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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. PMID:27137714

  3. 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

  4. Safety and pharmacokinetics of dicloxacillin in healthy Chinese volunteers following single and multiple oral doses

    PubMed Central

    Wu, Guolan; Zheng, Yunliang; Zhou, Huili; Hu, Xingjiang; Liu, Jian; Zhai, You; Zhu, Meixiang; Wu, Lihua; Shentu, Jianzhong

    2015-01-01

    Background Dicloxacillin, a semisynthetic isoxazolyl penicillin antibiotic, has antimicrobial activity against a wide variety of gram-positive bacteria including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumonia, Streptococcus epidermidis, Streptococcus viridans, Streptococcus agalactiae, and Neisseria meningitidis. The objective of this study was to evaluate the safety and pharmacokinetic profile of dicloxacillin after single and multiple oral dose in healthy Chinese volunteers. Methods A single-center, open-label, randomized, two-phase study was conducted in 16 subjects. In the single-dose phase, subjects were randomly assigned to receive single doses of 0.25, 0.5, 1.0, and 2.0 g of dicloxacillin sodium capsule in a 4-way crossover design with a 5-day washout period between administrations. In the multiple-dose phase, subjects were assigned to receive 0.25 or 0.5 g every 6 hours for 3 days in a 2-way crossover design. Plasma and urine pharmacokinetic samples were assayed by a validated high-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were calculated and analyzed statistically. Safety assessments were conducted throughout the study. Results Following a single oral dose of 0.25–2.0 g dicloxacillin sodium, the maximum plasma drug concentration (Cmax) and the corresponding values for the area under the concentration– time curve from 0 to 10 hours (AUC0–10 h) increased in a dose-proportional manner. The mean elimination half-life (t1/2) was in the range of 1.38–1.71 hours. Dicloxacillin was excreted in its unchanged form via the kidney, with no tendency of accumulation, and varied from 38.65% to 50.10%. No appreciable accumulation of drug occurred with multiple oral doses of dicloxacillin. No serious adverse events were reported. Adverse events were generally mild. Conclusion Dicloxacillin was safe and well tolerated in the volunteers and displayed linear increases in the Cmax and AUC0–10

  5. Safety, Tolerability, and Pharmacokinetics of Intravenous Nemonoxacin in Healthy Chinese Volunteers

    PubMed Central

    Cao, Guo-ying; Zhang, Ying-yuan; Guo, Bei-ning; Yu, Ji-cheng; Wu, Xiao-jie; Chen, Yuan-cheng; Wu, Ju-Fang; Shi, Yao-guo

    2014-01-01

    Nemonoxacin (TG-873870) is a novel nonfluorinated quinolone with potent broad-spectrum activity against Gram-positive, Gram-negative, and atypical pathogens, including vancomycin-nonsusceptible methicillin-resistant Staphylococcus aureus (MRSA), quinolone-resistant MRSA, quinolone-resistant Streptococcus pneumoniae, penicillin-resistant S. pneumoniae, and erythromycin-resistant S. pneumoniae. This first-in-human study was aimed at assessing the safety, tolerability, and pharmacokinetic properties of intravenous nemonoxacin in healthy Chinese volunteers. The study comprised a randomized, double-blind, placebo-controlled, dose escalating safety and tolerability study in 92 subjects and a randomized, single-dose, open-label, 3-period Latin-square crossover pharmacokinetic study in 12 subjects. The study revealed that nemonoxacin infusion was well tolerated up to the maximum dose of 1,250 mg, and the acceptable infusion rates ranged from 0.42 to 5.56 mg/min. Drug-related adverse events (AEs) were mild, transient, and confined to local irritation at the injection site. The pharmacokinetic study revealed that after the administration of 250, 500, and 750 mg of intravenous nemonoxacin, the maximum plasma drug concentration (Cmax) values were 4.826 μg/ml, 7.152 μg/ml, and 11.029 μg/ml, respectively. The corresponding values for the area under the concentration-time curve from 0 to 72 hours (AUC0–72 h) were 17.05 μg · h/ml, 39.30 μg · h/ml, and 61.98 μg · h/ml. The mean elimination half-life (t1/2) was 11 h, and the mean cumulative drug excretion rate within 72 h ranged from 64.93% to 77.17%. Volunteers treated with 250 to 750 mg nemonoxacin exhibited a linear dose-response relationship between the AUC0–72 h and AUC0–∞. These findings provide further support for the safety, tolerability, and pharmacokinetic properties of intravenous nemonoxacin. (This study has been registered at ClinicalTrials.gov under registration no. NCT01944774.) PMID:25092690

  6. Pharmacokinetics and Pharmacodynamics of Multiple-Dose Intravenous Nemonoxacin in Healthy Chinese Volunteers

    PubMed Central

    Wu, Xiao-jie; Guo, Bei-ning; Zhang, Ying-yuan; Yu, Ji-cheng; Cao, Guo-ying; Chen, Yuan-cheng; Zhu, De-mei; Ye, Xin-yu; Wu, Ju-fang; Shi, Yao-guo; Chang, Li-wen; Chang, Yu-ting; Tsai, Cheng-yuan

    2014-01-01

    This study evaluated the safety and pharmacokinetic/pharmacodynamic profiles of nemonoxacin in healthy Chinese volunteers following multiple-dose intravenous infusion once daily for 10 consecutive days. The study was composed of two stages. In the open-label stage, 500 mg or 750 mg of nemonoxacin (n = 12 each) was administered at an infusion rate of 5.56 mg/min. In the second stage, with a randomized double-blind placebo-controlled design, 500, 650, or 750 mg of nemonoxacin (n = 16 in each cohort; 12 subjects received the drug and the other 4 subjects received the placebo) was given at an infusion rate of 4.17 mg/min. The results showed that, in the first stage, the maximal nemonoxacin concentrations (mean ± SD) at steady state (Cmax_ss) were 9.60 ± 1.84 and 11.04 ± 2.18 μg/ml in the 500-mg and 750-mg cohorts, respectively; the areas under the concentration-time curve at steady state (AUC0–24_ss) were 44.03 ± 8.62 and 65.82 ± 10.78 μg · h/ml in the 500-mg and 750-mg cohorts, respectively. In the second stage, the nemonoxacin Cmax_ss values were 7.13 ± 1.47, 8.17 ± 1.76, and 9.96 ± 2.23 μg/ml in the 500-mg, 650-mg, and 750-mg cohorts, respectively; the AUC0–24_ss values were 40.46 ± 9.52, 54.17 ± 12.10, and 71.34 ± 17.79 μg · h/ml in the 500-mg, 650-mg, and 750-mg cohorts, respectively. No accumulation was found after the 10-day infusion with any regimen. The drug was well tolerated. A Monte Carlo simulation indicated that the cumulative fraction of response of any dosing regimen was nearly 100% against Streptococcus pneumoniae. The probability of target attainment of nemonoxacin therapy was >98% when the MIC of nemonoxacin against S. pneumoniae was ≤1 mg/liter. It is suggested that all of the studied intravenous nemonoxacin dosing regimens should have favorable clinical and microbiological efficacies in future clinical studies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01944774.) PMID:25534726

  7. 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

  8. 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

  9. Population pharmacokinetics of zonisamide after oral administration in healthy Chinese volunteers.

    PubMed

    Qiu, Xuewen; Dai, Qing; Sun, Fengjun; Liu, Yao; Yang, Bo; Xiang, Rongfeng; Yu, Mingjie; Xiong, Lirong; Bi, Shanshan; Lu, Wei; Chen, Yongchuan; Xia, Peiyuan

    2016-05-01

    To develop a population-based pharmacokinetic model for the oral antiepileptic drug zonisamide using a cohort of healthy (nonepileptic) subjects and evaluate the effect of individual factors on the pharmacokinetics of zonisamide. 30 young adults (21-39 years) in good health were randomly assigned to 3 equal groups (1:1 sex ratio) for single-dose administration of zonisamide at 200 mg, 300 mg, or 400 mg. An additional 9 subjects (22-24 years) were administered once daily zonisamide at 300 mg for 14 days, and comprised the multiple dosing group. Venous blood samples were collected for analysis prior to (baseline, 0 hours) and after (1-300 hours) drug administration, providing 607 total samples used to build the pharmacokinetic model. The population pharmacokinetic analysis was performed by ICON's nonlinear mixed-effect modeling (NONMEM) software. Validation of the final model was carried out by nonparametric bootstrapping and visual predictive check. The zonisamide pharmacokinetics was best described by a two-compartment model with first-order elimination. In the final model, the estimated value of clearance (CL) was 23.25 L/h, the volume of distribution of the central compartment (Vc) was 34.50 L, the intercompartmental clearance (Q) was 20.22 L/h, and the Ka was 0.026 h(-1). The peripheral volume of distribution (Vp) was 1,429 L for single dose and 1,003 L for multiple doses. Body weight was the significant covariate affecting CL, Vc, Vp, and Q. Otherwise, female subjects had a lower Q than male subjects. The pharmacokinetics of zonisamide after oral administration could be described using a linear first-order elimination two-compartment model, which may provide a reference for clinical use of zonisamide in Chinese adults. PMID:27007995

  10. Comparative fasting bioavailability and pharmacokinetic properties of 2 formulations of glucosamine hydrochloride in healthy Chinese adult male volunteers.

    PubMed

    Wu, H; Liu, M; Wang, S; Zhao, H; Yao, W; Feng, W; Yan, M; Tang, Y; Wei, M

    2012-08-01

    Glucosamine (CAS 66-84-2) hydrochloride is an amino monosaccharide indicated for the treatment of arthrosis, especially osteoarthritis of the knee joint. This study was conducted to assess and compare the pharmacokinetic (PK) properties, bioavailability of a newly developed dispersible tablet formulation (test) of glucosamine hydrochloride with those of an established branded capsule formulation (reference) in healthy Chinese adult male volunteers.This single-dose, randomized, open-label, 2-period crossover study was conducted in 18 healthy Chinese adult male volunteers under fasting condition. Plasma samples were collected at pre-specified times over a 12-h period following administration in each period and analyzed the plasma glucosamine concentrations by Liquid Chromatography coupled with Tandem Mass Spectrometry (LC/MS/MS) method. The mean (SD) PK parameters of Cmax, Tmax, AUC0-12, and AUC0-∞ after administration of the test and reference formulations were, respectively, as follows: Cmax, 907.01 (444.22) vs. 944.40 (429.89) ng/mL, Tmax, 3.03 (0.95) vs. 3.30 (0.99) hours, AUC0-12, 2891.41 (1352.30) vs. 2889.69 (925.48) ng/mL/h, and AUC0-∞, 3029.90 (1321.36) vs. 3091.87 (870.36) ng/mL/h. The mean (SD) t1/2 was 1.10 (0.52) hours for the test formulation and 1.50 (1.17) hours for the reference formulation. On ANOVA, neither period nor sequence effects were observed for any PK properties. The relative bioavailability of the test formulation was 98.3% assessed by AUC0-12. The 90% CIs of glucosamine for the log-transformed ratios of Cmax, AUC0-12, and AUC0-∞ were 78.4-113.9%, 80.8-108.5% and 80.8-105.8%, respectively, meeting the predetermined criteria for bioequivalence of SFDA. PMID:22791244

  11. 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

  12. 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

  13. The Lipid-lowering Effects of R-bambuterol in Healthy Chinese Volunteers: A Randomized Phase I Clinical Study

    PubMed Central

    Ye, Yanrui; Xu, Hang; Quan, Lei; Zhu, Long; Zeng, Jing; Zhou, Ting; Zou, ChengJuan; Cheng, Qing; Bu, Shujie; Tan, Wen

    2015-01-01

    Background Existing treatments are inadequate for patients at high risk of coronary heart disease caused by elevated levels of plasma low-density lipoprotein cholesterol (LDL-C). Bambuterol is a prodrug of β2-agonist commonly used for the treatment of asthma and chronic obstructive pulmonary disease (COPD) with the advantage of once daily dosing and favorable side effect profile. The potential lipid-lowering effects of bambuterol were unclear, possibly due to the racemic bambuterol (rac-bambuterol) that was used in previous studies. Methods The lipid-lowering effects of R-bambuterol were examined in a randomized phase I trial in 48 healthy Chinese volunteers aged 18–45 years. Participants were randomly assigned to five groups to receive a single dose (2.5 mg, 5 mg or 10 mg) or multiple doses (5 mg) of oral medications of R-bambuterol, or a single dose of rac-bambuterol (10 mg). Plasma lipid levels were measured at baseline, time to peak concentration (Tmax) and 24 h after the treatment. Findings Administration of a single-dose of R-bambuterol resulted in dose-dependent reductions in the levels of plasma LDL-C, high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1) at Tmax. Levels of LDL-C exhibited the most reductions, which were statistically significant in all three single-dose R-bambuterol groups (all P values < 0.05). R-bambuterol was more potent in LDL-C lowering compared to rac-bambuterol at Tmax (P = 0.08). At 24 h after dosing, the significant lipid lowering effects of R-bambuterol sustained for LDL-C (P = 0.01), ApoB (P = 0.001) and ApoA1 (P = 0.03), but not for HDL-C. The ratio of ApoA1/ApoB was marginally increased (P = 0.06). In the multiple-dose group, LDL-C levels again were significantly reduced (all P values < 0.05), whereas the ratios of ApoA1/ApoB were marginally increased. Interpretation R-bambuterol can lower the plasma levels of LDL-C, and marginally

  14. Pharmacokinetic Study of a Diclofenac Sodium Capsule Filled with Enteric-coated Pellets in Healthy Chinese Volunteers by Liquid Chromatography-electrospray Ionization-tandem Mass Spectrometry.

    PubMed

    Ma, J-Y; Liu, M; Yang, M; Zhao, H; Tong, Y; Zhang, Y; Deng, M; Liu, H

    2016-05-01

    The pharmacokinetic study of a diclofenac sodium capsule filled with enteric-coated pellets (abbreviated as CAPSULE) in healthy Chinese subjects was evaluated using liquid chromatography-electrospray ionization-tandem mass spectrometry with simple sample preparation. In a cross-over study, 12 healthy male volunteers were given 50 mg CAPSULE and diclofenac sodium enteric-coated tablet (abbreviated as TABLET, used as a control dosage form) at fasting. The Cmax, AUC0-t, and Tmax of CAPSULE were 1.01±0.52 μg/mL, 1.54±0.18 μg·h/mL, and 1.50±1.31 h, respectively. When compared with TABLET, the pharmacokinetic study showed that although this CAPSULE exhibited similar AUC (only 10% lower), it presented lower maximum plasma concentration, faster absorption and shorter time to reach maximum concentration. When compared with the previous study in Germany, obvious variations on Tmax were found in Chinese subjects taking CAPSULE, but not TABLET. The results indicated that individual difference should be paid attention when prescribing CAPSULE to Chinese patients. PMID:26418414

  15. Pharmacokinetics and tolerability of multiple-dose rosuvastatin: An open-label, randomized-sequence, three-way crossover trial in healthy Chinese volunteers

    PubMed Central

    Zhang, Ruoqi; Li, Yunxia; Jiang, Xuehua; Wang, Ling

    2009-01-01

    Background: Rosuvastatin has been reported to be beneficial in the treatment of dyslipidemia. The Cmax and AUC0−t of rosuvastatin were reported to be ~2 to 4 times higher in Chinese subjects compared with white subjects after administration of a single 1-mg/kg dose. Objectives: The aims of this study were to assess the pharmacokinetics and tolerability of multiple doses of rosuvastatin in healthy Chinese volunteers. Methods: This open-label, randomized-sequence, 3-way crossover trial consisted of three 7-day treatment periods and two 10-day washout periods. Healthy volunteers were randomly allocated to 1 of 3 daily treatment regimens: rosuvastatin 5, 10, or 20 mg. To assess the pharmacokinetics and tolerability of rosuvastatin, blood samples were drawn before dosing (hour 0) on days 5, 6, and 7 and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 15, 24, 36, 48, 72, and 96 hours after the final dose was administered on day 7. A validated HPLC-MS/MS method was used to determine rosuvastatin levels. A 2-compartment pharmacokinetic model was fitted to the plasma concentration-time profiles obtained for each volunteer. Adverse events (AEs) were monitored throughout the study via subject interview, vital signs, and blood sampling. Serious AEs were those requiring hospitalization, treatment discontinuation, or resulting in death. Results: Twelve healthy Chinese volunteers (6 men: mean [SD] age, 21.8 [1.7] years; weight, 62.3 [5.8] kg; height, 174.3 [7.2] cm; 6 women: age, 20.8 [1.2] years; weight, 53.2 [4.7] kg; height, 161.3 [4.3] cm) participated in and completed the trial. The mean (SD) steady-state Cmax was significantly greater after ro-suvastatin administration in the 20-mg group compared with the 5-mg group (37.69 [29.83] vs 6.17 [6.03] ng/mL; P = 0.04). The t1/2 was significantly greater in the 20-mg group (15.51 [6.43] hours) compared with the 5-mg group (5.65 [5.08] hours; P = 0.001) and the 10-mg group (8.58 [5.17] hours; P = 0.002). The mean AUC0−t was significantly

  16. Pharmacokinetics of betamethasone and betamethasone 17-monopropionate in Chinese healthy volunteers after intramuscular injection of betamethasone phosphate/betamethasone dipropionate.

    PubMed

    He, Chunhui; Fan, Hongwei; Tan, Jie; Zou, Jianjun; Zhu, Yubing; Yang, Kun; Hu, Qin

    2011-01-01

    The aim of this study was to evaluate the pharmacokinetic profiles of betamethasone (BOH, CAS 378-44-9) and betamethasone 17-monopropionate (B17P), the active metabolites of betamethasone phosphate (BSP) and betamethasone dipropionate (BDP), respectively, after administration of betamethasone i.m. (BSP 2 mg and BDP 5 mg). After ten healthy volunteers had received a single-dose intramuscular adminitration of betamethasone i.m., blood samples were collected pre-dose and for 336 h postdose. The plasma levels of B17P and BOH were measured by liquid chromatography-tandem mass spectrometry (LC-MS/ MS). When compared to BOH, B17P exhibited a longer time to maximum concentration (15.0 +/- 9.0 h vs. 2.8 +/- 1.7 h), a lower Cmax (0.6 +/- 0.2 ng/mL vs. 14.5 +/- 3.7 ng/mL), and a much longer half-life (80.8 +/- 22.7 h vs. 9.6 +/- 3.6 h). Betamethasone i.m. produced rapid onset and sustained action through an initial rapid-increased plasma concentration of BOH and a sustained plasma concentration of B17P, respectively. PMID:21899210

  17. 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

  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. PMID:26519688

  20. Cryptosporidium meleagridis: Infectivity in Healthy Adult Volunteers

    PubMed Central

    Chappell, Cynthia L.; Okhuysen, Pablo C.; Langer-Curry, Rebecca C.; Akiyoshi, Donna E.; Widmer, Giovanni; Tzipori, Saul

    2011-01-01

    Most Cryptosporidium infections in humans are caused by C. parvum or C. hominis. However, genotyping techniques have identified infections caused by unusual Cryptosporidium species. Cryptosporidium meleagridis has been identified in ≤ 1% of persons with diarrhea, although prevalence is higher in developing nations. We examined the infectivity of C. meleagridis in healthy adults. Five volunteers were challenged with 105 C. meleagridis oocysts and monitored six weeks for fecal oocysts and clinical manifestations. Four volunteers had diarrhea; three had detectable fecal oocysts; and one infected volunteer remained asymptomatic. Fecal DNA from two volunteers was amplified by using a polymerase chain reaction specific for the Cryptosporidium small subunit ribosomal RNA gene. Nucleotide sequence of these amplicons was diagnostic for C. meleagridis. All infections were self-limited; oocysts were cleared within ≤ 12 days of challenge. These studies establish that healthy adults can be infected and become ill from ingestion of C. meleagridis oocysts. PMID:21813841

  1. Desipramine pharmacokinetics in Chinese and Caucasian volunteers.

    PubMed Central

    Rudorfer, M V; Lane, E A; Chang, W H; Zhang, M D; Potter, W Z

    1984-01-01

    In order to better define the role of pharmacokinetic variation in reported cross-ethnic differences in dosing patterns of some psychoactive drugs, single dose kinetics of the tricyclic antidepressant desipramine (DMI) were studied in 14 Chinese and 16 Caucasian healthy volunteers. DMI and 2-OH-DMI concentrations were assayed with h.p.l.c. in serial plasma and 24 h urine samples over 5 days following an oral 100 mg dose of DMI. Mean total clearance of DMI ( CLDMI ) from plasma was significantly (P less than 0.05) higher in the Caucasians (123 +/- 57 l/h) than in the Chinese (73.5 +/- 38.8 l/h). There was no significant difference in the apparent clearance of DMI by hydroxylation, fraction of dose metabolized to the hydroxy metabolite, DMI t1/2 or plasma protein binding between the two groups. Trimodal distribution of CLDMI was found, with 4/14 (29%) Chinese demonstrating slow CL (less than 33 l/h) and 4/16 (25%) Caucasians rapid CL (greater than 195 l/h). Correcting CL values for the greater mean weight of the Caucasians did not alter the pattern of distribution. CLDMI did not correlate with body weight. Although environmental factors cannot be ruled out, these results are consistent with genetically based differences in hepatic metabolism, probably affecting pathways in addition to hydroxylation, and suggest that 30% of Orientals would be at risk for toxicity from routine doses of tricyclics or similarly metabolized drugs. PMID:6721989

  2. Simultaneous determination of rupatadine and its metabolite desloratadine in human plasma by a sensitive LC-MS/MS method: application to the pharmacokinetic study in healthy Chinese volunteers.

