr/ Mar 18, 2014)

  16. Comparison of Endothelial Cell Phenotypic Markers of Late-Outgrowth Endothelial Progenitor Cells Isolated from Patients with Coronary Artery Disease and Healthy Volunteers

    PubMed Central

    Stroncek, John D.; Grant, Bryan S.; Brown, Melissa A.; Povsic, Thomas J.; Truskey, George A.

    2009-01-01

    The lack of easily isolated autologous endothelial cell (EC) sources is one of the major challenges with vascular tissue engineering interventions. This article examines the isolation and expansion of late-outgrowth endothelial progenitor cells (EPCs) from 50-mL samples of peripheral blood drawn from patients with significant coronary artery disease (CAD) and healthy young adult volunteers. In cases in which late-outgrowth EPCs were successfully isolated, the cells were assayed in vitro for their expression of EC markers, proliferation potential and ability to endothelialize synthetic materials, form new blood vessels, and produce nitric oxide. Late-outgrowth EPCs from patients with CAD and healthy volunteers exhibited critical EC markers and morphological characteristics that were analogous to a control population of human aortic ECs. To our knowledge, this is the first study to examine the suitability of late-outgrowth EPCs from patients with CAD for autologous endothelialization applications. PMID:19435420

  17. Interethnic variability of pharmacogenetic biomarkers in Mexican healthy volunteers: a report from the RIBEF (Ibero-American Network of Pharmacogenetics and Pharmacogenomics).

    PubMed

    Fricke-Galindo, Ingrid; Jung-Cook, Helgi; LLerena, Adrián; López-López, Marisol

    2016-06-01

    Mexico presents a complex population diversity integrated by Mexican indigenous (MI) (7% of Mexico's population) and Mexican mestizos (MMs). This composition highlights the importance of pharmacogenetic studies in Mexican populations. The aims of this study were to analyze the reported frequencies of the most relevant pharmacogenetic biomarkers and metabolic phenotypes in healthy volunteers from Mexican populations and to assess its interethnic variability across MI and MM populations. After a literature search in PubMed, and according to previously defined inclusion criteria, 63 pharmacogenetic studies performed in Mexican healthy volunteers up to date were selected. These reports comprised 56,292 healthy volunteers (71.58% MM). Allele frequencies in 31 pharmacogenetic biomarkers, from 121 searched, are described. Nine of these biomarkers presented variation within MM and MI groups. The frequencies of CYP2D6*3, *4, *5, *10, *17, *35 and *41 alleles in the MM group were different from those reported in the MI group. CYP2C9*2 and *3 alleles were more frequent in MM than in MI populations (χ2 test, p<0.05). CYP2C19*3 allele was not found in the MM or MI populations reported. For UGT1A1*28, only one study was found. HLA-A*31:01 and HLA-B*15:02 were present in some MM and MI populations. Poor metabolizers for CYP2D6 and CYP2C9 were more frequent in MM than in MI groups (χ2 test, p<0.05). Only 26% of the relevant pharmacogenetic biomarkers searched have been studied in Mexican healthy volunteers; therefore, further studies are warranted. The frequency variation of biomarkers in MM and MI populations could be important for the clinical implementation of pharmacogenetics in Mexico.

  18. Interethnic variability of pharmacogenetic biomarkers in Mexican healthy volunteers: a report from the RIBEF (Ibero-American Network of Pharmacogenetics and Pharmacogenomics).

    PubMed

    Fricke-Galindo, Ingrid; Jung-Cook, Helgi; LLerena, Adrián; López-López, Marisol

    2016-06-01

    Mexico presents a complex population diversity integrated by Mexican indigenous (MI) (7% of Mexico's population) and Mexican mestizos (MMs). This composition highlights the importance of pharmacogenetic studies in Mexican populations. The aims of this study were to analyze the reported frequencies of the most relevant pharmacogenetic biomarkers and metabolic phenotypes in healthy volunteers from Mexican populations and to assess its interethnic variability across MI and MM populations. After a literature search in PubMed, and according to previously defined inclusion criteria, 63 pharmacogenetic studies performed in Mexican healthy volunteers up to date were selected. These reports comprised 56,292 healthy volunteers (71.58% MM). Allele frequencies in 31 pharmacogenetic biomarkers, from 121 searched, are described. Nine of these biomarkers presented variation within MM and MI groups. The frequencies of CYP2D6*3, *4, *5, *10, *17, *35 and *41 alleles in the MM group were different from those reported in the MI group. CYP2C9*2 and *3 alleles were more frequent in MM than in MI populations (χ2 test, p<0.05). CYP2C19*3 allele was not found in the MM or MI populations reported. For UGT1A1*28, only one study was found. HLA-A*31:01 and HLA-B*15:02 were present in some MM and MI populations. Poor metabolizers for CYP2D6 and CYP2C9 were more frequent in MM than in MI groups (χ2 test, p<0.05). Only 26% of the relevant pharmacogenetic biomarkers searched have been studied in Mexican healthy volunteers; therefore, further studies are warranted. The frequency variation of biomarkers in MM and MI populations could be important for the clinical implementation of pharmacogenetics in Mexico. PMID:26812836

  19. Clinical toxicology study of an herbal medicinal extract of Paullinia cupana, Trichilia catigua, Ptychopetalum olacoides and Zingiber officinale (Catuama) in healthy volunteers.

    PubMed

    Oliveira, Celso H; Moraes, Maria Elizabete A; Moraes, Manoel O; Bezerra, Fernando A F; Abib, Eduardo; De Nucci, Gilberto

    2005-01-01

    In Brazil, a herbal medicinal extract named Catuama containing a mixture of Paullinia cupana (guarana; Sapindaceae), Trichilia catigua (catuaba; Meliaceae), Ptychopetalum olacoides (muirapuama; Olacaceae) and Zingiber officinale (ginger; Zingiberaceae) is used as a body stimulant, energetic, tonic and aphrodisiac. The present study investigated the chronic administration of 25 mL Catuama twice a day during 28 days for any toxic effect on healthy human volunteers of both sexes. No severe adverse reactions or haematological and biochemical changes were reported.