    PubMed

    Wen, Jun; Hong, Zhanying; Wu, Yiwen; Wei, Hua; Fan, Guorong; Wu, Yutian

    2009-02-20

    A sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed for simultaneous determination of rupatadine and its metabolite desloratadine in human plasma. After the addition of diphenhydramine, the internal standard (IS), plasma samples were extracted with a mixture of methyl tert-butyl ether and n-hexane (1:1, v/v). The analysis was performed on a Ultimate AQ-C18 (4.6mm x 100mm, 5microm) column using a mobile phase consisting of a 80/20 mixture of methanol/water containing 0.0005% formic acid pumped at 0.3mlmin(-1). The analytes and the IS were detected in positive ionization mode and monitoring their precursor-->product ion combinations of m/z 416-->309, 311-->259, and 256-->167, respectively, in multiple reaction monitoring mode. The linear ranges of the assay were 0.1-50 and 0.1-20ngml(-1) for rupatadine and desloratadine, respectively. The lower limits of reliable quantification for both rupatadine and desloratadine were 0.1ngml(-1), which offered high sensitivity and selectivity. The within- and between-run precision was less than 7.2%. The accuracy ranged from -9.2% to +6.4% and -7.2% to +7.2% for rupatadine and desloratadine in quality control samples at three levels, respectively. The method has been successfully applied to a pharmacokinetic study of rupatadine and its major metabolite after oral administration of 10, 20 and 40mg rupatadine tablets to healthy Chinese volunteers. PMID:19059745

  3. 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. PMID:25070094

  4. 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. PMID:27413680

  5. Effect of grapefruit juice and food on the pharmacokinetics of pirfenidone in healthy Chinese volunteers: a diet-drug interaction study.

    PubMed

    Hu, Jinqing; Shang, Dewei; Xu, Xinwen; He, Xiuling; Ni, Xiaojia; Zhang, Ming; Wang, Zhanzhang; Qiu, Chang; Deng, Shuhua; Lu, Haoyang; Zhu, Xiuqing; Huang, Wencan; Wen, Yuguan

    2016-06-01

    1. Ingestion of grapefruit juice and food could be factors affecting the pharmacokinetics of pirfenidone, a promising drug for treatment of idiopathic pulmonary fibrosis. 2. A randomized, open-label, three-period crossover study was carried out in 12 healthy Chinese male volunteers who were randomized to one of the three treatments: pirfenidone tablets (0.4 g) were orally administered to fasted or fed subjects, or with grapefruit juice. The washout period was 7 d. 3. Significantly reduced maximum plasma concentration (Cmax, 5.0 5 ± 1.39 versus 10.9 0 ± 2.94 mg·L(- 1)), modestly affected area-under-the-plasma concentration-time curve (AUC) from time zero to 12 h post dosing (AUC0-12 h, 21.8 9 ± 6.47 versus 26.1 6 ± 7.32 mg·h·L(- 1)) and delayed time to reach Cmax (Tmax) were observed in fed group compared with fasted group. Similar effects on Cmax (5.8 2 ± 1.23 versus 10.9 0 ± 2.94 mg·L(- 1)) and AUC0-12 h (modest but not statistically significant, 24.4 4 ± 7.40 versus 26.1 6 ± 7.32 mg·h·L(- 1)) were observed for grapefruit juice compared to fasted subjects. 4. Co-administration of pirfenidone with grapefruit juice resulted in modestly reduced overall oral absorption and significantly reduced peak concentrations compared to fasting, which was similar to effect of food ingestion. No adverse events were observed in the study, but relatively dramatic reduction of peak concentrations should raise concerns for clinical efficacy and safety. PMID:26407124

  6. CYP3A5*3 and MDR1 C3435T are influencing factors of inter-subject variability in rupatadine pharmacokinetics in healthy Chinese volunteers.

    PubMed

    Xiong, Yuqing; Yuan, Zhao; Yang, Jingzhi; Xia, Chunhua; Li, Xinhua; Huang, Shibo; Zhang, Hong; Liu, Mingyi

    2016-04-01

    Rupatadine (RUP) is an oral antihistamine and platelet-activating factor antagonist and is shown as the substrate of CYP3A5 and P-gp. The significant interindividual differences of CYP3A5 and P-gp often cause bioavailability differences of some clinical drugs. The present study is aimed to evaluate the effect of genetic polymorphisms of CYP3A5 and MDR1 on RUP pharmacokinetics in healthy male Chinese volunteer subjects. Blood samples were collected from 36 subjects before and after a single, oral RUP 10 mg dose. A PCR-RFLP assay was used to genotype CYP3A5*3 and assess MDR1 C3435T variation. A validated LC-MS/MS method quantified plasma RUP concentration. The relationship between RUP plasma concentration, pharmacokinetic parameters, and polymorphic alleles (CYP3A5 and MDR1) were assessed. Plasma RUP concentrations were lower for CYP3A5*1/*1 carriers than for CYP3A5*3/*3 and CYP3A5*1/*3 carriers. Mean C(max), AUC(0-t) and AUC(0-∞) were significantly lower, and the CLz and Vd were significantly higher in the CYP3A5 wild-type group, than in the CYP3A5 mutated group. MDR1 CT and MDR1 TT carriers had lower plasma RUP concentrations than MDR1 CC carriers. The mean C(max), AUC(0-t), AUC(0-∞) and T max were significantly lower in the TT group than in the CC and CT groups. The mean CLz was higher in the TT group than in the CC and CT groups, but not significantly. These results suggest that CYP3A5 and MDR1 may play a key role in the variability of RUP metabolism and transport, respectively. CYP3A5 and MDR1 polymorphisms may be the main explanation for the differences observed in RUP pharmacokinetics, and therefore may provide a rationale for safe and effective clinical use of RUP. Our research lays down a solid theory foundation to guide the safe and effective clinical use of RUP and a route to achieve individualized therapy. PMID:25427746

  7. 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

  8. 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

  9. 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

  10. Relative bioequivalence evaluation of two oral atomoxetine hydrochloride capsules: a single dose, randomized, open-label, 2-period crossover study in healthy Chinese volunteers under fasting conditions.

    PubMed

    Shang, D-W; Guo, W; Zhou, F-C; Wang, X-P; Li, A-N; Zhang, L; Li, W-B; Lu, W; Wang, C-Y

    2013-11-01

    To evaluate the bioequivalence of a new formulation of atomoxetine hydrochloride (CAS 82248-59-7) capsules (test) and an available branded capsules (reference) after administration of a single 40 mg dose, randomized, open-label, 2-period crossover study was conducted in 22 healthy male Chinese subjects with a 1-week wash-out period. This study was designed for/the Honglin Pharmaceutical Co. Ltd and contracted to be done by the Beijing Anding Hospital in order to satisfy Chinese regulatory requirements to allow marketing of this generic product and performed according to the criteria of SFDA. Blood samples were collected before and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16 and 24 h after drug administration. Plasma concentrations were determined by high-performance liquid chromatography (HPLC) with UV detection. A non-compartmental method was used to calculate the pharmacokinetic parameters and evaluate bioequivalence of the 2 formulations. The 90% confidence interval (CI) of the ratios (test/reference) of atomoxetine for AUC0-24, AUC0-∞ and Cmax were 100.9% (93.6-108.8%), 103.1% (95.1-111.7%) and 105.2% (92.8-119.4%), respectively, which fell within the interval of 80-125% and 75-133%. No clinically significant changes or abnormalities were noted in laboratory data and vital signs. From these results it can be concluded that the test formulation of atomoxetine capsules met the regulatory criterion for bioequivalence to the reference formulation. PMID:23812961

  11. 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

  12. 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

  13. Pharmacokinetics of cefoperazone in healthy volunteers.

    PubMed

    Saudek, F; Morávek, J; Modr, Z

    1986-01-01

    Pharmacokinetics of cefoperazone was studied in 10 healthy volunteers following 15 min intravenous infusion of 2 g. Cefoperazone levels in the blood serum and in the urine were determined microbiologically. At the end of the infusion, mean serum concentrations of the antibiotic were 340.4 (+/- 81.5) mg/l, at the 4th hour after the infusion 38.4 (+/- 10.3) mg/l, and 12 hours after the infusion all subjects had detectable concentrations with the mean value 2.2 (+/- 0.7) mg/l. Within 12 hours, 33.3 (+/- 6.1) % of the total dose of cefoperazone had been eliminated in the urine. The fitting of the individual serum concentration curves and the determination of pharmacokinetic constants were done according to a two-compartment model with the aid of nonlinear least-squares regression analysis on a programmable calculator TI 59. The mean value of the biological half-life (beta phase) of cefoperazone was 1.77 (+/- 0.25) h, mean serum clearance was 61.7 (+/- 12.1) ml/min and the mean distribution volume (Vd area) was 9.44 (+/- 2.2) 1. Our data are in agreement with those previously reported in the literature. The only exception is the distribution volume, which we found to be smaller. PMID:3095076

  14. 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

  15. [Drug evaluation in healthy volunteers. Legislative and ethical aspects].

    PubMed

    Warot, D

    1991-01-01

    Studies in healthy volunteers have been legalized since December 20th 1988 in France. The healthy volunteer is employed for a variety of studies in phases I and IV of drug development. This type of research can equally be called nontherapeutic in nature. Every experiment involving healthy volunteers should be approved by the Ethics Committee. Using volunteers within the department, company or other organisation, while offering advantages for the investigator should be prohibited as freedom of concept might not be safeguarded. As well, financial incentives may over-persuade individuals, including students, who have low incomes and promote the "professional volunteer". To avoid this problem, French law planned a national register. The potential benefits of such a disposition are still unknown. Having been given appropriate information concerning the drug trial, his obligations and rights, the healthy volunteer gives his written consent. Specific recommendations for nontherapeutic assessments of drug effects are given concerning prisoners, the mentally handicapped, women with a risk of frequency, children. Ethical considerations concerning research on a healthy population must go beyond the law recently promulgated in France. PMID:2050001

  16. Reactivity of allergy skin test in healthy volunteers

    PubMed Central

    Supakthanasiri, Phisit; Klaewsongkram, Jettanong; Chantaphakul, Hiroshi

    2014-01-01

    INTRODUCTION Healthy individuals may be exposed and sensitised to allergens, and have a positive response to a skin prick test despite being asymptomatic. The objectives of this study were to evaluate the prevalence of atopic sensitisation and identify the reactivity of healthy volunteers to common aeroallergens. METHODS Healthy volunteers with no known allergic symptoms were recruited in this study. All volunteers were scheduled to undergo a skin prick test with 16 common aeroallergens that were previously identified among atopic patients. RESULTS A total of 100 volunteers (mean age 28 years) were enrolled in this study. 42 volunteers had positive skin prick tests for at least one allergen. The median number of sensitised allergen was 2 (range 1–7). Volunteers with positive skin tests (n = 42) were younger than those with negative skin tests (n = 58) (mean age 25.5 vs. 29.2 years; p < 0.05). The group with positive skin tests also had a higher proportion of males (57.1% vs. 31.0%; p < 0.01) and first-degree relatives with a history of atopic diseases (31.0% vs. 10.3%; p < 0.05). The most common sensitised allergens in these healthy asymptomatic volunteers were mite (n = 33), house dust (n = 23) and American cockroach (n = 20). CONCLUSION In this study, up to 42% of healthy volunteers, particularly those with a family history of atopy, were sensitised to allergens. Reactivity of the skin test without allergic symptoms, however, does not indicate allergic disease. Therefore, the skin test should only be indicated in atopic symptomatic individuals. PMID:24452975

  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. 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

  20. Self-selection for personality variables among healthy volunteers.

    PubMed

    Pieters, M S; Jennekens-Schinkel, A; Schoemaker, H C; Cohen, A F

    1992-01-01

    1. Healthy student volunteers (n = 103) participating in ongoing clinical pharmacological research completed the Dutch Personality Inventory (DPI), the Dutch version of the Spielberger State-Trait Anxiety Inventory (STAI-DY) and the Dutch version of the Sensation Seeking Scale (SSS). 2. The volunteers were more extrovert (P less than 0.001), more flexible (P less than 0.001), more tolerant or less impulsive (P less than 0.001), had more self-confidence and initiative (P less than 0.001), and were more satisfied and optimistic (P less than 0.01) when compared with the general norm. When compared with a student norm, volunteers had lower levels of state (P less than 0.001) and trait (P less than 0.05) anxiety. The general sensation seeking tendency of volunteers was higher than in the student norm group (P less than 0.001). The volunteers had a greater tendency to thrill-and-adventure-seeking (P less than 0.001) and to disinhibition (P less than 0.01). 3. Hence, volunteers were a selected sample of the total population of students. This may influence the interpretation of pharmacokinetic and pharmacodynamic parameters. 4. Personality screening should be added to the screening procedures for volunteers. PMID:1540478

  1. Cryptosporidium muris: Infectivity and Illness in Healthy Adult Volunteers

    PubMed Central

    Chappell, Cynthia L.; Okhuysen, Pablo C.; Langer-Curry, Rebecca C.; Lupo, Philip J.; Widmer, Giovanni; Tzipori, Saul

    2015-01-01

    Although Cryptosporidium parvum and C. hominis cause the majority of human cryptosporidiosis cases, other Cryptosporidium species are also capable of infecting humans, particularly when individuals are immunocompromised. Ten C. muris cases have been reported, primarily in human immunodeficiency virus (HIV) -positive patients with diarrhea. However, asymptomatic cases were reported in two HIV-negative children, and in another case, age and immune status were not described. This study examines the infectivity of C. muris in six healthy adults. Volunteers were challenged with 105 C. muris oocysts and monitored for 6 weeks for infection and/or illness. All six patients became infected. Two patients experienced a self-limited diarrheal illness. Total oocysts shed during the study ranged from 6.7 × 106 to 4.1 × 108, and the number was slightly higher in volunteers with diarrhea (2.8 × 108) than asymptomatic shedders (4.4 × 107). C. muris-infected subjects shed oocysts longer than occurred with other species studied in healthy volunteers. Three volunteers shed oocysts for 7 months. Physical examinations were normal, with no reported recurrence of diarrhea or other gastrointestinal complaints. Two persistent shedders were treated with nitazoxanide, and the infection was resolved. Thus, healthy adults are susceptible to C. muris, which can cause mild diarrhea and result in persistent, asymptomatic infection. PMID:25311695

  2. Repeat participation among normal healthy research volunteers: professional guinea pigs in clinical trials?

    PubMed

    Tishler, Carl L; Bartholomae, Suzanne

    2003-01-01

    The recent death of a normal healthy volunteer, as well as the increased use of normal volunteers as research subjects, has heightened the attention given to the participation of normal volunteers in clinical research. An overlooked sub-population of normal healthy volunteers are repeat, veteran volunteers. This essay discusses ethical and methodological issues associated with the use of repeat volunteers in research, along with existing guidelines regarding the use of repeat healthy volunteers, and concludes with recommendations for safeguarding repeat volunteers and ideas supporting centralized recruiting. PMID:14593220

  3. Nebivolol decreases systemic oxidative stress in healthy volunteers

    PubMed Central

    Troost, R; Schwedhelm, E; Rojczyk, S; Tsikas, D; Frölich, J C

    2000-01-01

    Aims Nebivolol is a selective, vasodilatory β1-adrenergic receptor antagonist which has been suggested to possess additional antioxidative properties. The aim of the present study was to assess the actions of nebivolol in antihypertensive doses on systemic oxidative stress in healthy volunteers, reflected by 24h urinary excretion of 8-iso-PGF2α. Methods In a double-blind, cross-over study, 12 healthy volunteers received 5 mg nebivolol once daily or placebo for a total of 7 days, separated by a wash out period of 2 weeks. After each treatment period 24h urinary excretion of 8-iso-PGF2α was determined by gas chromatography-tandem mass spectrometry. Results After the 7 day treatment period nebivolol decreased significantly urinary excretion of 8-iso-PGF2α by 24% from 55.3 ± 5.1 pmol mmol−1 creatinine during the placebo period to 42.3 ± 4.7 pmol mmol−1 creatinine (mean ± s.e. mean, P = 0.01), a mean decrease of 13 pmol mmol−1 creatinine (95% CI: −22.8; −3.1). Conclusions Our data show for the first time that nebivolol decreases systemic oxidative stress in young healthy volunteers. PMID:11012562

  4. Safety assessment of inhaled xylitol in mice and healthy volunteers

    PubMed Central

    Durairaj, Lakshmi; Launspach, Janice; Watt, Janet L; Businga, Thomas R; Kline, Joel N; Thorne, Peter S; Zabner, Joseph

    2004-01-01

    Background Xylitol is a 5-carbon sugar that can lower the airway surface salt concentration, thus enhancing innate immunity. We tested the safety and tolerability of aerosolized iso-osmotic xylitol in mice and human volunteers. Methods This was a prospective cohort study of C57Bl/6 mice in an animal laboratory and healthy human volunteers at the clinical research center of a university hospital. Mice underwent a baseline methacholine challenge, exposure to either aerosolized saline or xylitol (5% solution) for 150 minutes and then a follow-up methacholine challenge. The saline and xylitol exposures were repeated after eosinophilic airway inflammation was induced by sensitization and inhalational challenge to ovalbumin. Normal human volunteers underwent exposures to aerosolized saline (10 ml) and xylitol, with spirometry performed at baseline and after inhalation of 1, 5, and 10 ml. Serum osmolarity and electrolytes were measured at baseline and after the last exposure. A respiratory symptom questionnaire was administered at baseline, after the last exposure, and five days after exposure. In another group of normal volunteers, bronchoalveolar lavage (BAL) was done 20 minutes and 3 hours after aerosolized xylitol exposure for levels of inflammatory markers. Results In naïve mice, methacholine responsiveness was unchanged after exposures to xylitol compared to inhaled saline (p = 0.49). There was no significant increase in Penh in antigen-challenged mice after xylitol exposure (p = 0.38). There was no change in airway cellular response after xylitol exposure in naïve and antigen-challenged mice. In normal volunteers, there was no change in FEV1 after xylitol exposures compared with baseline as well as normal saline exposure (p = 0.19). Safety laboratory values were also unchanged. The only adverse effect reported was stuffy nose by half of the subjects during the 10 ml xylitol exposure, which promptly resolved after exposure completion. BAL cytokine levels were

  5. 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

  6. 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

  7. Immediate effects of two relaxation techniques on healthy volunteers.

    PubMed

    Khemka, Sushilkumar S; Rao, Nagendra H Rama; Nagarathna, Raghuram

    2009-01-01

    This controlled study compared immediate effects of two relaxation techniques on state anxiety and sustained attention in healthy subjects. 86 volunteers (56 men and 30 women) were divided into two groups: the first 43 volunteers (age range 18 to 64) practiced 20 minutes of yoga-based Deep Relaxation Technique (DRT), while the second group of 43 volunteers (same age range), practiced 20 minutes Supine Rest (SR). State anxiety was assessed using the State Trait Anxiety Inventory (STAI A-State), and sustained attention was assessed using the Six Letter Cancellation (SLC) and Digit Letter Substitution (DLS) tests. All tests were administered immediately before, and immediately after, practice. A significant reduction in State Anxiety score (P < 0.001) was observed for the group practicing DRT, but not for the group practicing SR. For the sustained attention tests, however, there were significant increases in scores by both DRT and SR groups (P < 0.001). The results suggest that both interventions improve attention, but that only DRT reduces State Anxiety. PMID:19810579

  8. 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

  9. 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

  10. 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

  11. 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

  12. Apomorphine-induced blinking and yawning in healthy volunteers.

    PubMed Central

    Blin, O; Masson, G; Azulay, J P; Fondarai, J; Serratrice, G

    1990-01-01

    Yawning and spontaneous blink rate (SBR) are two physiological reflexes which have been incompletely examined but one neurobiological step of these two behaviours seems, at least in part, dopamine-dependent. The reference dopaminergic agonist, apomorphine hydrochloride (0.5, 1, and 2 micrograms kg-1 s.c.), was compared with a placebo in a double-blind latin-square design, and was shown to induce yawning and increase SBR in a population of eight healthy volunteers. These two behavioral effects were not dose-related. The individual SBR differences were correlated with the individual number of yawns for all the four treatments at the 10-30 min interval. Thus, parallel yawning and SBR behaviour suggests a similar pharmacological mechanism. Apomorphine-induced yawning and blinking may be therefore of use in the evaluation of central dopaminergic pathways in man. PMID:2271377

  13. Memory and psychomotor effects of oxcarbazepine in healthy human volunteers.

    PubMed

    Curran, H V; Java, R

    1993-01-01

    Cognitive and psychomotor impairments can be unwanted adverse effects of antiepileptic drugs. The present double-blind, cross-over study with healthy volunteers was designed to assess the effects of two doses of oxcarbazepine (OXCZ) (150 mg b.i.d.; 300 mg b.i.d.) and a placebo, each given over a two week period. Twelve subjects completed a battery of tests before and 4 h after morning doses on days 1, 8 and 15. Results of objective tests indicated that OXCZ improved performance on a focussed attention task and increased manual writing speed. Subjective ratings showed OXCZ increased feelings of altertness, clear-headedness and quickwittedness. OXCZ had no effect on the range of long-term memory processes assessed in this study. It is concluded that at the doses employed, OXCZ has a slightly stimulant effect on some aspects of psychomotor functioning. PMID:8405007

  14. 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

  15. Comparison of aspirin and indobufen in healthy volunteers.

    PubMed

    Lee, Jong-Young; Sung, Ki-Chul; Choi, Hyo-In

    2016-01-01

    The aim of this study is to quantify the extent and recovery of platelet inhibition after administration of indobufen and aspirin in healthy volunteers. Indobufen inhibits platelet aggregation by reversibly inhibiting the platelet cyclooxygenase enzyme, thereby suppressing thromboxane synthesis. Twenty healthy volunteers completed the study and received aspirin (200 mg/day for 2 weeks) followed by a 4-week washout period and then indobufen (200 mg twice a day for 2 weeks). The percent (%) inhibition of platelet aggregation (IPA) was assessed using arachidonic acid (0.5 mg/ml) and adenosine diphosphate (5 µM) at 4, 12, 24 and 48 hours after last dose of each drug. IPA assessed using arachidonic acid as the agonist was similar at 4 hours after the last dose of indobufen (81.07 ± 9.36%) and aspirin (96.99 ± 0.29%, p = 0.10), but significantly lower at 12 hours (74.04 ± 9.55% vs. 97.94 ± 0.28%, p = 0.02), 24 hours (33.39 ± 11.13% vs. 97.48 ± 0.32%, p < 0.001) and 48 hours (14.12 ± 9.74% vs. 98.22 ± 0.31%, p < 0.001) after indobufen, compared to the relative values for aspirin. IPA assessed using adenosine diphosphate as the agonist was similar in the two groups at 4, 12 and 24 hours after the last dose, but significantly lower 48 hours after the last dose of indobufen, compared to the relative value for aspirin (1.98 ± 3.57% vs. 12.61 ± 2.71%, p = 0.002). Indobufen (200 mg twice a day) caused equivalent initial inhibition of platelet aggregation to aspirin (200 mg daily), and the anti-aggregation effect diminished faster than after aspirin. PMID:26083594

  16. 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

  17. Dose Proportionality of Fentanyl Buccal Tablet in Healthy Japanese Volunteers

    PubMed Central

    Darwish, Mona; Tempero, Kenneth; Jiang, John G; Thompson, Jeffrey; Simonson, Philip G

    2008-01-01

    Objective This study was conducted to assess the dose proportionality, safety, and tolerability of fentanyl buccal tablet (FBT) in Japanese volunteers. Methods Healthy, opioid-naive Japanese adults received single-dose FBT 100, 200, 400, and 800 µg in a randomized, open-label, crossover fashion. Naltrexone was given to minimize the opioid effects of fentanyl. Peak serum fentanyl concentration (Cmax), time to Cmax (tmax), area under the serum fentanyl concentration-time curve (AUC) from time 0 to infinity (AUC0–∞), and AUC from 0 to the last quantifiable concentration (AUC0–last) were summarized using descriptive statistics. Dose proportionality was claimed if the ln-ln plots of Cmax, AUC0–∞, and AUC0–last vs. dose were linear and the 90% confidence intervals (CI) of the slopes were within 0.8927 and 1.1073. The safety population comprised volunteers who received ≥1 FBT. Results Twenty-five volunteers were enrolled, 23 were included in the safety population (mean age 35.3 years), and 19 completed the study. The assessment of dose proportionality did not meet the statistical criteria (slope [90% CI]: 0.9118 [0.8601, 0.9635] for Cmax, 1.0756 [1.0377, 1.1136] for AUC0–∞, and 1.0992 [1.0677, 1.1307] for AUC0–last). However, the increase in systemic exposure with dose appeared linear, and a post hoc analysis of partial AUCs from time 0 to 8, 12, 18, and 24 hours supported dose proportionality. Median tmax of 90 minutes (range 30–180 minutes) was independent of dose. Adverse events (AEs) were mild or moderate. The most frequent AEs were nausea (N = 9), dizziness (N = 8), headache (N = 6), somnolence (N = 6), dyspepsia (N = 5), and vomiting (N = 3). No application-site or serious AEs were reported. Conclusions Systemic exposure to FBT was approximately dose proportional across the range 100 µg to 800 µg in healthy Japanese adults. Adverse events were mild or moderate. PMID:19915713

  18. 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

  19. 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

  20. Tryptophan supplementation and the response to unfairness in healthy volunteers

    PubMed Central

    Cerit, Hilâl; Schuur, Rachel J.; de Bruijn, Ellen R. A.; Van der Does, Willem

    2015-01-01

    Experimental manipulation of serotonin (5-HT) availability has been shown to modulate social behavior. For instance, serotonin depletion increased the rejection rates of unfair offers in the ultimatum game (UG), whereas a single dose of the serotonin reuptake inhibitor (citalopram) decreased rejection rates. These effects were observed immediately after the manipulation. The aim of this study was to investigate the effect of prolonged tryptophan (TRP) supplementation on UG performance in healthy individuals. A randomized double-blind placebo (PLC)-controlled design was used. Healthy volunteers (N = 47) completed the UG before and after a 6-day intervention of TRP (2.8 g/day) or PLC. Impulsivity was measured with a Go-Stop task. The overall analyses showed that TRP supplementation had no significant effect on UG scores, but the direction of the effect was opposite from expectations. Because repeated performance of the UG may lead to unwanted learning effects or strategical changes, additional analyses were conducted in which participants (N = 7) who accepted all offers on the second measurement were excluded. These analyses revealed that the TRP-group rejected very unfair offers more often than the PLC group. The groups did not differ on impulsivity. Increasing serotonin through TRP supplements increased the rejection of very unfair offers. The direction of our findings is inconsistent with earlier studies that showed that increasing 5-HT availability results in less rejection of unfair offers. The current findings thus importantly suggest that effects of acute vs. prolonged enhancement of 5-HT availability may differ. Also, the outcomes show that the UG is a complex task and participants’ decisions may depend on context, e.g., prior experience with the task. PMID:26236273

  1. Salvia lavandulaefolia (Spanish sage) enhances memory in healthy young volunteers.

    PubMed

    Tildesley, N T J; Kennedy, D O; Perry, E K; Ballard, C G; Savelev, S; Wesnes, K A; Scholey, A B

    2003-06-01

    Sage (Salvia) has a longstanding reputation in British herbal encyclopaedias as an agent that enhances memory, although there is little evidence regarding the efficacy of sage from systematized trials. Based on known pharmacokinetic and binding properties, it was hypothesised that acute administration of sage would enhance memory in young adult volunteers. Two experiments utilised a placebo-controlled, double-blind, balanced, crossover methodology. In Trial 1, 20 participants received 50, 100 and 150 microl of a standardised essential oil extract of Salvia lavandulaefolia and placebo. In Trial 2, 24 participants received 25 and 50 microl of a standardised essential oil extract of S. lavandulaefolia and placebo. Doses were separated by a 7-day washout period with treatment order determined by Latin squares. Assessment was undertaken using the Cognitive Drug Research computerised test battery prior to treatment and 1, 2.5, 4 and 6 h thereafter. The primary outcome measures were immediate and delayed word recall. The 50 microl dose of Salvia essential oil significantly improved immediate word recall in both studies. These results represent the first systematic evidence that Salvia is capable of acute modulation of cognition in healthy young adults. PMID:12895685

  2. [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

  3. 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

  4. Pharmacokinetics of cefroxadine after infusion to healthy volunteers.

    PubMed

    Cadórniga, R; Molina, I T; Pastoriza, P; Negro, S; Evora, C M; Gutierrez, J A

    1990-10-01

    The pharmacokinetics of cefroxadine in healthy human volunteers was studied in plasma and urine, after an infusion administration of 1 g of this drug for 0.5 h. Blood and urine samples were microbiologically quantified by diffusion on solid gelose using Bacillus Subtilis ATCC 6633 as the test organism. Plasma and urine profiles were fitted to a reduced two-compartment model not having inactivating biotransformation as a route of elimination. The parameters of distribution for this model show a rapid disposition (t1/2 alpha = 0.28 h) and an average volume of the central compartment of 0.15 +/- 0.04 l/kg (range 0.20-0.09). The dominant terminal half-life (beta-phase) was 1.17 +/- 0.26 h (range 0.90-1.67). The total body volume 0.41 +/- 0.09 l/kg (range 0.30-0.52) indicates that there is no diffusion of the antibiotic into intracellular fluids of poorly perfused tissues due to its high elimination rate. PMID:2258253

  5. Interaction between ketoconazole and almotriptan in healthy volunteers.

    PubMed

    Fleishaker, Joseph C; Herman, Beth D; Carel, Barbara J; Azie, Nkechi E

    2003-04-01

    The interaction between almotriptan, a 5-HT1B/1D agonist, and the potent CYP3A4 inhibitor ketoconazole was examined in 16 healthy volunteers. Subjects received (A) 12.5 mg almotriptan orally on Day 2 of a 3-day regimen of 400 mg ketoconazole once daily and (B) 12.5 mg almotriptan in a crossover design. Plasma and urine concentrations of almotriptan were measured by HPLC. Treatment effects on almotriptan pharmacokinetics were assessed by analysis of variance. Ketoconazole coadministration increased mean almotriptan AUC and Cmax from 312 to 490 ng h/mL and 52.6 to 84.5 ng/mL, respectively. Mean oral clearance was decreased from 40.7 to 26.2 L/h by ketoconazole, with an accompanying increase in the fraction of almotriptan excreted unchanged in the urine (40.6% to 53.3%) and a decrease in renal clearance (16.4 to 13.8 L/h). These effects were statistically significant. The effects of ketoconazole on almotriptan clearance were consistent with inhibition of the CYP3A4-mediated metabolism and a slight effect on the active tubular secretion of almotriptan. PMID:12723463

  6. Pharmacokinetics and safety of oral almotriptan in healthy male volunteers.

    PubMed

    McEwen, J; Salva, M; Jansat, J M; Cabarrocas, X

    2004-10-01

    Almotriptan (LAS 31416) is a new, oral, specific 5-hydroxytryptamine(1B/1D) receptor agonist for the treatment of migraine. The pharmacokinetics and safety of a range of oral doses were assessed in 23 healthy male volunteers. Peak plasma concentrations were reached between 1.5 and 4 h after dosing. The maximum plasma concentration and area under the curve showed dose proportionality over the dose range 5-200 mg. The elimination half-life was constant at approximately 3 h across all dose levels. A substantial proportion of the initial dose was excreted in urine (27%-39%) during 12 h post-dose and the main excretory product was unchanged drug. Three major urinary metabolites were detected, all of which were pharmacologically inactive. The most common events following almotriptan administration were headache, tiredness and mild nausea. Nine events (18%) were classed as probably related to almotriptan and these were all at the highest dose level of 200 mg. The maximum tolerated dose of almotriptan was, therefore, determined as 150 mg. In conclusion, almotriptan is well tolerated following single, oral doses up to 150 mg and has predictable pharmacokinetics. PMID:15386481

  7. Effect of faldaprevir on raltegravir pharmacokinetics in healthy volunteers.

    PubMed

    Joseph, David; Rose, Peter; Strelkowa, Natalja; Schultz, Armin; Garcia, Jeanette; Elgadi, Mabrouk; Huang, Fenglei

    2015-04-01

    Faldaprevir is a potent hepatitis C virus (HCV) NS3/4A protease inhibitor and an inhibitor of UDP-glucuronosyltransferase-1A1 (UGT1A1), which is involved in raltegravir clearance. Raltegravir, an HIV integrase inhibitor, may be used in combination with HCV treatment in HCV/HIV co-infected patients. In this open-label, 2-period, fixed-sequence study, 24 healthy volunteers (12 males) received faldaprevir 240 mg and raltegravir 400 mg in 2 treatment schedules (A and B) separated by a washout phase of ≥7 days: (A) twice-daily raltegravir (Days 1-3), once-daily raltegravir (Day 4); (B) twice-daily raltegravir and twice-daily faldaprevir (loading dose, Day 1), twice-daily raltegravir and once-daily faldaprevir (Days 2-5), once-daily raltegravir and once-daily faldaprevir (Day 6). Pharmacokinetics and safety were assessed over 132 hours post-dosing. Compared with raltegravir alone, co-administration with faldaprevir led to 2.7-fold and 2.5-fold increases in raltegravir geometric mean AUC(τ,ss) and C(max,ss), respectively, and a similar increase in raltegravir glucuronide metabolite exposure. No serious adverse events (AEs) were reported and no subject discontinued due to AEs. Faldaprevir and raltegravir co-administration was well tolerated and resulted in a moderate increase in raltegravir exposure. PMID:25352040

  8. Pomelo enhances cyclosporine bioavailability in healthy male Thai volunteers.

    PubMed

    Anlamlert, Wirin; Sermsappasuk, Pakawadee; Yokubol, Dhirayudh; Jones, Sirada

    2015-04-01

    The aim of this study was to investigate the effect of pomelo pulp on the pharmacokinetics of cyclosporine in healthy male Thai volunteers. The study design was an open-label, randomized, single dose, crossover study with a 2-week washout period. A single oral dose of 2 × 100 mg cyclosporine was administered with 200 mL of water. Each subject received 250 g of pomelo pulp or 250 mL of water 1 hour before drug administration and once again 10 minutes following drug administration. Blood samples were collected over a 24 hour period. The point estimates (90% confidence intervals) of the test/control ratio using logarithmic transformed data for the area under the curve (AUC) for blood concentration from time 0 to infinity (AUC(0- ∞)) and the observed maximum concentration (C(max)) were 128.8% (120.6-137.6) and 136.1% (126.0-146.8), respectively. These 90% confidence intervals were higher than the accepted bioequivalence range defined by the European Medicines Agency guidelines for narrow therapeutic index drugs (90%-111% for AUC and 80%-125% for C(max)). However, the apparent terminal half-life (t(1/2)) was not significantly different. In conclusion, co-administration of cyclosporine and pomelo pulp increased the relative bioavailability of cyclosporine. PMID:25408261

  9. 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

  10. Reassessment of stiripentol pharmacokinetics in healthy adult volunteers.

    PubMed

    Peigné, Sophie; Rey, Elisabeth; Le Guern, Marie-Emmanuelle; Dulac, Olivier; Chiron, Catherine; Pons, Gerard; Jullien, Vincent

    2014-07-01

    Because children who have been receiving stiripentol for the treatment of Dravet syndrome for more than 10 years are now becoming young adults, it is important to accurately characterize stiripentol pharmacokinetics in this age range. A double-blind placebo-controlled dose ranging study was therefore conducted to investigate the pharmacokinetics and tolerability of stiripentol in 12 healthy volunteers. Each subject received 3 single doses of stiripentol (500, 1000, and 2000 mg) separated by a wash-out period of 1 week. Pharmacokinetics of stiripentol was analyzed for each dose by non-compartmental analysis. Median area under the curve (AUC), terminal elimination half-life (t1/2,z) and maximal concentration (Cmax) were calculated for between-dose comparison. Safety was evaluated based on both clinical and biological criteria. Oppositely to previous results, there was no concentration rebounds in the elimination phase, which could be the consequence of the food intake. A more than proportional increase in the AUC was observed, associated with a significant increase in the t1/2,z, for increasing doses (median AUC of 8.3, 31 and 88 mgh/L, and median t1/2,z of 2, 7.7 and 10h for the 500, 1000, and 2000 mg doses respectively), which confirmed the Michaelis-Menten pharmacokinetics of Stiripentol. However, dose-normalized Cmax did not significantly vary between doses. Median Michaelis-Menten parameters were 117 mg/h for Vmax and 1.9 mg/L for Km. No safety concern was observed during the study. The present study allowed a better characterization of the disposition phase of stiripentol and confirmed its non-linear pharmacokinetic behaviour. Further pharmacokinetic/pharmacodynamic studies would be useful to determine the optimal dose of stiripentol for the treatment of Dravet patients in adulthood. PMID:24725808

  11. Doxapram Only Slightly Reduces the Shivering Threshold in Healthy Volunteers

    PubMed Central

    Komatsu, Ryu; Sengupta, Papiya; Cherynak, Grigory; Wadhwa, Anupama; Sessler, Daniel I.; Liu, Jin; Hurst, Harrell E.; Lenhardt, Rainer

    2005-01-01

    We determined the effects of doxapram on the major autonomic thermoregulatory responses in humans. Nine healthy volunteers were studied on two days: Control and Doxapram (intravenous infusion to a plasma concentration of 2.4 ±0.8 μg/mL, 2.5 ±0.9 μg/mL, and 2.6 ±1.1 μg/mL at the sweating, vasoconstriction, and shivering thresholds, respectively). Each day, skin and core temperatures were increased to provoke sweating, then reduced to elicit peripheral vasoconstriction and shivering. We determined the sweating, vasoconstriction, and shivering thresholds with compensation for changes in skin temperature. Data were analyzed with paired t tests and presented as means ± SDs; P < 0.05 was considered statistically significant. Doxapram did not change the sweating (Control: 37.5±0.4°C, Doxapram: 37.3±0.4°C, P=0.290) or the vasoconstriction threshold (36.8±0.7 vs. 36.4±0.5°C; P=0.110). However, it significantly reduced the shivering threshold from 36.2±0.5 to 35.7±0.7°C (P=0.012). No sedation or symptoms of panic were observed on either study day. The observed reduction in the shivering threshold explains the drug's efficacy for treatment of postoperative shivering; however, a reduction of only 0.5°C is unlikely to markedly facilitate induction of therapeutic hypothermia as a sole agent. PMID:16243996

  12. 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

  13. Cardiopulmonary interactions of salbutamol and hypoxaemia in healthy young volunteers.

    PubMed Central

    Kiely, D G; Cargill, R I; Lipworth, B J

    1995-01-01

    1. Nebulised salbutamol is frequently used in the treatment of asthma and chronic obstructive pulmonary disease. Its effects on the cardiovascular system have been extensively investigated although as yet little is known concerning its effects on the pulmonary circulation, particularly during hypoxaemia. We have therefore examined the effects of nebulised salbutamol on pulmonary haemodynamics to see if it modifies hypoxic pulmonary vasoconstriction. 2. Eight healthy normal volunteers were studied on two separate occasions. After resting to achieve baseline haemodynamics patients were randomised to receive 5 mg salbutamol or placebo via a nebuliser. They were restudied after 30 min and then rendered hypoxaemic by breathing an N2/O2 mixture to achieve an SaO2 of 75-80%. Doppler echocardiography was used to measure mean pulmonary artery pressure (MPAP), cardiac output (CO) and hence pulmonary vascular resistance (PVR). 3. Treatment with salbutamol significantly increased MPAP during normoxaemia and hypoxaemia compared with placebo at 12.0 +/- 1.2 vs 8.0 +/- 0.7 mm Hg and 28.6 +/- 0.9 vs 25.2 +/- 1.0 mm Hg, respectively (P < 0.05). Salbutamol caused a significant increase in heart rate compared with placebo and effects were additive to those of hypoxia at 74 +/- 2 vs 67 +/- 3 beats min-1 during normoxaemia and 84 +/- 3 vs 77 +/- 4 beats min-1 during hypoxaemia, respectively (P < 0.05). Whilst systemic vascular resistance fell in response to salbutamol, PVR was unchanged by salbutamol during either normoxaemia or hypoxaemia. Cardiac output was increased by salbutamol and by hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8554932

  14. Characterization of Physiologic (18)F FSPG Uptake in Healthy Volunteers.

    PubMed

    Mosci, Camila; Kumar, Meena; Smolarz, Kamilla; Koglin, Norman; Stephens, Andrew W; Schwaiger, Markus; Gambhir, Sanjiv S; Mittra, Erik S

    2016-06-01

    Purpose To evaluate the normal biodistribution and kinetics of (S)-4-(3-[18F]fluoropropyl)-l-glutamic acid ((18)F FSPG) in healthy volunteers and to compare (18)F FSPG mean and maximum standardized uptake values (SUVmean and SUVmax, respectively) with those of (18)F fluorodeoxyglucose (FDG) across a variety of organs. Materials and Methods This protocol was reviewed and approved by all appropriate regulatory authorities. An 8-mCi (±10%) dose of (18)F FSPG was given to five subjects (three women, two men), and seven whole-body positron emission tomography (PET) scans were performed 5, 10, 20, 30, 45, 150, and 240 minutes after injection. Regions of interest were analyzed on the resultant (18)F FSPG images to evaluate the kinetics of this radiotracer. The images obtained 45 minutes after injection were used to measure SUVmean and SUVmax in additional regions of the body. These values were compared with similar values obtained with (18)F FDG PET published previously. Descriptive statistics, including average and standard deviation across the five subjects, were used. (18)F FSPG SUVmean and SUVmax were compared. Results On the (18)F FSPG images obtained 45 minutes after injection, there was only low-grade background activity in the majority of analyzed regions. Prominent activity was seen throughout the pancreas. Clearance of the radiotracer through the kidneys and collection in the bladder also were seen. SUV quantification shows notable differences between (18)F FSPG and (18)F FDG in the pancreas ((18)F FSPG SUVmean, 8.2; (18)F FDG SUVmean, 1.3), stomach ((18)F FSPG SUVmax, 3.6; (18)F FDG SUVmax, 1.6), and brain ((18)F FSPG SUVmean, 0.08; (18)F FDG SUVmean, 7.8). The kinetic data showed rapid clearance of the radiotracer from the blood pool and most organs, except the pancreas. Conclusion (18)F FSPG is a PET radiopharmaceutical characterized by rapid clearance from most healthy tissues, except the pancreas and kidneys. A consistent biodistribution pattern was

  15. The pharmacokinetic characters of simvastatin after co-administration with Shexiang Baoxin Pill in healthy volunteers' plasma.