  20. Blood pressure lowering effect of Nigella sativa L. seed oil in healthy volunteers: a randomized, double-blind, placebo-controlled clinical trial.

    PubMed

    Fallah Huseini, H; Amini, M; Mohtashami, R; Ghamarchehre, M E; Sadeqhi, Z; Kianbakht, S; Fallah Huseini, A

    2013-12-01

    Nigella sativa L. seeds (N. sativa) have been used as a traditional remedy for a wide range of diseases including hypertension. The present study was performed to explore the effects of N. sativa oil on blood pressure (BP) in healthy volunteers. In a double-blind, randomized study, 70 healthy volunteers aged 34 to 63 years with systolic BP from 110 to 140 mmHg and diastolic BP from 60 to 90 mmHg were randomly allocated to receive 2.5 mL N. sativa oil or placebo two times a day for 8 weeks. The systolic and diastolic BPs, body mass index and blood levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, creatinine and blood urea nitrogen were determined at baseline and endpoint. Results showed that in N. sativa oil treated group the systolic and diastolic BPs decreased significantly compared with baseline and placebo group at the endpoint. Other parameters did not significantly change in both groups at the endpoint. No adverse effects were reported. In conclusion, oral daily administration of 5 mL N. sativa oil to healthy volunteers for 8 weeks lowers systolic and diastolic BPs without any adverse effects.

  1. Comparison of antiplatelet activity of garlic tablets with cardio-protective dose of aspirin in healthy volunteers: a randomized clinical trial

    PubMed Central

    Shafiekhani, Mojtaba; Faridi, Pouya; Kojuri, Javad; Namazi, Soha

    2016-01-01

    Objective: Some of the adverse effects of aspirin including peptic ulcers, gastrointestinal bleeding and aspirin resistance compelled researchers to find a suitable alternative with fewer adverse effects. In this clinical trial, we aimed to find the effective antiplatelet dose of garlic. Materials and Methods: This randomized controlled clinical trial (RCT) was conducted on 62 healthy volunteers of 20-50 years old. All volunteers used 80 mg aspirin per day for 1 week and at the end of this time, platelet aggregation (PA) induced by 4 agonists acting in aggregation pathway including adenosinediphosphate (20 μmol/l), epinephrine (20 μmol/l), collagen(0.19 mg/ ml) and arachidonic acid (0.5mg/ ml) was measured by Light Transmittance Aggregometry (LTA) in all participants. After one month washout period, volunteers were randomized into 3 groups and each received 1, 2 or 3 garlic tablets (1250 mg) a day for 1 month. After one month, PA was examined in all groups. Results: The mean ±SD of the age of all volunteers was 28.60 ± 9.00 years. In addition, 52.00 % of our volunteers were male and 48.00% of them were female. Garlic tablet didnot have significant effect on PA at any dose. However, 30% of volunteers in the group that used 3 garlic tablets/day reported adverse effect (i.e. bleeding). No significant association between sex, age and PA was observed. Conclusion: In this study, we were unable to determine the effective anti-platelet dose of garlic which that could be equal to that of aspirin anti-platelet activity, as assessed LTA method. PMID:27761425

  2. The effects of moclobemide on the pharmacokinetics of the 5-HT1B/1D agonist rizatriptan in healthy volunteers

    PubMed Central

    van Haarst, A D; van Gerven, J M A; Cohen, A F; De Smet, M; Sterrett, A; Birk, K L; Fisher, A L; De Puy, M E; Goldberg, M R; Musson, D G

    1999-01-01

    Aims The new 5-HT1B/1D agonist rizatriptan (MK-0462) has recently been registered for the treatment of migraine. Its primary route of metabolism is via monoamine oxidase-A (MAO-A). Antidepressants such as the MAO-A inhibitor moclobemide may be used in patients with chronic headache syndromes. Hence, this study aimed to investigate the interactions between rizatriptan and moclobemide. Methods In a double-blind, randomized, placebo-controlled, two-period cross-over study 12 healthy, young volunteers (six males, six females) were treated with moclobemide (150 mg twice daily) or placebo for 4 days. On the fourth day, a single dose of rizatriptan (10 mg) was administered, and subsequently blood and urine samples were collected for assay of rizatripan and N-monodesmethyl rizatriptan. Plasma concentrates of 3,4-dihydroxyphenylglycol (DHPG), a marker of MAO-A inhibition, were also assessed. Supine and standing blood pressure were measured regularly. Results Both treatments were well tolerated. During moclobemide, the increase in supine diastolic blood pressure following rizatriptan administration was augmented. Inhibition of MAO by moclobemide was inferred from a persistent decrease in DHPG level (43% on average). When rizatriptan was coadministered with moclobemide, the area under the plasma drug concentration-time profiles for rizatriptan and its N-monodesmethyl metabolite increased 2.2-fold (90% CI, 1.93–2.47) and 5.3-fold (90% CI, 4.81–5.91), respectively, when compared with placebo. Peak plasma drug concentrations for rizatriptan and its n-monodesmethyl metabolite increased 1.4-fold (90% CI, 1.11–1.80) and 2.6-fold (90% CI, 2.23–3.14), respectively, and half-lives of both were prolonged. Conclusions Moclobemide inhibited the metabolism of rizatriptan and its active N-monodesmethyl metabolite through inhibition of MAO-A. Thus, moclobemide may considerably potentiate rizatriptan action. Concurrent administration of moclobemide and rizatriptan is not recommended

  3. Effects of food and alcohol on the pharmacokinetics of an oral, extended-release formulation of hydrocodone in healthy volunteers