    PubMed

    Tao, Jianfei; Jiang, Peng; Peng, Chengcheng; Li, Min; Liu, Runhui; Zhang, Weidong

    2016-07-15

    To investigate the effect of Shexiang Baoxin Pill (SBP), a tranditional Chinese medicine, on the pharmacokinetic (PK) parameters of simvastatin in healthy volunteers' plasma, a quantitative method was developed using an Agilent G6410A rapid performance liquid chromatography (RPLC) coupled with triple quadrupole mass spectrometry system. The established method was rapid with high extraction recovery and successfully applied for the determination of simvastatin in plasma of 16 healthy volunteers. The results demonstrated that the MRT(0-∞), T1/2 and Tmax value of simvastatin were significantly decreased, while the AUC(0-t) and Cmax values of smivastatin were increased by SBP. The pharmacokinetic study demonstrated that the metabolism parameters of simvastatin could be affected by SBP and the potential drug-drug interaction should be noted in the future clinical practice. PMID:26830535

  16. More than the money: A review of the literature examining healthy volunteer motivations

    PubMed Central

    Stunkel, Leanne; Grady, Christine

    2016-01-01

    Background and Objective Few existing data report the motivations of healthy volunteers in clinical research trials. Some worry that volunteers consider only financial motivations. This study summarized and analyzed existing empirical research on self-reported motivations of healthy volunteers participating in studies not intended to offer benefit from participation. Study Selection A systematic PubMed search was conducted. Inclusion criteria captured English-language empirical studies on the self-reported motivations, reasons, or factors influencing the decision of healthy volunteers to enroll in clinical research. Twelve studies involving more than 2000 healthy volunteers met the criteria and were included in this review. Data Extraction Independent review by the authors and extraction of information about the sample, methodology and objective of the motivations study, description of the clinical trial and whether participation was actual or hypothetical, reported primary and secondary motivations of the healthy volunteers, risk evaluation, and reported differences in motivations related to sociodemographic variables. Results This review showed that although financial reward is the primary motivation for healthy volunteers to participate in clinical trials, financial motivations are one among many other reported motivations, including contributing to science or the health of others, accessing ancillary healthcare benefits, scientific interest or interest in the goals of the study, as well as meeting people and curiosity. Volunteers consider risk when making a decision about participation. Conclusions Although financial incentives are important in recruiting healthy volunteers, their motivations are not limited to financial motivations. Further research is needed to examine motivations in different contexts and countries, the decision making of healthy volunteers, and the dynamics of repeat participation. PMID:21146635

  17. Pharmacokinetics of Lidocaine Hydrochloride Metabolized by CYP3A4 in Chinese Han Volunteers Living at Low Altitude and in Native Han and Tibetan Chinese Volunteers Living at High Altitude.

    PubMed

    Zhang, Juanling; Zhu, Junbo; Yao, Xingchen; Duan, Yabin; Zhou, Xuejiao; Yang, Meng; Li, Xiangyang

    2016-01-01

    To investigate the pharmacokinetics of lidocaine hydrochloride metabolized by cytochrome P450 3A4 (CYP3A4) in Chinese Han volunteers living at low altitude (LA) and in native Han and Tibetan Chinese volunteers living at high altitude, lidocaine hydrochloride 10 mg was given by intramuscular injection to 3 groups: Han volunteers living at LA, and native Han and Tibetan volunteers living at a high altitude. Blood samples were collected before the (baseline) study drug was given and at 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0 h after study drug administration. Lidocaine hydrochloride in plasma was determined by RP-HPLC. Pharmacokinetics parameters of lidocaine hydrochloride showed that there were no significant difference between the native Han and Tibetan volunteers, but the t1/2 was 29.8 and 29.8% higher in 2 groups, respectively, than in the LA group. To study related mechanism, the effects of exposure to chronic high-altitude hypoxia (CHH) on the activity and expression of CYP3A1 were examined in rats. Rats were divided into LA, chronic moderate altitude hypoxia, and CHH groups. CHH caused significant decreases in the activity and protein and mRNA expression of rat CYP3A1 in vivo. This study found significant changes in the disposition of lidocaine hydrochloride in native healthy Tibetan and Han Chinese subjects living at a high altitude in comparison to healthy Han Chinese subjects living at LA, it might be due to significant decreases in the activity and protein and mRNA expression of CYP3A4 under CHH condition. PMID:26730802

  18. Comparative bioavailability study of two brands of prazosin-containing tablets in healthy volunteers.

    PubMed

    Guelen, P J; Janssen, T J; Lam, M H; Vree, T B; Exler, P S

    1990-10-19

    The bioavailability of two prazosin formulations was studied in 12 healthy volunteers. 1 Subject left the study. Based on the statistical tests of the pharmacokinetic parameters of prazosin in 11 volunteers, such as t 1/2, Cmax, tmax and AUC, it could be concluded that both preparations had comparable bioavailabilities. PMID:2255586

  19. CONCENTRATED AMBIENT AIR PARTICLES INDUCE PULMONARY INFLAMMATION IN HEALTHY HUMAN VOLUNTEERS

    EPA Science Inventory


    We tested the hypothesis that exposure of healthy volunteers to concentrated ambient particles (CAPS) is associated with an influx of inflammatory cells into the lower respiratory tract. Thirty-eight volunteers were exposed to either filtered air or particles concentrated fro...

  20. 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...

  1. Payment to healthy volunteers in clinical research: the research subject's perspective.

    PubMed

    Czarny, M J; Kass, N E; Flexner, C; Carson, K A; Myers, R K; Fuchs, E J

    2010-03-01

    Although there is much discussion regarding the ethics of making payments to healthy volunteers for participating in clinical research, little data are available from the point of view of the volunteers as to what they would consider to be fair payment. The objectives of this study were to determine healthy volunteers' estimates of appropriate payments for participation in hypothetical clinical trials in order to explore the reasoning behind these estimates and to examine the association between volunteer demographics and payment expectations. Sixty participants with previous experience as healthy volunteers in research studies were presented with four hypothetical studies and interviewed about their impressions of burden and risks involved in the studies. They were also asked to estimate an appropriate payment to the volunteers for each of the studies. For each of the studies, the payment estimates made by the participants varied over a wide range. However, each individual tended to be consistent in estimate placement within this range. No demographic factor was significantly associated with the estimated study payment. Subjects frequently mentioned risk and logistical burden as factors that should determine payment levels. Healthy volunteer subjects appear to have individualized yet consistent methods of arriving at estimates of payments for participating in clinical studies. These estimates are based on each subject's perception of study burden and associated risk. PMID:20090675

  2. The Volunteer Satisfaction Index: A Validation Study in the Chinese Cultural Context

    ERIC Educational Resources Information Center

    Wong, Lok Ping; Chui, Wing Hong; Kwok, Yan Yuen

    2011-01-01

    Using a Hong Kong-sourced sample of 261 participants, this study set out to validate the Volunteer Satisfaction Index (VSI) in the Chinese cultural context and to evaluate its psychometric properties. The VSI was originally developed by Galindo-Kuhn and Guzley (2001) to measure the outcomes of volunteer experiences. In this study, exploratory…

  3. Giving monoclonal antibodies to healthy volunteers in phase 1 trials: is it safe?

    PubMed Central

    Tranter, Elizabeth; Peters, Gary; Boyce, Malcolm; Warrington, Steve

    2013-01-01

    Many monoclonal antibodies (MAbs) have been studied in healthy volunteers in phase 1, but few data have been published on the safety of that practice. We aimed to review the available data, and thereby to estimate the risks of participation in phase 1 trials of MAbs. We searched PubMed, the ClinicalTrials.gov database and Google, using the search terms ‘monoclonal antibody’, ‘phase 1’ and ‘healthy volunteers’. We identified 70 completed trials of MAbs in healthy volunteers, but the published data were too sparse to allow confident assessment of the risks of MAbs in healthy volunteers. Our best estimate of risk of a life-threatening adverse event was between 1 : 425 and 1 : 1700 volunteer-trials, but all such events occurred in a single trial (of TGN1412). In a phase 1 trial of a small molecule, the risk of death or a life-threatening adverse event appears to be 1 : 100 000–1 000 000 volunteer-trials, which is similar to the risk of many ordinary daily activities. Most people would consider that level of risk to be ‘minimal’ or ‘negligible’ and, therefore, acceptable. On that basis, the safety record of MAbs in healthy volunteers has been ruined by the TGN1412 disaster. However, that experience is unlikely to be repeated, because of improvements in governance and practice of phase 1 trials. If the experience of TGN1412 is disregarded, it seems reasonable to continue using healthy volunteers in phase 1 trials of MAbs, provided that there are scientific and medical reasons to conclude that the risk is truly minimal. PMID:23438102

  4. 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

  5. Pharmacokinetic and Pharmacodynamic Modeling Analysis of Intravenous Esomeprazole in Healthy Volunteers.

    PubMed

    Liu, Dongyang; Yang, Hong; Jiang, Ji; Nagy, Péter; Shen, Kai; Qian, Jiaming; Hu, Pei

    2016-07-01

    Esomeprazole is one of the most commonly used drugs to treat gastroesophageal reflux disease and peptic ulcers, but the quantitative relationships among the pharmacokinetics (PK), pharmacodynamics (PD), and pharmacogenomics (PG) of the drug are not fully understood in special patient populations. A clinical PK/PD/PG study of intravenous (IV) esomeprazole in 5 dosing regimens was conducted in 20 healthy Chinese volunteers, who were categorized into Helicobacter pylori (HP)-negative and HP-positive subgroups. Plasma esomeprazole concentration and intragastric H(+) concentration were monitored for 24 hours postdosing. Population PK (PopPK) models were tested based on elimination characteristics and other data. For a single-dose IV esomeprazole regimen, a 2-compartment model with nonlinear elimination characteristics fitted the PK data well. The elimination of esomeprazole was found to be significantly linked to CYP2C19 genotype by 11% to 29%. A mechanism-based PD model was first tested to mimic the irreversible inhibition of H(+) /K(+) -ATPase by esomeprazole using a cell-killing mechanism and models of gastric H(+) secretion that included the effects of an asymmetric circadian rhythm and food effects. Results from this PD model showed that the turnover rate of H(+) /K(+) -ATPase was significantly different between HP-negative and HP-positive subgroups. In conclusion, the PopPK model quantitatively identified the effects of the CYP2C19 genotype on esomeprazole elimination in healthy subjects for the first time. In addition, the effects of HP status on drug effect, H(+) /K(+) -ATPase turnover, and circadian rhythm amplitude were preliminarily explored using a mechanism-based PD model. PMID:26970404

  6. Effects of obeticholic acid on lipoprotein metabolism in healthy volunteers.

    PubMed

    Pencek, R; Marmon, T; Roth, J D; Liberman, A; Hooshmand-Rad, R; Young, M A

    2016-09-01

    The bile acid analogue obeticholic acid (OCA) is a selective farnesoid X receptor (FXR) agonist in development for treatment of several chronic liver diseases. FXR activation regulates lipoprotein homeostasis. The effects of OCA on cholesterol and lipoprotein metabolism in healthy individuals were assessed. Two phase I studies were conducted to evaluate the effects of repeated oral doses of 5, 10 or 25 mg OCA on lipid variables after 14 or 20 days of consecutive administration in 68 healthy adults. Changes in HDL and LDL cholesterol levels were examined, in addition to nuclear magnetic resonance analysis of particle sizes and sub-fraction concentrations. OCA elicited changes in circulating cholesterol and particle size of LDL and HDL. OCA decreased HDL cholesterol and increased LDL cholesterol, independently of dose. HDL particle concentrations declined as a result of a reduction in medium and small HDL. Total LDL particle concentrations increased because of an increase in large LDL particles. Changes in lipoprotein metabolism attributable to OCA in healthy individuals were found to be consistent with previously reported changes in patients receiving OCA with non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. PMID:27109453

  7. Experimental manipulations of pain catastrophizing influence pain levels in patients with chronic pain and healthy volunteers.

    PubMed

    Kjøgx, Heidi; Kasch, Helge; Zachariae, Robert; Svensson, Peter; Jensen, Troels S; Vase, Lene

    2016-06-01

    Pain catastrophizing (PC) has been related to pain levels in both patients experiencing acute or chronic pain and in healthy volunteers exposed to experimental pain. Still, it is unclear whether high levels of pain catastrophizing lead to high levels of pain or vice versa. We therefore tested whether levels of pain catastrophizing could be increased and decreased in the same participant through hypnotic suggestions and whether the altered level of situation-specific pain catastrophizing was related to increased and decreased pain levels, respectively. Using the spontaneous pain of 22 patients with chronic tension-type headache and experimentally induced pain in 22 healthy volunteers, participants were tested in 3 randomized sessions where they received 3 types of hypnotic suggestions: Negative (based on the 13 items in the Pain Catastrophizing Scale), Positive (coping-oriented reversion of the Pain Catastrophizing Scale), and Neutral (neutral sentence) hypnotic suggestions. The hypnotic suggestions significantly increased and decreased situation-specific PC in both patients and healthy volunteers (P < 0.001). Also, the levels of pain intensity and pain unpleasantness were significantly altered in both patients and healthy volunteers (P < 0.001). Furthermore, regression analyses showed that changes in pain catastrophizing predicted changes in pain in patients (R = 0.204-0.304; P < 0.045) and in healthy volunteers (R = 0.328-0.252; P < 0.018). This is the first study to successfully manipulate PC in positive and negative directions in both patients with chronic pain and healthy volunteers and to show that these manipulations significantly influence pain levels. These findings may have important theoretical and clinical implications. PMID:26871534

  8. 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

  9. Platelet activation during angiotensin II infusion in healthy volunteers.

    PubMed

    Larsson, P T; Schwieler, J H; Wallén, N H

    2000-01-01

    The present study was undertaken to evaluate the effects of an intravenous infusion of angiotensin II (10 ng/kg per min) on platelet function and coagulation in vivo in 18 healthy males. The infusion increased mean arterial pressure by 23+/-2 mm Hg. Plasma beta-thromboglobulin levels, reflecting platelet secretion, increased by 66+/-24% during the infusion, as did also platelet surface expression of P-selectin as measured by flow cytometry. Platelet fibrinogen binding increased, whereas platelet aggregability, assessed by ex vivo filtragometry, was unaltered. Angiotensin II caused mild activation of the coagulation cascade with increases in plasma levels of thrombin-antithrombin complex and prothrombin fragment F1 + 2. In conclusion, angiotensin II has mild platelet-activating effects in vivo and also enhances coagulation. Markers of platelet secretion are significantly increased, whereas markers of platelet aggregability are less affected. The clinical relevance of these findings remains to be clarified. PMID:10691100

  10. Increased set shifting costs in fasted healthy volunteers.

    PubMed

    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

  11. 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

  12. Absolute bioavailability and regional absorption of ticagrelor in healthy volunteers

    PubMed Central

    Teng, Renli; Maya, Juan

    2014-01-01

    Objective Ticagrelor is a direct-acting, reversibly-binding, oral P2Y12 receptor antagonist. It demonstrates predictable, linear pharmacokinetics. Two studies were undertaken to further elucidate the absolute bioavailability of ticagrelor and its regional absorption in the gastrointestinal (GI) tract. Design and methods In two open-label, randomized, cross-over studies, 12 volunteers received a single dose of ticagrelor: oral 90 mg and 15 mg IV (Study 1); or 100 mg oral suspension vs 100 mg immediate release (IR) tablet (Study 2). After the initial cross-over period in Study 2, patients received 100 mg suspension delivered to specific sites in the GI tract using an Enterion capsule. In both studies, plasma concentrations of ticagrelor and AR-C124910XX were measured following administration of each formulation. Results The mean absolute bioavailability of ticagrelor was 36% (95% confidence interval = 30–42%). Metabolite:parent ratios were higher after oral administration, compared with IV administration (maximum plasma concentration [Cmax] = 0.356 and 0.037; area under the plasma concentration-time curves [AUC] = 0.530 and 0.173, respectively). Following oral administration of the 100 mg IR tablet, the AUC and Cmax of ticagrelor were 78% and 58%, respectively, of those following oral administration of the 100 mg suspension. Exposure to ticagrelor decreased the further down the GI tract it was released: mean Cmax for ticagrelor was 91%, 68%, and 13% that for the oral suspension when released in the proximal small bowel, distal small bowel and ascending colon, respectively; mean AUCs were 89%, 73%, and 32%, respectively. Conclusion The mean absolute bioavailability of ticagrelor was 36% and the proportion of ticagrelor absorbed decreased the further down the GI tract it was released: the mean AUC for ticagrelor was 89% (proximal small bowel), 73% (distal small bowel), and 32% (ascending colon) that of the mean AUC for the orally

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

    PubMed Central

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

    2015-01-01

    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

  14. 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

  15. 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

  16. 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...

  17. Quantitative Analysis of Cerebrospinal Fluid Pressure Gradients in Healthy Volunteers and Patients with Normal Pressure Hydrocephalus

    PubMed Central

    HAYASHI, Naokazu; MATSUMAE, Mitsunori; YATSUSHIRO, Satoshi; HIRAYAMA, Akihiro; ABDULLAH, Afnizanfaizal; KURODA, Kagayaki

    2015-01-01

    Magnetic resonance imaging (MRI) can depict not only anatomical information, but also physiological factors such as velocity and pressure gradient. Measurement of these physiological factors is necessary to understand the cerebrospinal fluid (CSF) environment. In this study we quantified CSF motion in various parts of the CSF space, determined changes in the CSF environment with aging, and compared CSF pressure gradient between patients with idiopathic normal pressure hydrocephalus (iNPH) and healthy elderly volunteers. Fifty-seven healthy volunteers and six iNPH patients underwent four-dimensional (4D) phase-contrast (PC) MRI. CSF motion was observed and the pressure gradient of CSF was quantified in the CSF space. In healthy volunteers, inhomogeneous CSF motion was observed whereby the pressure gradient markedly increased in the center of the skull and gradually decreased in the periphery of the skull. For example, the pressure gradient at the ventral surface of the brainstem was 6.6 times greater than that at the convexity of the cerebrum. The pressure gradient was statistically unchanged with aging. The pressure gradient of patients with iNPH was 3.2 times greater than that of healthy volunteers. The quantitative analysis of 4D-PC MRI data revealed that the pressure gradient of CSF can be used to understand the CSF environment, which is not sufficiently given by subjective impression of the anatomical image. PMID:26226976

  18. Calcium carbonate does not affect imatinib pharmacokinetics in healthy volunteers

    PubMed Central

    Tawbi, Hussein; Christner, Susan M.; Lin, Yan; Johnson, Matthew; Mowrey, Emily T.; Cherrin, Craig; Chu, Edward; Lee, James J.; Puhalla, Shannon; Stoller, Ronald; Appleman, Leonard R.; Miller, Brian M.; Beumer, Jan H.

    2013-01-01

    Purpose Imatinib mesylate (Gleevec®/Glivec®), has revolutionized the treatment of chronic myeloid leukemias (CML) and gastrointestinal stromal tumors (GIST), and there is evidence for an exposure response relationship. Calcium carbonate is increasingly used as a calcium supplement and in the setting of gastric upset associated with imatinib therapy. Calcium carbonate could conceivably elevate gastric pH and complex imatinib, thereby influencing imatinib absorption and exposure. We aimed to evaluate whether use of calcium carbonate has a significant effect on imatinib pharmacokinetics. Methods Eleven healthy subjects were enrolled in a 2-period, open-label, single-institution, randomized cross-over, fixed-schedule study. In one period, each subject received 400 mg of imatinib p.o.. In the other period, 4000 mg calcium carbonate (Tums Ultra®) was administered p.o. 15 min before 400 mg of imatinib. Plasma concentrations of imatinib and its active N-desmethyl metabolite CGP74588 were assayed by LC-MS; data were analyzed non-compartmentally, and compared after log transformation. Results Calcium carbonate administration did not significantly affect the imatinib area under the plasma concentration versus time curve (AUC) (41.2 μg/mL•h alone versus 40.8 μg/mL•h with calcium carbonate, P=0.99), maximum plasma concentration (Cmax) (2.35 μg/mL alone versus 2.39 μg/mL with calcium carbonate, P=0.89). Conclusions Our results indicate that the use of calcium carbonate does not significantly affect imatinib pharmacokinetics. PMID:24170263

  19. 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

  20. Comparative Pharmacokinetics of Levofloxacin in Healthy Volunteers and in Patients Suffering from Typhoid Fever

    PubMed Central

    Usman, Muhammad; Ashraf, Muhammad; Khokhar, Muhammad Imran; Ashiq, Bilal; Masood, Muhammad Irfan; Afzal, Shehryar; Omer, Ovais; Ali, Mohsin; Qadir, M. Imran

    2013-01-01

    The aim of this study was to characterize the effect of typhoid fever on pharmacokinetic parameters of levofloxacin (LF) and compare the pharmacokinetic parameters of the said antibiotic in healthy human volunteers and patients with typhoid fever. Total of 12 subjects were divided into two groups “A” (healthy volunteers) and “B” (typhoid patients). Single oral dose of LF 500 mg was given and 5 mL of blood was collected from each subject at 0, 0.25, 0.5, 1, 2, 3, 6, 12, 24, 36 and 72 h. Plasma concentrations of LF were measured by HPLC. Pharmacokinetic parameters were calculated from plasma concentration-time data by using MW/PHARM pharmacological analysis. In healthy volunteers, the average pharmacokinetic parameters were as Cmax (6.79 μg/mL), Tmax (1.84 h), T½ (10.03 h), Ka (2.23 h-1), AUC (110.09 μgh/mL), Vd (85.84 L), Cl (4.57 L/h) and in typhoid patients were Cmax (6.90 μg/mL), Tmax (1.82 h), T½ (9.42 h), Ka (2.21 h-1), AUC (105.55 μgh/mL), Vd (64.31 L), Cl (4.75 L/h). The difference between pharmacokinetic parameters of LF in healthy human volunteers and typhoid patients was calculated by using unpaired t-test. As the p-value in case of all pharmacokinetic parameters was more than 0.05, the difference between pharmacokinetic parameters in both healthy human volunteers and typhoid patients was insignificant. It is concluded that there is no need to adjust the dose of LF in typhoid patients. PMID:24250583

  1. Safety Evaluation of Crocin (a constituent of saffron) Tablets in Healthy Volunteers

    PubMed Central

    Mohamadpour, Amir Houshang; Ayati, Zahara; Parizadeh, Mohammad–Reza; Rajbai, Omid; Hosseinzadeh, Hossein

    2013-01-01

    Objective(s): Crocin is the chemical ingredient primarily responsible for the color of saffron. It has different pharmacological effects such as antioxidant, anticancer and memory improving activities. Crocin tablets were evaluated for short-term safety and tolerability in healthy adult volunteers. Materials and Methods: The study was a randomized, double-blind, placebo-controlled design consisting of one month treatment of crocin tablets. Volunteers who fulfilled inclusion and exclusion criteria were randomized into 2 groups of 22 each (males and females) and received 20 mg crocin tablets or placebo. General measures of health were recorded during the study such as hematological, biochemical, hormonal and urinary parameters in pre and post-treatment periods. Results: No major adverse events were reported during the trial. Crocin tablets did not change the above parameters except that it decreased amylase, mixed white blood cells and PTT in healthy volunteers after one month. Conclusion: This clinical safety evaluation showed a relatively safe and normal profile for crocin in healthy volunteers at the given doses within the trial period. PMID:23638291

  2. 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. PMID:23645945

  3. Effect of natriuretic peptides on cerebral artery blood flow in healthy volunteers.

    PubMed

    Guo, Song; Goetze, Jens P; Jeppesen, Jørgen L; Burnett, John C; Olesen, Jes; Jansen-Olesen, Inger; Ashina, Messoud

    2015-12-01

    The natriuretic peptides (NPs), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), have vasoactive functions that concern humans and most animals, but their specific effects on cerebral circulation are poorly understood. We therefore examined the responsiveness of cerebral arteries to different doses of the natriuretic peptides in animals and humans. We conducted a dose-response experiment in guinea pigs (in vitro) and a double-blind, three-way cross-over study in healthy volunteers (in vivo). In the animal experiment, we administered cumulative doses of NPs to pre-contracted segments of cerebral arteries. In the main study, six healthy volunteers were randomly allocated to receive two intravenous doses of ANP, BNP or CNP, respectively, over 20 min on three separate study days. We recorded blood flow velocity in the middle cerebral artery (VMCA) by transcranial Doppler. In addition, we measured temporal and radial artery diameters, headache response and plasma concentrations of the NPs. In guinea pigs, ANP and BNP but not CNP showed significant dose-dependent relaxation of cerebral arteries. In healthy humans, NP infusion had no effect on mean VMCA, and we found no difference in hemodynamic responses between the NPs. Furthermore, natriuretic peptides did not affect temporal and radial artery diameters or induce headache. In conclusion, natriuretic peptides in physiological and pharmacological doses do not affect blood flow velocity in the middle cerebral artery or dilate extracerebral arteries in healthy volunteers. PMID:26417835

  4. 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. PMID:26428276

  5. 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

  6. 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…

  7. Effect of banana on cold stress test & peak expiratory flow rate in healthy volunteers.

    PubMed

    Sarkar, C; Bairy, K L; Rao, N M; Udupa, E G

    1999-07-01

    The effect of banana on cold stress induced hypertension, peak expiratory flow rate and plasma ACE activity in healthy human volunteers was tested. Systolic blood pressure (P < 0.005), diastolic blood pressure (P < 0.025) and mean arterial blood pressure (P < 0.005) were significantly decreased during cold stress after banana treatment compared to controls subjected to cold stress. There was no significant changes in heart rate and peak expiratory flow rate but only significant decrease in plasma ACE activity after banana treatment. Banana decreased the rise of systolic blood pressure and diastolic blood pressure in healthy volunteers subjected to cold stress test without much effect on heart rate and peak expiratory flow rate. PMID:10709336

  8. Urinary excretion of diazepam metabolites in healthy volunteers and drug users.

    PubMed

    Smith-Kielland, A; Skuterud, B; Olsen, K M; Mørland, J

    2001-05-01

    Urinary excretion profiles of diazepam metabolites were investigated. The subjects were healthy volunteers receiving one single 10-mg dose of diazepam or drug abusers starting a prison sentence. Urinary excretion of metabolites was analysed by immunological screening, liquid chromatography and gas chromatography-mass spectrometry. Relating the metabolite concentration to creatinine concentration in the specimens decreased sample-to-sample variations. In some cases such correction could protect a subject from erroneous accusations of a new intake. PMID:11386610

  9. Dopamine D4 receptor gene polymorphism and personality traits in healthy volunteers.

    PubMed

    Persson, M L; Wasserman, D; Geijer, T; Frisch, A; Rockah, R; Michaelovsky, E; Apter, A; Weizman, A; Jönsson, E G; Bergman, H

    2000-01-01

    An association between long alleles of a variable number tandem repeat (VNTR) polymorphism in the dopamine receptor D4 gene and the extraversion related personality traits Excitement and Novelty Seeking has been reported in healthy subjects. In an attempt to replicate the previous findings, 256 healthy Caucasian volunteers were analysed for a potential relationship between the dopamine receptor D4 exon III VNTR polymorphism and Extraversion as assessed by the Revised Neo Personality Inventory (NEO PI-R). The present study did not yield evidence for an association between Extraversion and the dopamine receptor D4 polymorphism. PMID:11009073

  10. Amino acid metabolism in leg muscle after an endotoxin injection in healthy volunteers.

    PubMed

    Vesali, Rokhsareh F; Klaude, Maria; Rooyackers, Olav; Wernerman, Jan

    2005-02-01

    Decreased plasma amino acid concentrations and increased net release of amino acids from skeletal muscle, especially for glutamine, are common features in critically ill patients. A low dose of endotoxin administered to healthy volunteers was used as a human model for the initial phase of sepsis to study the early metabolic response to sepsis. Six healthy male volunteers were studied in the postabsorptive state. Blood samples from the forearm artery and femoral vein were taken during 4 h before and 4 h after an intravenous endotoxin injection (4 ng/kg body wt). In addition, muscle biopsies from the leg muscle were taken. Plasma concentration of the total sum of amino acids decreased by 19% (P = 0.001) and of glutamine by 25% (P = 0.004) the 3rd h after endotoxin administration. At the same time, muscle concentrations of the sum of amino acids and glutamine decreased by 11% (P = 0.05) and 9% (P = 0.09), respectively. In parallel, the efflux from the leg increased by 35% (P = 0.004) for the total sum of amino acids and by 43% (P = 0.05) for glutamine. In conclusion, intravenous endotoxin administration to healthy volunteers, used as a model for the initial phase of sepsis, resulted in a decrease in plasma amino acid concentrations. At the same time, amino acid concentrations in muscle tissue decreased, whereas the efflux of amino acids from leg skeletal muscle increased. PMID:15367399

  11. Diagnosing Bladder Outlet Obstruction Using Non-invasive Decorrelation-Based Ultrasound Imaging: A Feasibility Study in Healthy Male Volunteers.

    PubMed

    Arif, Muhammad; Idzenga, Tim; van Mastrigt, Ron; de Korte, Chris L

    2015-12-01

    A feasibility study on the applicability of an ultrasound decorrelation method to urinary flow imaging was carried out in 20 healthy male volunteers, to provide a basis for a non-invasive approach to diagnose bladder outlet obstruction. Each volunteer voided five times in a flow meter in standing position. During each voiding, ultrasound radiofrequency frames were acquired transperineally at different flow rates. The results indicated that the decrease in correlation (decorrelation) of ultrasound radiofrequency signals had no unique relation with flow rate, but decreased distinctively with urinary flow velocity. In most of the healthy volunteers, the decorrelation was small because of the low flow velocity. However, because of the different flow velocities in volunteers, the variation in slope between volunteers was statistically significant. Therefore, it is probably possible to use the decorrelation method to differentiate between healthy persons and patients with obstruction. PMID:26403699

  12. Pyrosequencing analysis of the human microbiota of healthy Chinese undergraduates

    PubMed Central

    2013-01-01

    Background Elucidating the biogeography of bacterial communities on the human body is critical for establishing healthy baselines from which to detect differences associated with disease; however, little is known about the baseline bacterial profiles from various human habitats of healthy Chinese undergraduates. Results Using parallel barcoded 454 pyrosequencing targeting on the 16S rRNA gene V3 region, the bacterial diversity of the nasopharynx, saliva, dominant hands, and feces were investigated from 10 healthy Chinese junior boarding undergraduates at Zhejiang University. The participants were 21–24 years of age with a body mass index (BMI) < 24 kg/m2. A total of 156,717 high-quality pyrosequencing reads were obtained for evaluating bacterial diversity, which represented 29,887 unique phylotypes. The overall taxonomic distribution of the 16S rRNA gene-based amplicons demonstrated that these 4 habitats of the human body harbored distinct microbiota and could be divided into different clusters according to anatomic site, while the established patterns of bacterial diversity followed the human body habitat (feces, hands, saliva, and nasopharynx). Although significant inter-individual variation was observed, the healthy microbiota still shared a large number of phylotypes in each habitat, but not among the four habitats, indicating that a core microbiome existed in each healthy habitat. The vast majority of sequences from these different habitats were classified into different taxonmies that became the predominant bacteria of the healthy microbiota. Conclusions We first established the framework of microbial communities from four healthy human habitats of the same participants with similar living environments for the Chinese undergraduates. Our data represent an important step for determining the diversity of Chinese healthy microbiota, and can be used for more large-scale studies that focus on the interactions between healthy and diseases states for young Chinese

  13. 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

  14. 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.

  15. 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

  16. 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

  17. Pharmacokinetics and pharmacodynamics of verapamil following sublingual and oral administration to healthy volunteers.

    PubMed Central

    John, D N; Fort, S; Lewis, M J; Luscombe, D K

    1992-01-01

    1. The pharmacokinetics and pharmacodynamics of verapamil administered via the oral and sublingual routes were compared in a randomised, two-way cross-over study involving six healthy male volunteers. 2. Administered sublingually, a verapamil 40 mg (Securon) crushed tablet produced a significantly higher peak plasma concentration (P less than 0.05), a greater rate of absorption (P less than 0.05), and greater bioavailability (P less than 0.05) when compared with orally administered verapamil 40 mg (Securon). 3. In comparison with oral dosing, PR intervals were significantly (P less than 0.05) prolonged between 30 and 90 min after sublingual verapamil dosing. 4. Correlations between log plasma verapamil concentration and percentage increase in PR interval were greater after sublingual compared with oral dosing in all volunteers. PMID:1389935

  18. Effects of acute CDP-choline treatment on resting state brain oscillations in healthy volunteers.

    PubMed

    Knott, Verner; de la Salle, Sara; Smith, Dylan; Choueiry, Joelle; Impey, Danielle; Smith, Meaghan; Beaudry, Elise; Saghir, Salman; Ilivitsky, Vadim; Labelle, Alain

    2015-03-30

    CDP-choline (cytidine-5'-diphosphocholine) is a phospholipid used to treat cognitive disorders, presumably repairing and maintaining brain cell membranes. Additional mechanisms may include enhanced cholinergic neurotransmission as the α7 nicotinic receptor actions of choline and increased acetylcholine synthesis accompanying CDP-choline administration may modulate brain oscillations underlying cognitive processes. This study utilizes electroencephalographic (EEG) recordings in healthy volunteers to evaluate CDP-choline induction of an oscillatory response profile associated with nicotinic stimulation. Resting state EEG was acquired in 24 male volunteers administered low (500mg) and moderate (1000mg) doses of CDP-choline in a randomized placebo-controlled, crossover trial. Consistent with nicotinic agonist treatment, spectral analysis showed dose-dependent reductions in delta and increases in alpha oscillations, which were also accompanied by decreases in beta and gamma oscillatory activity. These findings support the posit that CDP-choline cognitive enhancement involves multiple mechanisms including facilitated nicotinic cholinergic action. PMID:25700947

  19. 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

  20. A Single Consumption of High Amounts of the Brazil Nuts Improves Lipid Profile of Healthy Volunteers

    PubMed Central

    Colpo, Elisângela; Vilanova, Carlos Dalton de Avila; Medeiros Frescura Duarte, Marta Maria; Farias, Iria Luiza Gomes; Irineu Muller, Edson; Muller, Aline Lima Hermes; Moraes Flores, Erico Marlon; 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. PMID:23840948

  1. Rectal Visceral Sensitivity in Women with Irritable Bowel Syndrome without Psychiatric Comorbidity Compared with Healthy Volunteers

    PubMed Central

    Spetalen, Signe; Sandvik, Leiv; Blomhoff, Svein; Jacobsen, Morten B.

    2009-01-01

    Background. Psychiatric comorbidity and visceral hypersensitivity are common in patients with irritable bowel syndrome (IBS), but little is known about visceral sensitivity in IBS patients without psychiatric disorders. Aim. We wanted to examine rectal visceral sensitivity in IBS patients without comorbid psychiatric disorders, IBS patients with phobic anxiety and healthy volunteers. Methods. A total of thirty-eight female, non-constipated IBS patients without psychiatric disorders and eleven female IBS patients with phobic anxiety were compared to nine healthy women using a barostat double random staircase method. The non-psychiatric patients were divided into those with diarrhoea predominant symptoms and those with alternating stool habits. Results. The IBS patients without psychiatric disorders had normal visceral pressure thresholds. However, in the diarrhoea predominant subgroup, the volume discomfort threshold was reduced while it was unchanged in those with alternating stool habits. The phobic IBS patients had similar thresholds to the healthy volunteers. The rectal tone was increased in the non-psychiatric IBS patients with diarrhoea predominant symptoms and in the IBS patients with phobic anxiety. Conclusions. Non-constipated IBS patients without psychiatric disorders had increased visceral sensitivity regarding volume thresholds but normal pressure thresholds. Our study suggests that the lowered volume threshold was due to increased rectal tone. PMID:19789637

  2. Brain structural correlates of schizotypy and psychosis proneness in a non-clinical healthy volunteer sample.

    PubMed

    Nenadic, Igor; Lorenz, Carsten; Langbein, Kerstin; Dietzek, Maren; Smesny, Stefan; Schönfeld, Nils; Fañanás, Lourdes; Sauer, Heinrich; Gaser, Christian

    2015-10-01

    Schizotypal traits are phenotypic risk factors for schizophrenia, associated with biological changes across a putative schizophrenia spectrum. In this study, we tested the hypothesis that brain structural changes in key brain areas relevant to this spectrum (esp. medial and lateral prefrontal cortex) would vary across different degrees of schizotypal trait expression and/or phenotypic markers of psychosis proneness in healthy non-clinical volunteers. We analysed high-resolution 3Tesla magnetic resonance images (MRI) of 59 healthy volunteers using voxel-based morphometry (VBM), correlating grey matter values to the positive and negative symptom factors of the schizotypal personality questionnaire (SPQ, German version) and a measure of psychosis proneness (community assessment of psychic experiences, CAPE). We found positive correlations between positive SPQ dimension and bilateral inferior and right superior frontal cortices, and positive CAPE dimension and left inferior frontal cortex, as well as CAPE negative dimension and right supplementary motor area (SMA) and left inferior parietal cortex. However, only the positive correlation of the right precuneus with negative schizotypy scores was significant after FWE correction for multiple comparisons. Our findings confirm an effect of schizotypal traits and psychosis proneness on brain structure in healthy subjects, providing further support to a biological continuum model. PMID:26164819

  3. 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. PMID:25283522

  4. 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

  5. Clinical evaluation of purified Shilajit on testosterone levels in healthy volunteers.

    PubMed

    Pandit, S; Biswas, S; Jana, U; De, R K; Mukhopadhyay, S C; Biswas, T K

    2016-06-01

    Purified Shilajit, an Ayurvedic rasayana, was evaluated in healthy volunteers of age between 45 and 55 years for its effect on male androgenic hormone viz. testosterone in a randomised, double-blind, placebo-controlled clinical study at a dose of 250 mg twice a day. Treatment with Shilajit for consecutive 90 days revealed that it has significantly (P < 0.05) increased total testosterone, free testosterone and dehydroepiandrosterone (DHEAS) compared with placebo. Gonadotropic hormones (LH and FSH) levels were well maintained. PMID:26395129

  6. 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

  7. Immunomodulatory Effects of Kimchi in Chinese Healthy College Students: A Randomized Controlled Trial

    PubMed Central

    Lee, Hansongyi; Kim, Do Yeon; Lee, Mi Ae; Jang, Ja-Young

    2014-01-01

    This study examined the potential immunomodulatory effects of Kimchi, a traditional fermented Korean vegetable, in healthy Chinese college students. The four-week clinical-trial (randomized, open-label, prospective, controlled) was followed by a one week wash-out period. Healthy Chinese college students (over 20 years of age with a body mass index of 18.5-23.0 kg/m2) volunteered for this study. Forty-three students were randomly classified into two groups, Kimchi (n = 21, supplemented with 100 g of Kimchi per day) or non-Kimchi (n = 22, supplemented with 100 g of radish per day, control) groups. During the four-week intervention period, students were asked to maintain their usual diet and activity, and instructed not to take any medications, functional food products, or dietary supplements. Anthropometrics, nutritional intake, and blood immune parameters (lymphocyte subsets, cytokines, and immunoglobulins) were measured before and after the four weeks of intervention. Thirty-nine students (19 in the Kimchi group, 20 in the non-Kimchi group) finished the study. After the intervention, no significant changes were observed in lymphocyte subsets (T-cell, B-cell, NK cell), pro-inflammatory cytokines (IL-6, TNF-α), anti-inflammatory cytokines (IL-4 and IL-10), and immunoglobulins (Ig A, G, and M) between groups in either the Kimchi or non-Kimchi. These results suggest that the short-term consumption of Kimchi has no immunomodulatory effects in healthy Chinese college students. PMID:25136537

  8. Immunomodulatory effects of kimchi in chinese healthy college students: a randomized controlled trial.

    PubMed

    Lee, Hansongyi; Kim, Do Yeon; Lee, Mi Ae; Jang, Ja-Young; Choue, Ryowon

    2014-07-01

    This study examined the potential immunomodulatory effects of Kimchi, a traditional fermented Korean vegetable, in healthy Chinese college students. The four-week clinical-trial (randomized, open-label, prospective, controlled) was followed by a one week wash-out period. Healthy Chinese college students (over 20 years of age with a body mass index of 18.5-23.0 kg/m(2)) volunteered for this study. Forty-three students were randomly classified into two groups, Kimchi (n = 21, supplemented with 100 g of Kimchi per day) or non-Kimchi (n = 22, supplemented with 100 g of radish per day, control) groups. During the four-week intervention period, students were asked to maintain their usual diet and activity, and instructed not to take any medications, functional food products, or dietary supplements. Anthropometrics, nutritional intake, and blood immune parameters (lymphocyte subsets, cytokines, and immunoglobulins) were measured before and after the four weeks of intervention. Thirty-nine students (19 in the Kimchi group, 20 in the non-Kimchi group) finished the study. After the intervention, no significant changes were observed in lymphocyte subsets (T-cell, B-cell, NK cell), pro-inflammatory cytokines (IL-6, TNF-α), anti-inflammatory cytokines (IL-4 and IL-10), and immunoglobulins (Ig A, G, and M) between groups in either the Kimchi or non-Kimchi. These results suggest that the short-term consumption of Kimchi has no immunomodulatory effects in healthy Chinese college students. PMID:25136537

  9. Effect of ispaghula husk on the faecal output of bile acids in healthy volunteers.

    PubMed

    Chaplin, M F; Chaudhury, S; Dettmar, P W; Sykes, J; Shaw, A D; Davies, G J

    2000-04-01

    Faecal bile acids are associated with both colorectal cancer and serum cholesterol levels. We investigate whether dosing with ispaghula husk affects the faecal bile acid weights and concentrations in healthy adults. Sixteen healthy volunteers consumed 7.0 g/day ispaghula husk, containing 5.88 g/day Englyst-determinable dietary fibre, for the middle 8 weeks of a 12-week period. Stool samples were collected, analysed for faecal bile acids and their form and dry weight determined. Correlations between the faecal bile acids, the stool parameters and the dietary intake were tested. Ispaghula husk treatment significantly lowers faecal lithocholic and isolithocholic acids and the weighted ratio of lithocholic acids to deoxycholic acid. These effects revert towards their initial states at the end of the treatment period. These changes in the faecal bile acid profiles indicate a reduction in the hydrophobicity of the bile acids in the enterohepatic circulation. PMID:10822018

  10. Renal dopamine excretion in healthy volunteers after oral ingestion of L-dopa.

    PubMed

    Barthelmebs, M; Mbou, P; Stephan, D; Grima, M; Imbs, J L

    1993-01-01

    L-Dopa is converted to dopamine by aromatic-L-amino acid decarboxylase (AADC). In the kidney, proximal tubular epithelial cells are rich in AADC and urinary free dopamine excretion is a marker for endorenal extraneuronal dopamine synthesis. The urinary free dopamine excretion was analysed in a double-blind cross-over study after oral ingestion of L-Dopa or a placebo in five healthy volunteers. The drug ingestions were separated by one week's wash-out. Since in a preliminary study, two volunteers ingesting a single L-Dopa dose of 500 mg with breakfast experienced nausea, the five volunteers of the present study were given 300 mg L-Dopa (50 mg at 9 am with breakfast, 100 mg before lunch and 150 mg before dinner) without any adverse effects. L-Dopa induced an increase in 24-h urinary dopamine excretion (HPLC with electrochemical detection). Free urinary dopamine (1900 micrograms/24 h) accounted for 0.8% of the daily oral L-Dopa dose and represented 10% of total urinary dopamine excretion. L-Dopa treatment had no significant effect on mean ambulatory arterial blood pressure and heart rate measured from 9 am to 6 pm (Spacelabs) or on 24 h urinary water and sodium excretion. PMID:8458598

  11. Impact of injectable cephalosporins on the gastrointestinal microflora: observations in healthy volunteers and hospitalized patients.