    PubMed Central

    Farr, Stephen J; Robinson, Cynthia Y; Rubino, Christopher M

    2015-01-01

    Background The purpose of this study was to evaluate the pharmacokinetics, bioavailability, and safety of oral extended-release hydrocodone (HC-ER) when administered with food or alcohol. Methods Two single-center, open-label, randomized, crossover studies were conducted in healthy volunteers. In a two-period food-interaction study, 12 subjects received HC-ER 20 mg after an overnight fast and a high-fat meal. In a three-period alcohol-interaction study, 30 naltrexone-blocked subjects received HC-ER 50 mg with a 0%, 20%, or 40% alcohol/orange juice solution after an overnight fast. Pharmacokinetic parameters were derived from plasma concentrations of hydrocodone and its metabolites. Results Exposure to hydrocodone after HC-ER 20 mg was similar in the fed and fasted states, as assessed by area under the plasma concentration versus time curve from time of dosing to time of last detectable concentration (AUC0–t; 316.14 versus 311.94 ng · h/mL); relative bioavailability (Frel) was 101.74%. Differences (fed versus fasted) in hydrocodone mean maximum plasma concentration (Cmax; 28.86 versus 22.74 ng/mL) and median time to Cmax (tmax; 6 versus 8 hours) were not clinically significant. Administration of 20% alcohol with HC-ER 50 mg did not increase systemic exposure relative to 0% alcohol (AUC0–t 878 versus 832 ng · h/mL; Frel 105%) or result in clinically meaningful changes in Cmax (51.8 versus 46.3 ng/mL) or tmax (5.44 versus 6.16 hours). Administration with 40% alcohol increased AUC0–t (1,008 ng · h/mL versus 832 ng · h/mL; Frel 120%) and Cmax (109 versus 46.3 ng/mL), and shortened tmax (2.43 versus 6.16 hours). Adverse events occurred in 10.0%, 24.1%, and 66.7% of subjects after 0%, 20%, and 40% alcohol, respectively. Conclusion HC-ER can be administered without regard to meals. While there was no evidence of “dose-dumping” (an unintended, rapid release in a short time period of all or most of the hydrocodone from HC-ER), even with 40% alcohol, as with all

  4. A low TSH profile predicts olanzapine-induced weight gain and relief by adjunctive topiramate in healthy male volunteers.

    PubMed

    Evers, Simon S; van Vliet, André; van Vugt, Barbara; Scheurink, Anton J W; van Dijk, Gertjan

    2016-04-01

    Second generation antipsychotics, like olanzapine (OLZ), have become the first line drug treatment for patients with schizophrenia. However, OLZ treatment is often associated with body weight (BW) gain and metabolic derangements. Therefore, the search for prospective markers for OLZ's negative side effects as well as adjunctive treatments to inhibit these has been of major interest. The aim of this study was to investigate in healthy male volunteers (age: 36 ± 11 years; BW: 84 ± 12 kg; BMI=25.5 ± 2.5) whether adjunctive topiramate (TPM) administration opposes OLZ-induced weight gain over the course of 14 days treatment. In addition, we investigated behavioral, endocrine and metabolic characteristics as underlying and potentially predictive factors for weight regulation and/or metabolic derangements associated with OLZ and TPM treatment. While adjunctive TPM indeed reduced OLZ-induced weight gain (P<0.05, Mann-Whitney U), behavioral/metabolic/endocrine characteristics of OLZ treatment were not affected by TPM. Using multiple regression analysis, BW gain was the key factor explaining metabolic disturbances (e.g., plasma insulin- LDL interaction: P<0.01, R(2)=.320), and cumulative food intake during treatment was the best denominator of BW gain (P<0.01, R(2)=.534). Neither TPM treatment, nor its circulating levels, contributed to variation observed in ΔBW. In a second multiple regression analysis, we observed that a low baseline thyrotropin profile (TSHAUC) before the start of drug treatment was associated with an increase in ΔBW over the course of drug treatment (P<0.05, R(2)=.195). Adding TSHAUC as covariate revealed that adjunctive TPM treatment did attenuate OLZ induced BW gain (P<0.05, ANCOVA). Further exploration of the circulating thyroid hormones revealed that individuals with a low plasma TSH profile were also those that were most sensitive to adjunctive TPM treatment blocking OLZ-induced ΔBW gain. Others have shown that OLZ-induced BW gain is

  5. A low TSH profile predicts olanzapine-induced weight gain and relief by adjunctive topiramate in healthy male volunteers.

    PubMed

    Evers, Simon S; van Vliet, André; van Vugt, Barbara; Scheurink, Anton J W; van Dijk, Gertjan

    2016-04-01

    Second generation antipsychotics, like olanzapine (OLZ), have become the first line drug treatment for patients with schizophrenia. However, OLZ treatment is often associated with body weight (BW) gain and metabolic derangements. Therefore, the search for prospective markers for OLZ's negative side effects as well as adjunctive treatments to inhibit these has been of major interest. The aim of this study was to investigate in healthy male volunteers (age: 36 ± 11 years; BW: 84 ± 12 kg; BMI=25.5 ± 2.5) whether adjunctive topiramate (TPM) administration opposes OLZ-induced weight gain over the course of 14 days treatment. In addition, we investigated behavioral, endocrine and metabolic characteristics as underlying and potentially predictive factors for weight regulation and/or metabolic derangements associated with OLZ and TPM treatment. While adjunctive TPM indeed reduced OLZ-induced weight gain (P<0.05, Mann-Whitney U), behavioral/metabolic/endocrine characteristics of OLZ treatment were not affected by TPM. Using multiple regression analysis, BW gain was the key factor explaining metabolic disturbances (e.g., plasma insulin- LDL interaction: P<0.01, R(2)=.320), and cumulative food intake during treatment was the best denominator of BW gain (P<0.01, R(2)=.534). Neither TPM treatment, nor its circulating levels, contributed to variation observed in ΔBW. In a second multiple regression analysis, we observed that a low baseline thyrotropin profile (TSHAUC) before the start of drug treatment was associated with an increase in ΔBW over the course of drug treatment (P<0.05, R(2)=.195). Adding TSHAUC as covariate revealed that adjunctive TPM treatment did attenuate OLZ induced BW gain (P<0.05, ANCOVA). Further exploration of the circulating thyroid hormones revealed that individuals with a low plasma TSH profile were also those that were most sensitive to adjunctive TPM treatment blocking OLZ-induced ΔBW gain. Others have shown that OLZ-induced BW gain is

  6. A prospective assessment of sacral pressures in healthy volunteers seated upright and reclined with legs elevated in a recliner.