    PubMed

    Knothe, H; Dette, G A; Shah, P M

    1985-01-01

    A disturbed microbiological ecosystem of the gut flora is frequently seen as a consequence of antibiotic therapy. Because this impact on the physiological balance is known to be causative for severe nosocomial infections and is mainly seen with antibiotics that are massively excreted via the bile (e.g. broadspectrum penicillins, ceftriaxone and cefoperazone), we investigated cefotaxime (CTX), cefotiam (CTM), cefmenoxime (CMX), ceftazidime (CAZ), ceftizoxime (CZX) and cefazolin + netilmicin (CEZ + NTL) in healthy volunteers. The respective daily i.v. doses, days of medication and numbers of volunteers were: CTX 3 g, 1 d, n = 8; CTM 6 g, 3 d, n = 15; CMX 4 g, 3 d, n = 15; CAZ 4 g, 1 d, n = 8; CZX 4 g, 1 d, n = 8; CEZ + NTL 2 X 3 g + 1 X 3 mg/kg/day, 4 d, n = 15. CTX was also investigated in 11 selected hospitalized patients. One or two stool specimens were taken before, during and several days after medication. The microorganisms were also tested for ampicillin and CEZ resistance on selective media. Ampicillin and CEZ resistance was much higher in hospitalized patients than in volunteers (mainly Proteus and Serratia sp.): 90% vs. 42% and 63.6% vs. 43%, respectively. CTX did not affect the anaerobes (Bacteroides sp. and lactobacilli) that are antagonistic to clostridia and Candida. No selection of strains resistant to ampicillin or CEZ occurred. In hospitalized patients, the level of resistance to these drugs was lower after treatment than before.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:4055042

  12. 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. PMID:23733488

  13. 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

  14. 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. PMID:26351508

  15. Prograf five milligrams versus Tacrolimus medis in healthy volunteers: a bioequivalence study.

    PubMed

    Masri, M; Rizk, S; Boujbel, L; Bellahirich, W; Baassoumi, D; Attia, M; Matha, V

    2013-01-01

    For FDA approval, bioequivalence of a generic version of Tacrolimus must be demonstrated in a randomized, two-treatments, two-periods, two-sequences, single-dose crossover study in healthy adult volunteers. Currently there are at least 3 differents generic equivalent for Tacrolimus, that are approved by the EMA and the FDA, with a USA market share of nearly 50%. However, the market share of generic immunosuppressive drugs in the Middle East region is still very low due to the reluctance of the physician to accept Tacrolimus generics, considered to be a narrow therapeutic window drug, that are approved using the standard bioequivalence criteria of 80% to 125%. Herein we present a bioequivalence study of a new Tacrolimus generic, Tacrolimus Medis 5 mg developed by Medis Tunisia batch number 12G3003 compared with Prograf® 5 mg batch number 7202 manufactured by Astellas Toyama Co., Ltd. Japan and HIKMA Pharmaceuticals, Amman-Jordan in healthy adult volunteers using the 90%-111% criteria recommended for drugs with narrow therapeutic window. The study was, balanced, randomized, two-treatments, two-periods, two-sequences, single dose, crossover, comparative oral bioavailability study in healthy adult human volunteers. The study was carried out in accordance with the Basic Principles defined in the U.S. 21 CFR Part 312.20, the principles enunciated in the Declaration of Helsinki (World Medical Association Declaration of Helsinki). Thirty six non-smoking healthy, as determined by medical history, volunteers, 18 years and older, were included. Following randomization using a computer software (pharma solution) the volunteers were given a single oral dose of 5 milligrams following a 12 hour fast with a wash out period of 7 days. Pharmacokinetics profile with blood levels at: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, and 24 hours were performed following each dose. Tacrolimus plasma level was determined using an HPLC validated method (Transmedical For Life S.A.R.L. Beirut

  16. The effect of cryotherapy on oral mucosa: a study in healthy volunteers.

    PubMed

    Svanberg, Anncarin; Ohrn, Kerstin; Broström, Hans; Birgegård, Gunnar

    2012-12-01

    Oral cryotherapy causes local vasoconstriction, which reduces blood flow and reduces the cytotoxic damage to the oral mucosa, has been shown to reduce oral mucositis after intense cytostatic treatment. The main object of this study was to investigate the effect of oral cryotherapy on the temperature in the oral mucosa, the level of proinflammatory cytokine interleukin-6 (IL-6) in saliva and the effect on blood pressure in healthy volunteers, before and after 1 h of cooling the oral cavity with crushed ice. Twelve healthy volunteers [mean age 32.4 (SD 13.2) (20-56) years] were treated with oral cryotherapy in the form of crushed ice. Temperature measurements were performed in the oral mucosa using infrared thermograph following a flowchart protocol. Blood pressure (BP) was measured with a sphygmomanometer. Saliva was analysed for inflammatory cytokine IL-6, using an enzyme-linked immunosorbent assay (ELISA). All participants fulfilled the cooling session. The temperature in the oral cavity decreased significantly (mean 12.9 °C, p < .002). The systolic BP was marginally but significantly higher after cooling (~5 mmHg, p = .019). We could not detect any differences in cytokine IL-6 levels before and after oral cooling. We conclude that cryotherapy during 1 h lowers the mucosal temperature as much as ~12.9 °C, which explains the significant protective effect against mucosal damage by cytostatic drugs. The cooling caused no increase in IL-6 levels. Systemic blood pressure was marginally increased. PMID:22476810

  17. Ascending-dose study of noribogaine in healthy volunteers: pharmacokinetics, pharmacodynamics, safety, and tolerability.

    PubMed

    Glue, Paul; Lockhart, Michelle; Lam, Fred; Hung, Noelyn; Hung, Cheung-Tak; Friedhoff, Lawrence

    2015-02-01

    Noribogaine is the active metabolite of the naturally occurring psychoactive substance ibogaine, and may help suppress withdrawal symptoms in opioid-dependent subjects. The objectives of this Phase I study were to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of noribogaine. In this ascending single-dose, placebo-controlled, randomized, double-blind, parallel-group study in 36 healthy drug-free male volunteers, 4 cohorts (n = 9) received oral doses of 3, 10, 30, or 60 mg or matching placebo, with intensive safety and pharmacokinetic assessments out to 216 hours, along with pharmacodynamic assessments sensitive to the effects of mu-opioid agonists. Noribogaine was rapidly absorbed, with peak concentrations occurring 2-3 hours after oral dosing, and showed dose-linear increases of area under the concentration-time curve (AUC) and Cmax between 3 and 60 mg. The drug was slowly eliminated, with mean half-life estimates of 28-49 hours across dose groups. Apparent volume of distribution was high (mean 1417-3086 L across dose groups). No safety or tolerability issues were identified in any cohort. No mu-opioid agonist pharmacodynamic effects were noted in pupillometry or cold-pressor testing. Single oral doses of noribogaine 3-60 mg were safe and well tolerated in healthy volunteers. PMID:25279818

  18. Effects of Danshen Ethanol Extract on the Pharmacokinetics of Fexofenadine in Healthy Volunteers

    PubMed Central

    Qiu, Furong; Zeng, Jin; Liu, Songcan; He, Min; Zhu, Leilei; Ye, Yujie; Miao, Ping; Shen, Shujiao; Jiang, Jian

    2014-01-01

    This study investigated the effect of multidose administration of danshen ethanol extract on fexofenadine pharmacokinetics in healthy volunteers. A sequential, open-label, two-period pharmacokinetic interaction design was used. 12 healthy male volunteers received a single oral dose of fexofenadine (60 mg) followed by danshen ethanol extract (1 g orally, three times a day) for 10 days, after which they received 1 g of the danshen extract with fexofenadine (60 mg) on the last day. The plasma concentrations of fexofenadine was measured by LC-MS/MS. After 10 days of the danshen extract administration, the mean AUC and Cmax⁡ of the fexofenadine was decreased by 37.2% and 27.4% compared with the control, respectively. The mean clearance of fexofenadine was increased by 104.9%. The in vitro study showed that tanshinone IIA and cryptotanshinone could induce MDR1 mRNA. This study showed that multidose administration of danshen ethanol extract could increase oral clearance of fexofenadine. The increased oral clearance of fexofenadine is attributable to induction of intestinal P-glycoprotein. PMID:25538791

  19. Pharmacogenetics of quetiapine in healthy volunteers: association with pharmacokinetics, pharmacodynamics, and adverse effects.

    PubMed

    Cabaleiro, Teresa; López-Rodríguez, Rosario; Román, Manuel; Ochoa, Dolores; Novalbos, Jesús; Borobia, Alberto; Carcas, Antonio; Abad-Santos, Francisco

    2015-03-01

    Quetiapine is an atypical antipsychotic used for treatment of schizophrenia. Variability in response to this drug may be associated with pharmacogenetics. The aim of this study was to identify genetic markers related to the pharmacokinetics, pharmacodynamics, and adverse effects of quetiapine. The study population comprised 79 healthy volunteers from two bioequivalence trials who were genotyped to identify polymorphisms in genes encoding enzymes, receptors, and transporters. Quetiapine plasma levels were quantified using high-performance liquid chromatography/mass spectrometry. Prolactin plasma levels were detected by indirect chemiluminescence. Possible adverse effects were recorded throughout the study. Factors with P value of 0.1 or less in the univariate analysis were included in a multiple regression analysis (logistic regression for adverse reactions). The area under the curve and clearance of quetiapine were affected by polymorphisms in CYP1A2 and DRD3, respectively. Men had a lower quetiapine area under the curve compared with women. Prolactin iC(max) was higher in volunteers harboring polymorphisms in CYP2C19 and AGT. An association was detected between polymorphisms in CYP1A1 and CYP2C9 and somnolence. Several polymorphisms are responsible for differences in the pharmacokinetics, pharmacodynamics, and safety of quetiapine in healthy individuals. PMID:25025989

  20. 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

  1. Objective and subjective assessment of digestion after ingestion of an iced dessert in healthy volunteers.

    PubMed

    Garzaro, Massimiliano; Pecorari, G; Nadalin, J; Raimondo, L; Palmo, A; Baccega, M; Giordano, C

    2010-01-01

    The aim of our study is to assess, with objective measures, the impact on digestion of a coffee-flavoured iced dessert ingested at the end of a standardized meal; moreover, a subjective assessment, using a specific questionnaire, was carried out in order to compare objective and subjective data. Ten healthy male volunteers, after ENT and psychological assessment, underwent two scintigraphic evaluations (standardized meal without and with coffee-flavoured iced dessert) and, after the meal, filled in a specific questionnaire named dynamic digestibility questionnaire. In our sample the ingestion of the coffee-flavoured iced dessert seemed to improve the digestibility of a standardized meal: the difference between the curves of gastric emptying without and with iced dessert is statistically significant. These data are strongly confirmed by subjective assessment: the dynamic digestibility questionnaire (DDQ) showed a higher digestibility of a standardized meal with the coffee-flavoured iced dessert in comparison to a normal meal. The current study represents a preliminary report on this topic with a small sample of healthy volunteers: further studies on larger population are requested in order to confirm all the encouraging results herein discussed. PMID:20487635

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. Changing Geomagnetic Field and Heart Rates Variability in Healthy Volunteers: A Pilot Study

    NASA Astrophysics Data System (ADS)

    Jordanova, Malina; Zenchenko, Tatiana; Poskotinova, Lilia; Medvedeva, Anna; Uzunov, Todor; Alenikova, Alexandra

    Space Climate is an interdisciplinary science that deals with the long-term change in the Sun, and its effects in the near-Earth environment, including possible effects on human health. This paper will present the first results from simultaneous experiments performed at 3 different locations - Sofia, Bulgaria 42° 40' N 23° 20' E; Moscow, Russia 55° 45' N 37° 36‘ E and Arkhangelsk, Russia 64° 34' N / 40° 32' E. Subjects are 5 healthy volunteers, women, mean age 39,4 years. The experiments are part of the project “Heliobiology” (2011 - 2015) that reflects the intense interest towards the influence of solar activity and meteorology on the human health. The aim of the experiments is to study the degree of conjugation of the heart rate variability and the variations of the geomagnetic field. To minimize the experimental bias one and the same hard- and software were applied during the testing. ECG signals were recorder via "KARDI-2", the software package is "Ecosan-2007", both developed by "Medical Computer Systems", Zelenograd, Russia. The duration of the observations ranged from 60 to 120 minutes. A comparison of the dynamics of the minute variations of the heart rate with the horizontal components of the geomagnetic field vector revealed a synchronization of some of the research parameters as well as specific individual differences. Despite of the small sample size (5 subjects per 8 measures), in over 70% of the experimental data a similar patterns of variation of geophysical and heart rate variability were recorded. The experiments discussed involved healthy volunteers, i.e. people that have good adaptation reserves, and the response to variation of geomagnetic field will not push them beyond the physiological norms. The observed effect of synchronization of heart rate fluctuations of healthy subjects with fluctuations of geomagnetic field may give an effective tool to address further one especially interesting problems - the mechanism of geomagnetic

  8. Mixed effects of OATP1B1, BCRP and NTCP polymorphisms on the population pharmacokinetics of pravastatin in healthy volunteers.

    PubMed

    Lu, Xue-Feng; Zhou, Yang; Bi, Kai-Shun; Chen, Xiao-Hui

    2016-09-01

    1. Pravastatin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor used for the treatment of hyperlipidaemia. This study aims to investigate the effects of genetic polymorphisms in OATP1B1, BCRP and NTCP on pravastatin population pharmacokinetics in healthy Chinese volunteers using a non-linear mixed-effect modelling (NONMEM) approach. A two-compartment model with a first-order absorption and elimination described plasma pravastatin concentrations well. 2. Genetic polymorphisms of rs4149056 (OATP1B1) and rs2306283 (OATP1B1) were found to be associated with a significant (p < 0.01) decrease in the apparent clearance from the central compartment (CL/F), while rs2296651 (NTCP) increased CL/F to a significant degree (p < 0.01). The combination of these three polymorphisms reduced the inter-individual variability of CL/F by 78.8%. 3. There was minimal effect of rs2231137 (BCRP) and rs2231142 (BCRP) on pravastatin pharmacokinetics (0.01 < p < 0.05), whereas rs11045819 (OATP1B1), rs1061018 (BCRP) and rs61745930 (NTCP) genotypes do not appear to be associated with pravastatin pharmacokinetics based on the population model (p > 0.05). 4. The current data suggest that the combination of rs4149056, rs2306283 and rs2296651 polymorphisms is an important determinant of pravastatin pharmacokinetics. PMID:26744986

  9. Report: pharmacokinetic and drug interaction studies of pefloxacin with paracetamol (NNAID) in healthy volunteers in Pakistan.

    PubMed

    Gauhar, Shahnaz; Ali, Syed Ayub; Naqvi, Syed Baqir; Shoaib, Muhammad Harris

    2014-03-01

    In the present study, the pharmacokinetic and drug interaction evaluation of two drugs pefloxacin and paracetamol was carried out by a single-dose, two-treatment and two-sequence crossover design. Total fifteen healthy volunteers participated out of which ten completed the study. All were male volunteers, aged 22.36 years (means), with a mean weight of 76.45±12.05 Kg. The washout period between treatments was 5 week. Initially the method utilized for quantitative analysis of the drug was developed which was further validated. The study involved plasma protein precipitation with ethyl acetate and detection was done at 275nm. The retention time for pefloxacin 18±1 min and paracetamol were approximately 6±1 min, respectively. The calibration curve for pefloxacin was linear in the concentration range of 0.125-12.0mg/ml with r(2)=0.9987 in plasma. Standard concentration solution was maintained on the same temperature as that of volunteer's samples to optimize the periods for the determination of drug concentration in the plasma samples. Blood samples were collected from volunteers at different time intervals. The pharmacokinetics and drug interaction studies were anticipated by plotting concentration versus time-profiles. The value of AUC0-∞ in control was 67.355±3.174μg.h/ml, in treatment 61.242±3.868μg.h/ml along with relative bioavailability =91.395±4.864. Under the control and treatment condition the mean maximum plasma concentrations were found to be 4.679±0.248 μg/ml and 4.6595±0.266 μg/ml respectively. The average T(max) for plasma concentrations was 1.819±0.1743hr and 1.605 ±0.1134hr respectively. The biological half-lives in the two phases of studies were found to be 7.953±0.33hr in control and 7.7257±0.355hr in treatment. No significant effect were observed on the bioavailability and pharmacokinetics of pefloxacin by the concomitant administration with paracetamol, however very minor effect were observed that might be related with inter

  10. Gastric Re-acidification with Betaine HCl in Healthy Volunteers with Rabeprazole-Induced Hypochlorhydria

    PubMed Central

    Yago, Marc Anthony R.; Frymoyer, Adam R.; Smelick, Gillian S.; Frassetto, Lynda A.; Budha, Nageshwar R.; Dresser, Mark J.; Ware, Joseph A.; Benet, Leslie Z.