    PubMed

    Miller, Stephannie K; Aberegg, Lauren; Blasiole, Kimberly; Parker, Michael; Fulton, Judith

    2014-09-01

    Prolonged, unrelieved pressure is a major risk factor for pressure ulceration, and interface tissue pressures have been shown to be very high when a person is sitting. Using convenience sampling methods, 23 healthy participants (four men, 19 women, mean age 45 years, body mass index [BMI] range 20-45) participated in a prospective pilot study to evaluate the effect of BMI and two commonly used seating positions in standard hospital reclining chairs on tissue (especially sacral) interface pressures. Measurements were obtained when volunteers were seated upright with plantar surfaces of feet touching the floor (Position 1) and reclining with legs resting on an elevated surface (Position 2). Measurements were obtained for 6 minutes using a thin, flexible force sensing array 430-mm x 430-mm seat mat. Average pressure, maximum pressure, and the number of sensors reading >60 mm Hg and >80 mm Hg were used for analysis across the total surface and at the sacrum. Participants were categorized by BMI (category 1: 20-22, category 2: 23-28, category 3: 29+; no participants had a BMI <20). Leg elevation reduced average pressure across the total surface (from 42.9 mm Hg to 40.0 mm Hg, P = 0.015) and the number of sensors reading >60 mm Hg at the sacrum (from 31.4 to 27.1, P = 0.047). BMI and position were significantly correlated with the number of sensors reading >80 mm Hg (P = 0.008) and average pressure (P = 0.031). Pairwise comparisons showed significant differences existed between BMI categories 1 (average delta: -3.63, indicating down position is better) and 3 (average delta: 4.67, indicating up position is better) for the difference in number of sensors above 80 mm Hg (P = 0.030). Research is needed to further explore the relationship between BMI and tissue pressure, but the results of this study suggest that for patients with a BMI >29, elevating the heels/reclining the chair significantly reduces sacral tissue interface pressure. Further research specific to pressure

  7. LC-MS Method for Studying the Pharmacokinetics and Bioequivalence of Clonidine Hydrochloride in Healthy Male Volunteers

    PubMed Central

    Danafar, Hossein; Hamidi, Mehrdad

    2016-01-01

    Background: A simple and sensitive high performance liquid chromatography-electrospray ionization mass spectrometry method has been evaluated for the assignment of clonidine hydrochloride in human plasma. Methods: The mobile phase composed of acetonitrile-water 60:40 (v/v) and 0.2% formic acid 20 μl of sample was chromatographically analyzed using a repacked ZORBAX-XDB-ODS C18 column (2.1 mm×30 mm, 3.5 μ). Detection of analytes was achieved by tandem mass spectrometry with Electrospray Ionization (ESI) interface in positive ion mode operated under the multiple-reaction monitoring mode (m/z 230.0 →213). Sample pretreatment consisted of a one-step Protein Precipitation (PPT) with methanol and perchloric acid (HClO4) of 0.10 ml plasma. Results: Standard curve was linear (r=0.998) over the concentration range of 0.01–10.0 ng/ml and showed suitable accuracy and precision. The Limit of Quantification (LOQ) was 0.01 ng/ml. The mean (SD) Cmax, Tmax, AUC0–t and AUC0–∞ values after administration of the test and reference formulations, respectively, were in this manner: 6.16 (0.32) versus 6.21 (0.07) ng/ml, 30.12 (0.86) versus 30.13 (0.73) hr, 290.37 (1.13) versus 293.39 (1.22) ng/ml/hr, and 350.17 (1.98) versus 352.96 (1.67) ng/ml/hr. The mean (SD) t1/2 was 120.12 (1.90) hr for the test formulation and 120.96 (1.54) hr for the reference formulation. No statistical differences were showed for Cmax and the area under the plasma concentration-time curve for test and reference tablets. Conclusion: The method is rapid, simple, very steady and precise for the separation, assignment, pharmacokinetic and bioavailability evaluation of clonidine in healthy Iranian adult male volunteers. PMID:27141268

  8. A prospective assessment of sacral pressures in healthy volunteers seated upright and reclined with legs elevated in a recliner.

    PubMed

    Miller, Stephannie K; Aberegg, Lauren; Blasiole, Kimberly; Parker, Michael; Fulton, Judith

    2014-09-01

    Prolonged, unrelieved pressure is a major risk factor for pressure ulceration, and interface tissue pressures have been shown to be very high when a person is sitting. Using convenience sampling methods, 23 healthy participants (four men, 19 women, mean age 45 years, body mass index [BMI] range 20-45) participated in a prospective pilot study to evaluate the effect of BMI and two commonly used seating positions in standard hospital reclining chairs on tissue (especially sacral) interface pressures. Measurements were obtained when volunteers were seated upright with plantar surfaces of feet touching the floor (Position 1) and reclining with legs resting on an elevated surface (Position 2). Measurements were obtained for 6 minutes using a thin, flexible force sensing array 430-mm x 430-mm seat mat. Average pressure, maximum pressure, and the number of sensors reading >60 mm Hg and >80 mm Hg were used for analysis across the total surface and at the sacrum. Participants were categorized by BMI (category 1: 20-22, category 2: 23-28, category 3: 29+; no participants had a BMI <20). Leg elevation reduced average pressure across the total surface (from 42.9 mm Hg to 40.0 mm Hg, P = 0.015) and the number of sensors reading >60 mm Hg at the sacrum (from 31.4 to 27.1, P = 0.047). BMI and position were significantly correlated with the number of sensors reading >80 mm Hg (P = 0.008) and average pressure (P = 0.031). Pairwise comparisons showed significant differences existed between BMI categories 1 (average delta: -3.63, indicating down position is better) and 3 (average delta: 4.67, indicating up position is better) for the difference in number of sensors above 80 mm Hg (P = 0.030). Research is needed to further explore the relationship between BMI and tissue pressure, but the results of this study suggest that for patients with a BMI >29, elevating the heels/reclining the chair significantly reduces sacral tissue interface pressure. Further research specific to pressure

  9. Towards Deeper Research and Better Policy for Healthy Aging --Using the Unique Data of Chinese Longitudinal Healthy Longevity Survey1

    PubMed Central

    Zeng, Yi

    2014-01-01

    The objectives of this review article are to facilitate deeper research and better policy analysis for healthy aging, which not only means surviving to old ages in good health, but also mean the economics and society of our country would be aging healthily, with sound policy and intervention programs. Toward these objectives, we introduce the Chinese Longitudinal Healthy Longevity Survey (CLHLS), which has been conducted by Center for Healthy Aging and Development Studies, National School of Development of Peking University since 1998. We present a comprehensive and summarized introduction of the CLHLS study design, sample distributions, contents, general quality assessment and availability of the CLHLS data collected. Such an introduction would be helpful for our colleagues who may be interested in using this unique and more-than-fourteen-year longitudinal survey data resource for deeper interdisciplinary research and better policy analysis on healthy aging. To illustrate how the unique data resources of CLHLS may be useful, we also summarize and discuss ten selected healthy aging policy related research based on data from the CLHLS. Finally, we discussed the future perspectives using the unique and rich CLHLS datasets. PMID:24443653

  10. Intranasal Human Growth Hormone (hGH) Induces IGF-1 Levels Comparable With Subcutaneous Injection With Lower Systemic Exposure to hGH in Healthy Volunteers

    PubMed Central

    Lewis, Andrew L.; Patel, Tina; Jeffery, Kirk; King, Gareth; Savage, Martin; Shalet, Stephen; Illum, Lisbeth

    2015-01-01

    Context: The development of an improved, efficacious human GH (hGH) product administered by a noninjectable route of delivery such as the nasal route is highly desirable. We have developed a novel nasal hGH product (CP024) that showed excellent nasal absorption in animal models; however, the translation of these results into the clinical setting is essential because past attempts to develop such formulations by other groups have been unable to induce IGF-1 in man. Objective: The objective of the study was to assess the pharmacokinetics, pharmacodynamics, and tolerability of CP024 compared with a sc hGH injection. Design: This was a single-center, nonrandomized placebo-controlled, open-label, five-way crossover study in eight healthy volunteers. Setting: The study was carried out at a contract research organization, Quotient Bioresearch. Volunteers: Eight healthy male volunteers, given an iv infusion of octreotide to suppress the endogenous GH secretion during the study period, participated in the study. No volunteers were withdrawn due to side effects. Main Outcome Measures: Measurement of hGH and IGF-1 levels and tolerability of the drug product was performed. Results: No serious adverse events were reported and no subjects withdrawn from study due to the treatment. After the nasal administration of CP024, 3-fold higher hGH blood levels were obtained as compared with hGH nasal control. The relative bioavailability was about 3%. CP024 (given twice daily) induced a significant increase in IGF-1 levels up to 19 hours after administration, with no significant difference to those obtained after the sc injection of hGH. Conclusions: The study indicates that CP024 is a promising candidate for an efficacious nasal product for the treatment of GH deficiency due to induction of IGF-1 similar to that after a sc injection, despite the lower plasma hGH concentration obtained. A dose-response study is needed to evaluate the optimal nasal dose. PMID:26425883

  11. Moving in an Environment of Induced Sensorimotor Incongruence Does Not Influence Pain Sensitivity in Healthy Volunteers: A Randomised Within-Subject Experiment

    PubMed Central

    Wand, Benedict Martin; Szpak, Lareina; George, Pamela J.; Bulsara, Max K.; O’Connell, Neil Edward; Moseley, G. Lorimer

    2014-01-01

    Objectives It has been proposed that in the same way that conflict between vestibular and visual inputs leads to motion sickness, conflict between motor commands and sensory information associated with these commands may contribute to some chronic pain states. Attempts to test this hypothesis by artificially inducing a state of sensorimotor incongruence and assessing self-reported pain have yielded equivocal results. To help clarify the effect sensorimotor incongruence has on pain we investigated the effect of moving in an environment of induced incongruence on pressure pain thresholds (PPT) and the pain experienced immediately on completion of PPT testing. Methods Thirty-five healthy subjects performed synchronous and asynchronous upper-limb movements with and without mirror visual feedback in random order. We measured PPT over the elbow and the pain evoked by testing. Generalised linear mixed-models were performed for each outcome. Condition (four levels) and baseline values for each outcome were within-subject factors. Results There was no effect of condition on PPT (p = 0.887) or pressure-evoked pain (p = 0.771). A sensitivity analysis using only the first PPT measure after each condition confirmed the result (p = 0.867). Discussion Inducing a state of movement related sensorimotor incongruence in the upper-limb of healthy volunteers does not influence PPT, nor the pain evoked by testing. We found no evidence that sensorimotor incongruence upregulates the nociceptive system in healthy volunteers. PMID:24709995

  12. Pharmacokinetics of ceftazidime in serum and suction blister fluid during continuous and intermittent infusions in healthy volunteers.