    2013-01-01

    Previous studies have demonstrated that increased gastric pH from the use of acid-reducing agents, such as proton-pump inhibitors or H2-receptor antagonists, can significantly impact the absorption of weakly basic drugs that exhibit pH-dependent solubility. Clinically practical strategies to mitigate this interaction have not been developed. This pilot study evaluated the extent and time course of gastric re-acidification after a solid oral dosage form of anhydrous betaine HCl in healthy volunteers with pharmacologically-induced hypochlorhydria. Six healthy volunteers with baseline normochlorhydria (fasting gastric pH < 4) were enrolled in this single period study. Hypochlorhydria was induced via 20 mg oral rabeprazole twice daily for four days. On the fifth day, an additional 20 mg dose of oral rabeprazole was given and gastric pH was monitored continuously using the Heidelberg pH capsule. After gastric pH > 4 was confirmed for 15 minutes, 1500 mg of betaine HCl was given orally with 90 mL of water and gastric pH was continuously monitored for 2 hours. Betaine HCl significantly lowered gastric pH by 4.5 (±0.5) units from 5.2 (±0.5) to 0.6 (±0.2) (P <0.001) during the 30 minute interval after administration. The onset of effect of betaine HCl was rapid, with a mean time to pH < 3 of 6.3 (±4.3) minutes. The re-acidification period was temporary with a gastric pH < 3 and < 4 lasting 73 (±33) and 77 (±30) minutes, respectively. Betaine HCl was well tolerated by all subjects. In healthy volunteers with pharmacologically-induced hypochlorhydria, betaine HCl was effective at temporarily lowering gastric pH. The rapid onset and relatively short duration of gastric pH reduction gives betaine HCl the potential to aid the absorption of orally administered weakly basic drugs that exhibit pH-dependent solubility when administered under hypochlorhydric conditions. PMID:23980906

  11. Quantification of serotonin O-sulphate by LC-MS method in plasma of healthy volunteers

    PubMed Central

    Lozda, Raimonds; Purviņš, Indulis

    2014-01-01

    The objective of this study was to test the hypothesis that serotonin O-sulphate (5-HT-SO4) could be quantified in human plasma using modern liquid chromatography–mass spectrometry (LC-MS) method as well as develop and validate that method. First, a suitable LC-MS method for detection of 5-HT-SO4 in human plasma samples was developed and validated. Second, a Pilot phase involving four healthy volunteers was executed, where a basal plasma level of 5-HT-SO4 was measured for all subjects and for one after the intake of 100 mg of a 5-hydroxytryptophan (5-HTP) -containing food supplement used to promote serotonergic stimulation of the central nervous system. The basal level of 0.9–2.8 ng/mL of 5-HT-SO4 was observed. The changes of plasma 5HT-O-SO4 showed 1.2 ng/mL before and 22.6 ng/mL 1 h after stimulation. Finally, nine healthy volunteers were selected for the Study phase, where a basal plasma level of 5-HT-SO4 was measured before and after the intake of 5-HTP. One hour after stimulation, six study subjects showed a decrease in 5-HT-SO4 levels while three subjects showed an increase. The changes of plasma 5HT-O-SO4 from the Study phase showed an average 5-HT-SO4 level of 19.2 ng/mL before and 15.7 ng/mL 1 h after stimulation indicating ability of method to emphasize quantitative changes. This was the first study in which naturally occurring 5-HT-SO4 was detected in the samples of human plasma obtained from healthy volunteers. The method developed herein is specific to the measurement of 5-HT-SO4, sensitive enough to quantify intra-individual changes in the samples of plasma and opens up new possibilities to evaluate pathways of serotonin metabolism by minimally invasive methods. The discovery of novel biomarkers using such approaches is increasingly required to expedite development of mechanism-based therapeutics and patient stratification. PMID:24782770

  12. UGT1A6 genotype-related pharmacokinetics of deferiprone (L1) in healthy volunteers

    PubMed Central

    Limenta, Lie Michael George; Jirasomprasert, Totsapol; Tankanitlert, Jeeranut; Svasti, Saovaros; Wilairat, Prapin; Chantharaksri, Udom; Fucharoen, Suthat; Morales, Noppawan Phumala

    2008-01-01

    AIMS To examine the effects of UGT1A6 polymorphisms on the pharmacokinetics of deferiprone in healthy volunteers. METHODS Twenty-two healthy volunteers were enrolled and grouped according to UGT1A6 genotype. After an overnight fast, the subjects received a single oral dose of 25 mg kg−1 deferiprone. Blood samples were collected at 0, 15, 30, 45, 60, 90, 120, 180, 240, 300 and 360 min after dosing. Urine output was collected at 0, 0–2, 2–4, 4–8, 8–12 and 12–24 h. Deferiprone (L1) and deferiprone-glucuronide (L1G) concentrations in serum and urine were determined using a validated high-performance liquid chromatography method. UGT1A6 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS No statistically significant differences in any pharmacokinetic parameters of either deferiprone or deferiprone-glucuronide among the genotype groups were noted. Likewise, there were no statistically significant differences in 24-h urinary deferiprone and deferiprone-glucuronide excretion among the genotype groups. Significant differences between men and women were found in AUC0–∞, Vd/F, and CL/F of deferiprone. Gender differences in 24-h urinary deferiprone and its metabolite excretion, however, failed to reach statistical significance. The Vd/F of deferiprone was found to correlate significantly with serum ferritin (rs = 0.665; P = 0.001). CONCLUSION The studied single nucleotide polymorphisms in UGT1A6 do not appear to exert statistically significant effects on the single-dose pharmacokinetics of deferiprone. Gender appears to influence the serum pharmacokinetics of deferiprone, but not urinary excretion of deferiprone and its metabolite. Body iron stores may have an influence on the extent of extravascular deferiprone distribution. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT UGT1A6 has been proposed as the predominant isoform responsible for the glucuronidation of deferiprone. UGT1A6*2 allele has been

  13. Relative Bioavailability of Fentanyl Following Various Dosing Regimens of Fentanyl Buccal Tablet in Healthy Japanese Volunteers

    PubMed Central

    Darwish, Mona; Tempero, Kenneth; Jiang, John G; Simonson, Philip G

    2008-01-01

    Background Fentanyl buccal tablet (FBT; FENTORA®, Cephalon, Inc., Frazer, PA, USA) is indicated in the US for breakthrough pain in patients with cancer who are already receiving and are tolerant to around-the-clock opioid therapy for underlying persistent cancer pain. For each individual patient, FBT should be titrated to the effective dose. Objective The primary objective was to characterize the pharmacokinetic parameters of FBT 400 µg administered as a single 400 µg tablet (regimen A) or as two 200 µg tablets given simultaneously (regimen B) and determine whether these are bioequivalent in healthy Japanese volunteers. Regimen C (two 200 µg tablets 30 minutes apart) was also compared as a secondary objective. Methods Healthy Japanese adults received regimens A, B, and C in a crossover fashion. Naltrexone was given to minimize the opioid effects of fentanyl. Serum fentanyl concentrations were determined in venous blood collected through 36 hours post dose. Regimens were declared bioequivalent with respect to bioavailability (as reflected by AUC0–∞, AUC0–last, and Cmax) if the 90% confidence interval (CI) of the regimens' ratio fell within 0.80–1.25 (80%–125%). Results Twenty-nine volunteers (13 men, 16 women) were enrolled; 24 completed the study. Regimens A and B had bioequivalent systemic exposure parameters (B/A [90% CI]: AUC0–∞108.4 [103.4, 113.7], AUC0–last 106.1 [100.7, 111.7], and Cmax 92.3 [83.2, 102.4]). Regimen C was bioequivalent to both A and B for AUCs, but only to B for Cmax. Median time to Cmax was 45 minutes for regimen A and 60 minutes for regimens B and C. The most frequent AEs were dizziness, application-site erythema, headache, somnolence, nausea, and vomiting. All AEs were mild or moderate. Conclusions Bioavailability of fentanyl after FBT 400 µg administered as a single tablet was bioequivalent to that after 2 simultaneously administered 200 µg tablets in healthy Japanese volunteers. AEs were mild or moderate. PMID

  14. 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

  15. Impact of Surotomycin on the Gut Microbiota of Healthy Volunteers in a Phase 1 Clinical Trial.

    PubMed

    Citron, Diane M; Tyrrell, Kerin L; Dale, Suzanne E; Chesnel, Laurent; Goldstein, Ellie J C

    2016-04-01

    Clostridium difficile-associated diarrhea has been associated with disruption of the normal intestinal microbiota, particularly theBacteroides fragilisgroup andPrevotellaspecies. Surotomycin is a bactericidal cyclic lipopeptide in development for treatment ofClostridium difficile-associated diarrhea that has selective and potent activity againstC. difficileand other Gram-positive bacteria and a minimal impact on intestinal Gram-negative organisms. The impacts of ascending doses of surotomycin on major organism groups in the gut microbiota of healthy volunteers were evaluated during a randomized, double-blind, placebo-controlled, multiple-dose phase 1 study. Thirty volunteers were randomized into 3 cohorts, using a 4:1 ratio, to receive 250 mg, 500 mg, or 1,000 mg of surotomycin, or placebo, twice daily for 14 days. Stool samples collected at baseline (days 0 and 1) and at the end of treatment (days 13 to 15) were cultured quantitatively. TheB. fragilisgroup, theBacteroides/Prevotellagroup, andEnterobacteriaceaewere also quantified by quantitative real-time PCR. Baseline and end-of-treatment stool samples showed 1- to 2-log10CFU/g reductions in total bacterial counts for most volunteers. Various decreases in clostridial,Lactobacillus-Bifidobacteriumgroup, and enterococcus-streptococcus group counts occurred while patients were receiving surotomycin, whereas the enterobacteria and theB. fragilisgroup persisted at the end of treatment. There was no change in enterococcus MICs of surotomycin, nor was vancomycin-resistantEnterococcusdetected after exposure. Surotomycin at doses of up to 1,000 mg twice daily had only modest disruptive effects on the gut microbiota. The potential sparing of the gut microbiota by surotomycin may decrease the risk of disease recurrence. PMID:26787687

  16. Effect of the CYP3A inhibitors, diltiazem and ketoconazole, on ticagrelor pharmacokinetics in healthy volunteers

    PubMed Central

    Teng, Renli; Butler, Kathleen

    2013-01-01

    Objectives Two open-label, two-period, crossover studies in healthy volunteers were designed to determine the pharmacokinetic interactions between ticagrelor, a P2Y12 receptor antagonist, and a moderate (diltiazem) and a strong (ketoconazole) cytochrome P450 (CYP) 3A inhibitor. Methods Seventeen volunteers received diltiazem (240 mg once daily) for 14 days. In the second study, ketoconazole (n = 14) 200 mg twice daily was given for 10 days. A single oral 90-mg ticagrelor dose was administered on day 8 (diltiazem) or day 4 (ketoconazole). In each study, volunteers received a single 90-mg oral dose of ticagrelor before or after washout (≥14 days). Pharmacokinetic parameters for ticagrelor, AR-C124910XX (primary metabolite), diltiazem, and ketoconazole were assessed. Results Compared with ticagrelor alone, diltiazem co-administration significantly increased the mean maximum concentration (Cmax) and mean area under the plasma concentration–time curve (AUC) for ticagrelor by 69% and 174%, respectively. Diltiazem co-administration reduced Cmax by 38% but had no significant effect on AUC for AR-C124910XX. Cmax and AUC for ticagrelor were increased by 135% and 632%, respectively, by ketoconazole co-administration, whereas these parameters were reduced by 89% and 56%, respectively, for AR-C124910XX. Diltiazem and ketoconazole pharmacokinetic parameters were not significantly affected by the presence of ticagrelor. Conclusions These results suggest that ticagrelor can be co-administered with moderate CYP3A inhibitors. However, co-administration of strong CYP3A inhibitors with ticagrelor is not recommended.

  17. Cognitive effects of intramuscular ketamine and oral triazolam in healthy volunteers

    PubMed Central

    Carter, Lawrence P.; Kleykamp, Bethea A.; Griffiths, Roland R.

    2012-01-01

    Rationale Several studies have documented impairments in memory processes as a result of ketamine administration; however, few studies have compared the profile of cognitive effects of ketamine to other drugs. Objectives The aim of this study was to compare the cognitive effects of ketamine with those of triazolam in healthy volunteers. Methods Doses of ketamine (0.2, 0.4 mg/kg intramuscular (i.m.)), triazolam (0.2, 0.4 mg/70 kg p.o.), and double-dummy placebos were administered to 20 volunteers under repeated measures, counterbalanced, double-blind conditions. Peak physiological, psychomotor, subjective, and cognitive effects were examined. Results Ketamine impaired balance when balance was assessed early in the task order, whereas triazolam impaired psychomotor coordination and divided attention irrespective of task order. Triazolam also tended to produce greater effects on working memory and episodic memory tasks than ketamine at doses that produced lower subjective effects and higher estimates of performance. Conclusions Ketamine produces less cognitive impairment than triazolam at doses that produced greater subjective effects. Thus ketamine does not produce the underestimation of cognitive impairment typically seen with triazolam. PMID:23096769

  18. 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

  19. 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

  20. 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. PMID:26924285

  1. [Pharmacokinetics of cefixime in healthy volunteers after a single oral administration of 200 mg].

    PubMed

    Montay, G; Le Liboux, A; Thebault, J J; Roche, G; Frydman, A; Gaillot, J

    1989-10-11

    The antibacterial activity of cefixime is identical with that of parenteral third generation cephalosporins. Its kinetics were studied in 24 healthy male volunteers who received one single 200 mg tablet. Cmax was 3.25 mg/l and Tmax was 4 h. After 12 hours, serum concentrations were still as high as 0.70 mg/l. Half-life was 3.3 h and urinary excretion was not predominant. Thus, cefixime was characterized by its relatively long serum half-life as compared with other cephalosporins. Despite some degree of individual variations, serum and urine concentrations of the antibiotic remained for 12 hours above the MIC of susceptible pathogens. PMID:2530537

  2. Bioequivalence study of 2 orodispersible formulations of ondansetron 8 mg in healthy volunteers.

    PubMed

    Cánovas, M; Rios, J; Domenech, G; Cebrecos, J; Pelagio, P; Canals, M; Polonio, F; Cabré, F

    2012-02-01

    This study was designed to compare the rate and extent of absorption of 2 oral formulations of ondansetron (CAS 99614-02-5) 8 mg orodispersible tablets in healthy volunteers. 22 subjects were administered ondansetron orodispersible tablets of test and reference formulation in a single-dose, 2-period, 2-sequence, fasting, open-label, crossover and randomised study. Plasma concentrations were determined by LC/MS/MS. Log-transformed AUCs and Cmax values were tested for bioequivalence based on the ratios of the geometric means (test/reference). Tmax 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 [1] it may be therefore concluded that test formulation of ondansetron 8 mg orodispersible tablet is bioequivalent to the reference formulation. PMID:22344549

  3. Bioequivalence of oral and intravenous ofloxacin after multiple-dose administration to healthy male volunteers.

    PubMed Central

    Flor, S C; Rogge, M C; Chow, A T

    1993-01-01

    The bioequivalence of oral and intravenous ofloxacin was investigated after the administration of multiple doses of 400 mg every 12 h to 20 healthy male volunteers in a randomized, crossover, open-label study. Ofloxacin concentrations in plasma were evaluated after 4 days of oral or intravenous (1-h infusion) dosing with a 3-day wash-out period between regimens. As expected, delivery to the systemic circulation took slightly longer after the oral dosing (time to maximum concentration of drug in serum of 1.7 h) relative to the 1-h intravenous infusion, but the systemic availabilities of ofloxacin by the two routes of administration were equivalent (area under the concentration-time curve from 0 to 12 h ratio of 95%). Since previous studies have not demonstrated any change in the bioavailability of ofloxacin in infectious disease patients, this study supports the interchangeability of these dosing regimens. PMID:8363378

  4. Characterization of renal biomarkers for use in clinical trials: biomarker evaluation in healthy volunteers

    PubMed Central

    Brott, David A; Adler, Scott H; Arani, Ramin; Lovick, Susan C; Pinches, Mark; Furlong, Stephen T

    2014-01-01

    Background Several preclinical urinary biomarkers have been qualified and accepted by the health authorities (US Food and Drug Administration, European Medicines Agency, and Pharmaceuticals and Medical Devices Agency) for detecting drug-induced kidney injury during preclinical toxicologic testing. Validated human assays for many of these biomarkers have become commercially available, and this study was designed to characterize some of the novel clinical renal biomarkers. The objective of this study was to evaluate clinical renal biomarkers in a typical Phase I healthy volunteer population to determine confidence intervals (pilot reference intervals), intersubject and intrasubject variability, effects of food intake, effect of sex, and vendor assay comparisons. Methods Spot urine samples from 20 male and 19 female healthy volunteers collected on multiple days were analyzed using single analyte and multiplex assays. The following analytes were measured: α-1-microglobulin, β-2-microglobulin, calbindin, clusterin, connective tissue growth factor, creatinine, cystatin C, glutathione S-transferase-α, kidney injury marker-1, microalbumin, N-acetyl-β-(D) glucosaminidase, neutrophil gelatinase-associated lipocalin, osteopontin, Tamm-Horsfall urinary glycoprotein, tissue inhibitor of metalloproteinase 1, trefoil factor 3, and vascular endothelial growth factor. Results Confidence intervals were determined from the single analyte and multiplex assays. Intersubject and intrasubject variability ranged from 38% to 299% and from 29% to 82% for biomarker concentration, and from 24% to 331% and from 10% to 67% for biomarker concentration normalized to creatinine, respectively. There was no major effect of food intake or sex. Single analyte and multiplex assays correlated with r2≥0.700 for five of six biomarkers when evaluating biomarker concentration, but for only two biomarkers when evaluating concentration normalized to creatinine. Conclusion Confidence intervals as well as

  5. Acute effects of the ampakine farampator on memory and information processing in healthy elderly volunteers.

    PubMed

    Wezenberg, Elke; Verkes, Robert Jan; Ruigt, Ge S F; Hulstijn, Wouter; Sabbe, Bernard G C

    2007-06-01

    Ampakines act as positive allosteric modulators of AMPA-type glutamate receptors and facilitate hippocampal long-term potentiation (LTP), a mechanism associated with memory storage and consolidation. The present study investigated the acute effects of farampator, 1-(benzofurazan-5-ylcarbonyl) piperidine, on memory and information processes in healthy elderly volunteers. A double-blind, placebo-controlled, randomized, cross-over study was performed in 16 healthy, elderly volunteers (eight male, eight female; mean age 66.1, SD 4.5 years). All subjects received farampator (500 mg) and placebo. Testing took place 1 h after drug intake, which was around Tmax for farampator. Subjects performed tasks assessing episodic memory (wordlist learning and picture memory), working and short-term memory (N-back, symbol recall) and motor learning (maze task, pursuit rotor). Information processing was assessed with a tangled lines task, the symbol digit substitution test (SDST) and the continuous trail making test (CTMT). Farampator (500 mg) unequivocally improved short-term memory but appeared to impair episodic memory. Furthermore, it tended to decrease the number of switching errors in the CTMT. Drug-induced side effects (SEs) included headache, somnolence and nausea. Subjects with SEs had significantly higher plasma levels of farampator than subjects without SEs. Additional analyses revealed that in the farampator condition the group without SEs showed a significantly superior memory performance relative to the group with SEs. The positive results on short-term memory and the favorable trends in the trail making test (CTMT) are interesting in view of the development of ampakines in the treatment of Alzheimer's disease and schizophrenia. PMID:17119538

  6. 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

  7. 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

  8. 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

  9. 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

  10. Pharmacokinetics of artemether and dihydroartemisinin in healthy Pakistani male volunteers treated with artemether-lumefantrine

    PubMed Central

    2010-01-01

    Background Artemether-lumefantrine is one of the most widely used anti-malarial drug combinations in the world with excellent tolerability and cure rates in adult and paediatric patients with uncomplicated falciparum malaria. The aim of this study was to evaluate the pharmacokinetics of artemether and its active metabolite, dihydroartemisinin, in healthy Pakistani volunteers. Methods Twelve healthy male Pakistani subjects, aged 20 to 50, were recruited into the study. A fixed oral combination of artemether-lumefantrine (80-480 mg) was given as a single oral dose. Frequent blood samples were collected and artemether and dihydroartemisinin were quantified in human plasma using solid-phase extraction and liquid chromatography coupled with tandem mass spectrometry. Drug concentration-time data were evaluated with non-compartmental analysis. Results Observed maximum concentrations (mean ± SD) of artemether and dihydroartemisinin were 184 ± 100 ng/mL and 126 ± 46 ng/mL, respectively. These concentrations were reached at 1.56 ± 0.68 hr and 1.69 ± 0.59 hr, respectively, after drug intake. The terminal elimination half-life of artemether and dihydroartemisinin were 2.00 ± 0.71 hr and 1.80 ± 0.31 hr, respectively. Apparent volume of distribution and oral clearance for artemether were estimated to 666 ± 220 L and 257 ± 140 L/hr. The same parameters were estimated to 702 ± 220 L and 269 ± 57 L/hr for dihydroartemisinin. Conclusions The overall pharmacokinetic properties of artemether and dihydroartemisinin in healthy Pakistani subjects are comparable to healthy subjects and patients from other populations. PMID:20932349

  11. 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

  12. Altered heart-rate variability in asthmatic and healthy volunteers exposed to concentrated ambient coarse particles.

    PubMed

    Gong, Henry; Linn, William S; Terrell, Sheryl L; Clark, Kenneth W; Geller, Michael D; Anderson, Karen R; Cascio, Wayne E; Sioutas, Constantinos

    2004-06-01

    Twelve mildly asthmatic and four healthy adults were exposed to filtered air (FA) and concentrated ambient coarse particles (CCP) supplied to a whole-body exposure chamber via a coarse particle concentrator with 15 parallel virtual impactors. Exposures were conducted in a Los Angeles suburb with high levels of motor-vehicle pollution and lasted 2 h with intermittent exercise. Mean CCP concentration was 157 microg/m(3) (range: 56-218 microg/m(3)) measured by continuous monitoring with a tapered-element oscillating microbalance (TEOM). On average, 80% of mass was coarse (2.5-10 microm aerodynamic diameter) and the rest <2.5 microm. Relative to FA, CCP exposure did not significantly alter respiratory symptoms, spirometry, arterial oxygen saturation, or airway inflammation according to exhaled nitric oxide and total and differential cell counts of induced sputum. After CCP exposure, Holter electrocardiograms showed small (p <.05) increases in heart rate and decreases in heart-rate variability, which were larger in healthy than in asthmatic subjects. Cardiac ectopy did not increase. In conclusion, acute exposure to elevated concentrations of ambient coarse particles elicited no obvious pulmonary effects but appeared to alter the autonomic nervous system of the heart in adult volunteers. PMID:15204749

  13. Pharmacokinetics of Artesunate Alone and in Combination with Sulfadoxine/Pyrimethamine in Healthy Sudanese Volunteers

    PubMed Central

    Matar, Kamal M.; Awad, Abdelmoneim I.; Elamin, Sakina B.