    PubMed Central

    Mouton, J W; Horrevorts, A M; Mulder, P G; Prens, E P; Michel, M F

    1990-01-01

    The pharmacokinetics of ceftazidime were investigated during intermittent (II) and continuous (CI) infusion in eight healthy male volunteers in a crossover fashion. The total daily dose was 75 mg/kg of body weight per 24 h in both regimens, given in three doses of 25 mg/kg/8 h (II) or 60 mg/kg/24 h with 15 mg/kg as a loading dose (CI). After the third dose (II) and during CI, serum and blister fluid samples were taken. Seven new blisters were raised for each timed sample by a suction blister technique. Blisters took 90 min to form. Samples were then taken from four blisters (A samples) and 1 h later were taken from the remaining three (B samples). The concentration of ceftazidime was determined using a high-performance liquid chromatography method. After II, the concentrations in serum immediately after infusion (t = 30 min) and 8 h after the start of the infusion were 137.9 (standard deviation [SD], 27.5) and 4.0 (SD, 0.7) micrograms/ml, respectively. The half-life at alpha phase (t1/2 alpha) was 9.6 min (SD, 4.6), t1/2 beta was 94.8 min (SD, 5.4), area under the concentration-time curve (AUC) was 285.4 micrograms.h/ml (SD, 22.7), total body clearance was 0.115 liter/h.kg (SD, 0.022), and volume of distribution at steady state was 0.178 liter/kg (SD, 0.023). The blister fluid (A) samples showed a decline in concentration parallel to that of the concentrations in serum during the elimination phase with a ratio of 1:1. The t1/2 of the A samples was 96.4 min (SD, 3.2). The concentration of ceftazidime in the B blister fluid samples was significantly higher (27%) than in the A samples over time. This shows that blisters may behave as a separate compartment and establishes the need to raise new blisters for each timed sample. The mean AUC/h during continuous infusion was 21.3 micrograms . h/ml (SD, 3.0). The total body clearance was 0.113 liter/h . kg (SD, 0.018), the urinary clearance was 0.105 liter/h . kg (SD, 0.012), and the ceftazidime/creatinine clearance ratio

  13. Silent period to transcranial magnetic stimulation: construction and properties of stimulus-response curves in healthy volunteers.

    PubMed

    Kimiskidis, V K; Papagiannopoulos, S; Sotirakoglou, K; Kazis, D A; Kazis, A; Mills, K R

    2005-05-01

    Silent period (SP) is widely used in transcranial magnetic stimulation studies. Methodologically, SP is usually elicited at stimulus intensities corresponding to a certain percentage of corticomotor threshold. Because this approach might lead to factitious SP changes, the present study was designed to develop, in a stepwise manner, a method for investigating SP independently of corticomotor threshold. First, stimulus-response (S-R) curves of SP against stimulus intensity (SI) were constructed and quantitatively described in healthy volunteers. Second, various methodological issues such as the optimum model for describing the relationship between SP duration and SI and the importance of the type of stimulating coil were addressed. Finally, the proposed method and a commonly used method (eliciting SPs at 130% MT SI) were directly compared for a group of epileptic patients for whom administration of oxcarbazepine resulted in significant corticomotor threshold elevation. Twenty-one subjects (eleven females, median age, 38 years) were studied. SPs were obtained with a figure-of-eight coil using a standardized procedure (recording, FDI). Pilot experiments indicated that at least four trials were required, at each intensity level, to estimate the mean SP duration within 10% of the true mean. Therefore, SPs were determined from the average of four trials with 5% increments from 5 to 100% maximum SI. In a second set of experiments, SPs were obtained for fifteen subjects using a circular coil. In a third set of experiments, eight epileptic patients were studied before and after administration of oxcarbazepine (mean dose 1553 mg, range 900-1800 mg). The S-R curves were fitted to a Boltzman function and to first-order to fourth-order polynomial and sigmoid functions. The Boltzman function described the data accurately (R2=0.947-0.990). In addition, direct comparison of the six models with an F-test proved the superiority of the first. The best-fit parameters of the reference

  14. Topographic pharmaco-EEG mapping of the effects of the South American psychoactive beverage ayahuasca in healthy volunteers

    PubMed Central

    Riba, Jordi; Anderer, Peter; Morte, Adelaida; Urbano, Gloria; Jané, Francesc; Saletu, Bernd; Barbanoj, Manel J

    2002-01-01

    Aims Ayahuasca is a traditional South American psychoactive beverage used in Amazonian shamanism, and in the religious ceremonies of Brazilian-based syncretic religious groups with followers in the US and several European countries. This tea contains measurable amounts of the psychotropic indole N,N-dimethyltryptamine (DMT), and β-carboline alkaloids with MAO-inhibiting properties. In a previous report we described a profile of stimulant and psychedelic effects for ayahuasca as measured by subjective report self-assessment instruments. In the present study the cerebral bioavailability and time-course of effects of ayahuasca were assessed in humans by means of topographic quantitative-electroencephalography (q-EEG), a noninvasive method measuring drug-induced variations in brain electrical activity. Methods Two doses (one low and one high) of encapsulated freeze-dried ayahuasca, equivalent to 0.6 and 0.85 mg DMT kg−1 body weight, were administered to 18 healthy volunteers with previous experience in psychedelic drug use in a double-blind crossover placebo-controlled clinical trial. Nineteen-lead recordings were undertaken from baseline to 8 h after administration. Subjective effects were measured by means of the Hallucinogen Rating Scale (HRS). Results Ayahuasca induced a pattern of psychoactive effects which resulted in significant dose-dependent increases in all subscales of the HRS, and in significant and dose-dependent modifications of brain electrical activity. Absolute power decreased in all frequency bands, most prominently in the theta band. Mean absolute power decreases (95% CI) at a representative lead (P3) 90 min after the high dose were −20.20±15.23 µV2 and −2.70±2.21 µV2 for total power and theta power, respectively. Relative power decreased in the delta (−1.20±1.31% after 120 min at P3) and theta (−3.30±2.59% after 120 min at P3) bands, and increased in the beta band, most prominently in the faster beta-3 (1.00±0.88% after 90 min at P

  15. Urinary bactericidal activity and pharmacokinetics of enoxacin versus norfloxacin and ciprofloxacin in healthy volunteers after a single oral dose.

    PubMed

    Well, M; Naber, K G; Kinzig-Schippers, M; Sörgel, F

    1998-04-01

    In an open, randomised monocentric crossover study in six male and six female healthy volunteers, the urinary antibacterial activity and pharmacokinetics of enoxacin, norfloxacin and ciprofloxacin were assessed. Urine was collected up to 6 days, and venous blood samples up to 12 h, after a single oral dose of 400 mg enoxacin, 400 mg norfloxacin and 500 mg ciprofloxacin. Enoxacin (250 mg/l) demonstrated the highest peak concentration (median) in the urine (0-6 h), followed by ciprofloxacin (237 mg/l) and norfloxacin (157 mg/l) as determined by the HPLC assay. The total amount (mean) excreted by the kidneys as parent drugs were as follows: enoxacin 54% of dose, ciprofloxacin 33% of dose, and norfloxacin 22% of dose. The mean plasma concentrations decreased from 1 to 4 h after administration for enoxacin from 1.9 to 1.4 mg/l, for ciprofloxacin from 2.0 to 0.8 mg/l and for norfloxacin from 1.3 to 0.5 mg/l. The antibacterial activity in urine was determined as urinary bactericidal titers (UBT), i.e. the highest 2-fold dilution of urine still bactericidal for the reference organism (E. coli ATCC 25,922) and for five uropathogens with minimal inhibitory (MIC) and bactericidal (MBC) concentrations ranging from highly susceptible to resistant cultured from the urine of patients with complicated urinary tract infections (UTI). For the E. coli ATCC 25,922, the organism with the lowest MIC, median UBTs of ciprofloxacin were present for 4 days, decreasing from 1:512 to 1:2, that of enoxacin for 2 days, decreasing from 1:256 to 1:4, and that of norfloxacin for 2 days, decreasing from 1:128 to 1:2. For the five uropathogens (with increasing MICs: K. pneumoniae, P. mirabilis, E. coli (resistant to nalidixic acid), P. aeruginosa and E. faecalis), the UBTs decreased in general, according to MICs, demonstrating the same relations of UBTs for ciprofloxacin (highest) versus enoxacin (medium) versus norfloxacin (lowest) with one exception (P. mirabilis) for which norfloxacin showed

  16. Application of intermittent negative pressure on the lower extremity and its effect on macro- and microcirculation in the foot of healthy volunteers.

    PubMed

    Sundby, Øyvind H; Høiseth, Lars Øivind; Mathiesen, Iacob; Jørgensen, Jørgen J; Weedon-Fekjær, Harald; Hisdal, Jonny

    2016-09-01

    Intermittent negative pressure (INP) applied to the lower leg and foot may increase peripheral circulation. However, it is not clear how different patterns of INP affect macro- and microcirculation in the foot. The aim of this study was therefore to determine the effect of different patterns of negative pressure on foot perfusion in healthy volunteers. We hypothesized that short periods with INP would elicit an increase in foot perfusion compared to no negative pressure. In 23 healthy volunteers, we continuously recorded blood flow velocity in a distal foot artery, skin blood flow, heart rate, and blood pressure during application of different patterns of negative pressure (-40 mmHg) to the lower leg. Each participant had their right leg inside an airtight chamber connected to an INP generator. After a baseline period at atmospheric pressure, we applied four different 120 sec sequences with either constant negative pressure or different INP patterns, in a randomized order. The results showed corresponding fluctuations in blood flow velocity and skin blood flow throughout the INP sequences. Blood flow velocity reached a maximum at 4 sec after the onset of negative pressure (average 44% increase above baseline, P < 0.001). Skin blood flow and skin temperature increased during all INP sequences (P < 0.001). During constant negative pressure, average blood flow velocity, skin blood flow, and skin temperature decreased (P < 0.001). In conclusion, we observed increased foot perfusion in healthy volunteers after the application of INP on the lower limb.

  17. Engaging Stakeholders From Volunteer-Led Out-of-School Time Programs in the Dissemination of Guiding Principles for Healthy Snacking and Physical Activity

    PubMed Central

    Koomas, Alyssa; Metayer, Nesly; Fullerton, Karen J.; Hubbard, Kristie L.; Anzman-Frasca, Stephanie; Hofer, Teresa; Nelson, Miriam; Newman, Molly; Sacheck, Jennifer; Economos, Christina

    2015-01-01

    Background Little effort has focused on the role of volunteer-led out-of-school time (OST) programs (ie, enrichment and sports programs) as key environments for the promotion of healthy eating and physical activity habits among school-aged children. The Healthy Kids Out of School (HKOS) initiative developed evidence-based, practical guiding principles for healthy snacks, beverages, and physical activity. The goal of this case study was to describe the methods used to engage regional partners to understand how successful implementation and dissemination of these principles could be accomplished. Community Context HKOS partnered with volunteer-led programs from 5 OST organizations in Maine, Massachusetts, and New Hampshire to create a regional “learning laboratory.” Methods We engaged partners in phases. In the first phase, we conducted focus groups with local volunteer program leaders; during the second phase, we held roundtable meetings with regional and state program administrators; and in the final phase, we conducted additional outreach to refine and finalize implementation strategies. Outcomes Implementation strategies were developed based on themes and information that emerged. For enrichment programs, strategies included new patch and pin programs that were consistent with the organizations’ infrastructure and usual practices. For sports programs, the main strategy was integration with online trainings for coaches. Interpretation Through the engagement process, we learned that dissemination of the guiding principles in these large and complex OST organizations was best accomplished by using implementation strategies that were customized, integrated, and aligned with goals and usual practices. The lessons learned can benefit future efforts to prevent obesity in complex environments. PMID:26704443

  18. Effect of DA-9701 on Gastric Motor Function Assessed by Magnetic Resonance Imaging in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Min, Yang Won; Min, Byung-Hoon; Kim, Seonwoo; Choi, Dongil; Rhee, Poong-Lyul

    2015-01-01

    Background Improving gastric accommodation and gastric emptying is an attractive physiological treatment target in patients with functional dyspepsia (FD). We evaluated the effect of DA-9701, a new drug for FD, on gastric motor function after a meal in healthy volunteers using magnetic resonance imaging (MRI). Methods Forty healthy volunteers were randomly allocated to receive either DA-9701 or placebo. After 5 days of treatment, subjects underwent gastric MRI (60 min before and 15, 30, 45, 60, 90, and 120 min after a liquid test meal). Gastric volume was measured through 3-dimensional reconstruction from MRI data. We analyzed 4 outcome variables including changes in total gastric volume (TGV), proximal TGV, and proximal to distal TGV ratio after a meal and gastric emptying rates after adjusting values at the pre-test meal. Results Changes in TGV and proximal TGV after a meal did not differ between the DA-9701 and placebo groups (difference between groups -25.9 mL, 95% confidence interval [CI] -54.0 to 2.3 mL, P = 0.070 and -2.9 mL, 95% CI -30.3 to 24.5 mL, P = 0.832, respectively). However, pre-treatment with DA-9701 increased postprandial proximal to distal TGV ratio more than placebo (difference between groups 0.93, 95% CI 0.08 to 1.79, P = 0.034). In addition, pre-treatment with DA-9701 significantly increased gastric emptying as compared with placebo (mean difference between groups 3.41%, 95% CI 0.54% to 6.29%, P = 0.021, by mixed model for repeated measures). Conclusion Our results suggested that DA-9701 enhances gastric emptying and does not significantly affect gastric accommodation in healthy volunteers. Further studies to confirm whether DA-9701 enhances these gastric motor functions in patients with FD are warranted. Trial Registration ClinicalTrials.gov NCT02091635 PMID:26402448

  19. A Chronological Increase in Gastric Acid Secretion from 1995 to 2014 in Young Japanese Healthy Volunteers under the Age of 40 Years Old.

    PubMed

    Iijima, Katsunori; Koike, Tomoyuki; Abe, Yasuhiko; Ohara, Shuichi; Shimosegawa, Tooru

    2016-01-01

    Gastric acid secretion levels are an important determinant of the manifestation of acid-related upper GI diseases such as gastroesophageal reflux disease. We recently reported that gastric acid secretion levels did not change from the 1990s to 2010s in H. pylori-negative asymptomatic Japanese outpatients with a mean age of 63 years old. However, because young people have a quite different lifestyle, including dietary pattern, from elderly people in Japan, it is worth investigating any chronologic changes in gastric acid secretion in younger generations. The aim of this analysis is to investigate the potential changes in gastric acid secretion from 1995 to 2014 in young Japanese healthy volunteers. Eighty-eight young Japanese healthy volunteers under the age of 40 with a mean age of 26 were extracted from a database accumulated from 1995 to 2014 for the present analysis. Their gastrin-stimulated gastric acid level was determined with the endoscopic gastrin test. In 76 H. pylori-negative subjects, gastric acid secretion levels showed a significant positive correlation with the calendar year when the test was performed (r = 0.27, p < 0.01). A similar trend was observed in 12 H. pylori-positive subjects. A chronological 5-year time period showed a significant positive association with gastric acid secretion in univariate and multivariate analyses (p < 0.01 and p = 0.01, respectively). Gastric acid secretion levels have been increasing in young Japanese healthy volunteers during the last 20 years. We need to monitor future trends in the prevalence of acid-related diseases such as gastro-esophageal reflux disease in Japan. PMID:27440759

  20. Application of intermittent negative pressure on the lower extremity and its effect on macro- and microcirculation in the foot of healthy volunteers.

    PubMed

    Sundby, Øyvind H; Høiseth, Lars Øivind; Mathiesen, Iacob; Jørgensen, Jørgen J; Weedon-Fekjær, Harald; Hisdal, Jonny

    2016-09-01

    Intermittent negative pressure (INP) applied to the lower leg and foot may increase peripheral circulation. However, it is not clear how different patterns of INP affect macro- and microcirculation in the foot. The aim of this study was therefore to determine the effect of different patterns of negative pressure on foot perfusion in healthy volunteers. We hypothesized that short periods with INP would elicit an increase in foot perfusion compared to no negative pressure. In 23 healthy volunteers, we continuously recorded blood flow velocity in a distal foot artery, skin blood flow, heart rate, and blood pressure during application of different patterns of negative pressure (-40 mmHg) to the lower leg. Each participant had their right leg inside an airtight chamber connected to an INP generator. After a baseline period at atmospheric pressure, we applied four different 120 sec sequences with either constant negative pressure or different INP patterns, in a randomized order. The results showed corresponding fluctuations in blood flow velocity and skin blood flow throughout the INP sequences. Blood flow velocity reached a maximum at 4 sec after the onset of negative pressure (average 44% increase above baseline, P < 0.001). Skin blood flow and skin temperature increased during all INP sequences (P < 0.001). During constant negative pressure, average blood flow velocity, skin blood flow, and skin temperature decreased (P < 0.001). In conclusion, we observed increased foot perfusion in healthy volunteers after the application of INP on the lower limb. PMID:27630148