    2014-01-01

    Artesunate (AS) in combination with sulfadoxine/pyrimethamine (SP) is the first-line therapy for management of uncomplicated Plasmodium falciparum malaria in Sudan. The objective of this study was to assess the potential impact of SP on the pharmacokinetics of AS and its active metabolite, dihydroartemisinin (DHA), in healthy adults. A single-dose, randomized, open-label, crossover study design with a washout period of three weeks was performed with 16 volunteers. After oral administration of AS alone or in combination with SP, Tmax values of AS and DHA were significantly prolonged in the combination group (P < 0.05). However, there was no significant effect on the other pharmacokinetic parameters (P > 0.05). The t1/2 values of AS and DHA were significantly higher in females than in males (P < 0.05). The present findings suggest that co-administration of SP with AS has no clinically relevant impact on the pharmacokinetics of AS or DHA in healthy persons. PMID:24615137

  14. Effects of olanzapine and ziprasidone on glucose tolerance in healthy volunteers.

    PubMed

    Sacher, Julia; Mossaheb, Nilufar; Spindelegger, Christoph; Klein, Nikolas; Geiss-Granadia, Thomas; Sauermann, Robert; Lackner, Edith; Joukhadar, Christian; Müller, Markus; Kasper, Siegfried

    2008-06-01

    Atypical antipsychotics have been linked to a higher risk for glucose intolerance, and consequentially the development of type 2 diabetes mellitus (DM2). We have therefore set out to investigate the acute effects of oral administration of olanzapine and ziprasidone on whole body insulin sensitivity in healthy subjects. Using the standardized hyperinsulinemic euglycemic clamp technique we compared whole body insulin sensitivity of 29 healthy male volunteers after oral intake of either olanzapine 10 mg/day (n = 14) or ziprasidone 80 mg/day (n = 15) for 10 days. A significant decrease (p<0.001) in whole body insulin sensitivity from 5.7 ml/h/kg ( = mean, SM = 0.4 ml/h/kg) at baseline to 4.7 ml/h/kg ( = mean, SM = 0.3 ml/h/kg) after oral intake of olanzapine (10 mg/day) for 10 days was observed. The ziprasidone (80 mg/day) group did not show any significant difference (5.2+/-0.3 ml/h/kg baseline vs 5.1+/-0.3 ml/h/kg) after 10 days of oral intake. Our main finding demonstrates that oral administration of olanzapine but not ziprasidone leads to a decrease in whole body insulin sensitivity in response to a hyperinsulinemic euglycemic challenge. Our finding is suggestive that not all atypical antipsychotics cause acute direct effects on glucose disposal and that accurate determination of side effect profile should be performed when choosing an atypical antipsychotic. PMID:17712347

  15. Abdominal wall muscle elasticity and abdomen local stiffness on healthy volunteers during various physiological activities.

    PubMed

    Tran, D; Podwojewski, F; Beillas, P; Ottenio, M; Voirin, D; Turquier, F; Mitton, D

    2016-07-01

    The performance of hernia treatment could benefit from more extensive knowledge of the mechanical behavior of the abdominal wall in a healthy state. To supply this knowledge, the antero-lateral abdominal wall was characterized in vivo on 11 healthy volunteers during 4 activities: rest, pullback loading, abdominal breathing and the "Valsalva maneuver". The elasticity of the abdominal muscles (rectus abdominis, obliquus externus, obliquus internus and transversus abdominis) was assessed using ultrasound shear wave elastography. In addition, the abdomen was subjected to a low external load at three locations: on the midline (linea alba), on the rectus abdominis region and on lateral muscles region in order to evaluate the local stiffness of the abdomen, at rest and during "Valsalva maneuver". The results showed that the "Valsalva maneuver" leads to a statistically significant increase of the muscle shear modulus compared to the other activities. This study also showed that the local stiffness of the abdomen was related to the activity. At rest, a significant difference has been observed between the anterior (0.5N/mm) and the lateral abdomen locations (1N/mm). Then, during the Valsalva maneuver, the local stiffness values were similar for all locations (ranging from 1.6 to 2.2N/mm). This work focuses on the in vivo characterization of the mechanical response of the human abdominal wall and abdomen during several activities. In the future, this protocol could be helpful for investigation on herniated patients. PMID:26994992

  16. 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. PMID:23813302

  17. Reversibility of Apixaban Anticoagulation with a Four-Factor Prothrombin Complex Concentrate in Healthy Volunteers.

    PubMed

    Nagalla, S; Thomson, L; Oppong, Y; Bachman, B; Chervoneva, I; Kraft, W K

    2016-06-01

    It was hypothesized that the four-factor prothrombin complex concentrate (4F-PCC) Kcentra 25 unit/kg would reverse impairment of thrombin generation in healthy volunteers dosed with apixaban to steady state. In this randomized, two-period crossover, assessor-blinded trial, 12 healthy subjects received 5 mg apixaban every 12 h. Three h after the fifth dose, four-factor prothrombin complex concentrate (4F-PCC) 25 unit/kg or saline were infused. Serial blood samples were assessed for thrombin generation using PPP-reagent and PPP-reagent low, anti-Xa, PT, and PTT assays. Geometric mean ratio was calculated at 30 min postinfusion, and at 24, 48, and 72 h. Peak thrombin generation was 76% higher at 30 min postinfusion with 4F-PCC (p = 0.025). The difference declined to 24% at 24 h and resolved by 48 h. Other thrombin generation parameters were also partially normalized. There was no difference between 4F-PCC and saline in anti-Xa assessment at 30 min or later time points. PMID:27170068

  18. Effects of oxcarbazepine and phenytoin on the EEG and cognition in healthy volunteers.

    PubMed

    Salinsky, M C; Spencer, D C; Oken, B S; Storzbach, D

    2004-12-01

    We studied the EEG and cognitive effects of oxcarbazepine (OXC) and phenytoin (PHT) using a double-blind, randomized, parallel-group design. Thirty-two healthy volunteers received a maximum of 1200 mg of OXC or 360 mg of PHT. EEG and cognitive testing were performed at baseline and after 12 weeks of treatment. For each subject and measure, test-retest Z scores were calculated from regression equations derived from 73 healthy controls. Twenty-six subjects completed the study. Both the OXC and PHT groups had significant slowing of the EEG peak frequency and increased relative theta and delta power. Differences between AEDs (antiepileptic drugs) were not significant. Significant cognitive effects were seen on 5 of 20 measures, primarily measures of motor speed and reaction time. Again, there were no significant differences between AEDs. The only significant difference between AEDs was for the POMS-Vigor scale, favoring OXC. The small sample size may have contributed to the lack of significant differences between AEDs. PMID:15582838

  19. Comparison of the effects of pantethine and fursultiamine on plasma gastrointestinal peptide levels in healthy volunteers.

    PubMed

    Suzuki, Yosuke; Itoh, Hiroki; Abe, Tomohide; Nishimura, Fumihiro; Sato, Yuhki; Takeyama, Masaharu

    2011-01-01

    Pantethine and fursultiamine have been evaluated for their clinical usefulness in the treatment and prevention of uncomplicated postoperative adhesive intestinal obstruction. In recent years, the actions of drugs used to treat gastrointestinal diseases have been elucidated pharmacologically from the viewpoints of gastrointestinal peptide levels. We examined the effects of pantethine and fursultiamine on plasma levels of calcitonin gene-related peptide (CGRP)-, vasoactive intestinal polypeptide (VIP)-, motilin- and substance P (SP)-like immunoreactive substances (IS) in healthy subjects. An open-labeled study was conducted on five healthy volunteers. Each subject was administered a single oral dose of pantethine, fursultiamine and placebo at intervals of one month. Venous blood samples were collected before and at 20, 40, 60, 90, 120, 180 and 240 min after each administration. Plasma peptide levels were measured using a highly sensitive enzyme immunoassay. A single oral dose of pantethine resulted in significant increases of plasma CGRP- and VIP-IS levels compared to placebo. Furthermore, areas under the plasma concentration-time curves (AUC(0-240)) of CGRP- and VIP-IS were significantly higher after pantethine administration compared with placebo. On the other hand, fursultiamine had no effect on plasma levels and AUC(0-240) of CGRP-, VIP-, motilin- and SP-IS. This study demonstrated the different effects of pantethine and fursultiamine from the viewpoint of plasma gastrointestinal peptide changes. The pharmacological effects of pantethine may be closely related to the changes in plasma CGRP- and VIP-IS levels. PMID:21963510

  20. Complete Blood Count Reference Intervals for Healthy Han Chinese Adults

    PubMed Central

    Mu, Runqing; Guo, Wei; Qiao, Rui; Chen, Wenxiang; Jiang, Hong; Ma, Yueyun; Shang, Hong

    2015-01-01

    Background Complete blood count (CBC) reference intervals are important to diagnose diseases, screen blood donors, and assess overall health. However, current reference intervals established by older instruments and technologies and those from American and European populations are not suitable for Chinese samples due to ethnic, dietary, and lifestyle differences. The aim of this multicenter collaborative study was to establish CBC reference intervals for healthy Han Chinese adults. Methods A total of 4,642 healthy individuals (2,136 males and 2,506 females) were recruited from six clinical centers in China (Shenyang, Beijing, Shanghai, Guangzhou, Chengdu, and Xi’an). Blood samples collected in K2EDTA anticoagulant tubes were analyzed. Analysis of variance was performed to determine differences in consensus intervals according to the use of data from the combined sample and selected samples. Results Median and mean platelet counts from the Chengdu center were significantly lower than those from other centers. Red blood cell count (RBC), hemoglobin (HGB), and hematocrit (HCT) values were higher in males than in females at all ages. Other CBC parameters showed no significant instrument-, region-, age-, or sex-dependent difference. Thalassemia carriers were found to affect the lower or upper limit of different RBC profiles. Conclusion We were able to establish consensus intervals for CBC parameters in healthy Han Chinese adults. RBC, HGB, and HCT intervals were established for each sex. The reference interval for platelets for the Chengdu center should be established independently. PMID:25769040

  1. 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

  2. Clinical pharmacology of DP-b99 in healthy volunteers: First administration to humans

    PubMed Central

    Rosenberg, Gilad; Angel, Itzchak; Kozak, Alex

    2005-01-01

    Aims To investigate the safety, tolerability and pharmacokinetics of DP-b99 in healthy volunteers. DP-b99 is a newly developed lipophilic, cell permeable derivative of BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid), which selectively modulates the distribution of metal ions in hydrophobic milieu, and is in clinical development as a neuroprotectant for cerebral ischaemic stroke. To our knowledge no BAPTA derivative has ever been administered to man. Here we report the first human administration of DP-b99 in a phase I, two-part, double-blind, randomized placebo controlled study, with single IV doses of 0.003–1.0 mg kg−1 day−1 DP-b99 (part 1) or multiple ascending doses of 0.03–1.0 mg kg−1 day−1 DP-b99 over 4 days (part 2). Methods A double-blind, dose escalating tolerability study of DP-b99 in normal (young – aged between 18 and 40 years and elderly – aged between 65 and 85 years) healthy adult male volunteers was conducted. Part 1 of the study investigated single administration of ascending intravenous doses, and part 2 examined the effects of ascending doses given repeatedly over 4 days. Twenty-four young volunteers in part 1 received single dose administrations and 26 young volunteers in part 2 received repeated ascending dose administrations of either intravenous DP-b99 or placebo. Subsequently, 10 elderly volunteers received repeated intravenous DP-b99 (1 mg kg−1) or placebo in part 2 over 4 days. Adverse events were identified by either subject self reporting or based upon laboratory parameters (blood chemistry, complete blood cell count, prothrombin time (PT), activated partial thromboplastin (PTT), physical examination, vital signs (blood pressure, pulse rate, respiratory rate, body temperature) and urinalysis. A comprehensive set of cardiovascular parameters was assessed as well (blood pressure, 12 lead-ECG recordings and continuous bedside cardiac monitoring for 6 h on day 1). Results The administration of DP-b99 up

  3. 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

  4. Short- and midterm repeatability of magnetic resonance elastography in healthy volunteers at 3.0 T.

    PubMed

    Shi, Yu; Guo, Qiyong; Xia, Fei; Sun, Jiaxing; Gao, Yuying

    2014-07-01

    The purpose of this study was to evaluate the short- and midterm repeatability of liver stiffness measurements with magnetic resonance elastography (MRE) in healthy subjects at 3.0T. Twenty-two healthy volunteers were enrolled in this prospective study. The stiffness measurements were obtained from three slices with three repeated acquisitions for each slice (session 1) by two independent raters. After a mean period of 7±2days (session 2) and 195±15days (session 3), each subject was scanned again using the same protocol and MR system. The liver stiffness differences were calculated between sessions or raters. The intraclass correlation coefficient (ICC) was calculated to assess interrater agreement and intersession agreement. The stiffness differences over the short- and midterm intervals was (-0.004±0.086) kPa for sessions 1-2, lower than (-0.055±0.150) kPa for sessions 1-3 and (-0.051±0.173) kPa for sessions 2-3. The liver stiffness was more repeatable for the short-term interval with the mean overall ICC of 0.96 (sessions 1-2) (95% confidence interval [CI]: 0.90-0.98) compared with 0.91 (sessions 1-3) (95% CI: 0.78-0.96) and 0.87 (sessions 2-3) (95% CI: 0.69-0.95) for the midterm intervals. The overall ICC of interrater agreement was excellent at 0.987 (95% CI: 0.983 to 0.990). These results confirm that MRE is a reproducible technique for liver stiffness quantification over short- and midterm intervals up to 6months in a healthy population at 3.0T. PMID:24650683

  5. Amphetamine sensitisation and memory in healthy human volunteers: a functional magnetic resonance imaging study.

    PubMed

    O'Daly, Owen G; Joyce, Daniel; Tracy, Derek K; Stephan, Klaas E; Murray, Robin M; Shergill, Sukhwinder

    2014-09-01

    Amphetamine sensitisation (AS) is an established animal model of the hypersensitivity to psychostimulants seen in patients with schizophrenia. AS also models the dysregulation of mesolimbic dopamine signalling which has been implicated in the development of psychotic symptoms. Recent data suggest that the enhanced excitability of mesolimbic dopamine neurons in AS is driven by a hyperactivity of hippocampal (subiculum) neurons, consistent with a strong association between hippocampal dysfunction and schizophrenia. While AS can be modelled in human volunteers, its functional consequences on dopaminoceptive brain regions (i.e. striatum and hippocampus) remains unclear. Here we describe the effects of a sensitising dosage pattern of dextroamphetamine on the neural correlates of motor sequence learning in healthy volunteers, within a randomised, double-blind, parallel-groups design. Behaviourally, sensitisation was characterised by enhanced subjective responses to amphetamine but did not change performance (i.e. learning rate) during an explicit sequence learning task. In contrast, functional magnetic resonance imaging (fMRI) measurements showed that repeated intermittent amphetamine exposure was associated with increased blood-oxygen-level dependent (BOLD) signal within the medial temporal lobe (MTL) (subiculum/entorhinal cortex) and midbrain, in the vicinity of the substantia nigra/ventral tegmental area (SN/VTA) during sequence encoding. Importantly, MTL hyperactivity correlated with the sensitisation of amphetamine-induced attentiveness. The MTL-midbrain hyperactivity reported here mirrors observations in sensitised rodents and is consistent with contemporary models of schizophrenia and behavioural sensitisation. These findings of meso-hippocampal hyperactivity during AS thus link pathophysiological concepts of dopamine dysregulation to cognitive models of psychosis. PMID:24671338

  6. 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).

  7. 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. PMID:26075963

  8. Absolute and Trend Accuracy of a New Regional Oximeter in Healthy Volunteers During Controlled Hypoxia

    PubMed Central

    Paidy, Samata; Kashif, Faisal

    2014-01-01

    BACKGROUND: Traditional patient monitoring may not detect cerebral tissue hypoxia, and typical interventions may not improve tissue oxygenation. Therefore, monitoring cerebral tissue oxygen status with regional oximetry is being increasingly used by anesthesiologists and perfusionists during surgery. In this study, we evaluated absolute and trend accuracy of a new regional oximetry technology in healthy volunteers. METHODS: A near-infrared spectroscopy sensor connected to a regional oximetry system (O3TM, Masimo, Irvine, CA) was placed on the subject’s forehead, to provide continuous measurement of regional oxygen saturation (rSo2). Reference blood samples were taken from the radial artery and internal jugular bulb vein, at baseline and after a series of increasingly hypoxic states induced by altering the inspired oxygen concentration while maintaining normocapnic arterial carbon dioxide pressure (Paco2). Absolute and trend accuracy of the regional oximetry system was determined by comparing rSo2 against reference cerebral oxygen saturation (Savo2), that is calculated by combining arterial and venous saturations of oxygen in the blood samples. RESULTS: Twenty-seven subjects were enrolled. Bias (test method mean error), standard deviation of error, standard error of the mean, and root mean square accuracy (ARMS) of rSo2 compared to Savo2 were 0.4%, 4.0%, 0.3%, and 4.0%, respectively. The limits of agreement were 8.4% (95% confidence interval, 7.6%–9.3%) to −7.6% (95% confidence interval, −8.4% to −6.7%). Trend accuracy analysis yielded a relative mean error of 0%, with a standard deviation of 2.1%, a standard error of 0.1%, and an ARMS of 2.1%. Multiple regression analysis showed that age and skin color did not affect the bias (all P > 0.1). CONCLUSIONS: Masimo O3 regional oximetry provided absolute root-mean-squared error of 4% and relative root-mean-squared error of 2.1% in healthy volunteers undergoing controlled hypoxia. PMID:25405692

  9. Pharmacokinetic interactions between ritonavir and quinine in healthy volunteers following concurrent administration

    PubMed Central

    Soyinka, Julius O; Onyeji, Cyprian O; Omoruyi, Sharon I; Owolabi, Adegbenga R; Sarma, Pullela V; Cook, James M

    2010-01-01

    AIMS To evaluate the pharmacokinetic interactions between ritonavir and quinine in healthy volunteers. METHODS Ten healthy volunteers were each given 600-mg single oral doses of quinine alone, ritonavir alone (200 mg every 12 h for 9 days), and quinine in combination with ritonavir, in a three-period pharmacokinetic nonrandomized sequential design study. Quinine was co-administered with the 15th dose of ritonavir. Blood samples collected at predetermined time intervals were analysed for ritonavir, quinine and its major metabolite, 3-hydroxyquinine, using a validated high-performance liquid chromatography method. RESULTS Concurrent ritonavir administration resulted in about fourfold increases in both the Cmax and AUCT[Cmax 2.79 ± 0.22 vs. 10.72 ± 0.32 mg l−1, 95% confidence interval (CI) 7.81, 8.04; AUC 50.06 ± 2.52 vs. 220.47 ± 6.68 mg h−1 l−1, 95% CI 166.3, 175.3], a significant increase (P < 0.01) in the elimination half-life (11.15 ± 0.80 vs. 13.37 ± 0.33 h, 95% CI 1.64, 2.77) and about a 4.5-fold decrease in CL/F (12.01 ± 0.61 vs. 2.71 ± 0.09 l h−1) of quinine. Also, with ritonavir, there was a pronounced reduction of AUC(metabolite)/AUC(unchanged drug) ratio of quinine (1.35 ± 0.10 vs. 0.13 ± 0.02) along with a marked decrease in Cmax (1.80 ± 0.12 vs. 0.96 ± 0.09 mg l−1) and AUC0–48h (62.80 ± 6.30 vs. 25.61 ± 2.44 mg h−1 l−1) of the metabolite. Similarly, quinine caused modest but significant increases (P < 0.01) in the Cmax, AUC and elimination T½ of ritonavir. CONCLUSIONS Downward dosage adjustment of quinine appears necessary when concurrently administered with ritonavir. PMID:20233197

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

    PubMed Central

    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

    2013-01-01

    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. PMID:24223659

  11. Central nervous system effects of haloperidol on THC in healthy male volunteers.

    PubMed

    Liem-Moolenaar, Marieke; te Beek, Erik T; de Kam, Marieke L; Franson, Kari L; Kahn, René S; Hijman, Ron; Touw, Daan; van Gerven, Joop M A

    2010-11-01

    In this study, the hypothesis that haloperidol would lead to an amelioration of Δ9-tetrahydrocannabinol (THC)-induced 'psychotomimetic' effects was investigated. In a double-blind, placebo-controlled, partial three-way crossover ascending dose study the effects of THC, haloperidol and their combination were investigated in 35 healthy, male mild cannabis users, measuring Positive and Negative Syndrome Scale, Visual Analogue Scales for alertness, mood, calmness and psychedelic effects, saccadic and smooth pursuit eye measurements, electroencephalography, Body Sway, Stroop test, Visual and Verbal Learning Task, hormone levels and pharmacokinetics. Compared with placebo, THC significantly decreased smooth pursuit, Visual Analogue Scales alertness, Stroop test performance, immediate and delayed word recall and prolactin concentrations, and significantly increased positive and general Positive and Negative Syndrome Scale score, Visual Analogue Scales feeling high, Body Sway and electroencephalography alpha. Haloperidol reversed the THC-induced positive Positive and Negative Syndrome Scale increase to levels observed with haloperidol alone, but not THC-induced 'high' feelings. Compared with placebo, haloperidol significantly decreased saccadic peak velocity, smooth pursuit, Visual Analogue Scales mood and immediate and delayed word recall and significantly increased Body Sway, electroencephalography theta and prolactin levels. THC-induced increases in positive Positive and Negative Syndrome Scale but not in Visual Analogue Scales feeling high were reversed by haloperidol. This indicates that psychotic-like effects induced by THC are mediated by dopaminergic systems, but that other systems are involved in 'feeling high'. Additionally, the clear reductions of psychotic-like symptoms by a clinically relevant dose of haloperidol suggest that THC administration may be a useful pharmacological cannabinoid model for psychotic effects in healthy volunteers. PMID:20142302

  12. 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

  13. Pharmacokinetics and clinical effects of multidose sublingual triazolam in healthy volunteers.

    PubMed

    Jackson, Douglass L; Milgrom, Peter; Heacox, Gail A; Kharasch, Evan D

    2006-02-01

    Triazolam is increasing in popularity as a premedication prescribed by dentists to help their fearful and anxious patients tolerate the potentially aversive nature of some dental procedures. Recent anecdotal reports suggest that incremental sublingual dosing of triazolam may be an effective technique for producing conscious sedation in the dental setting. Although promising, no laboratory or clinical data have been available to evaluate the efficacy or safety of this approach. This study was designed to determine the pharmacokinetics and sedative effects of incremental sublingual dosing of triazolam (total, 1.0 mg) in healthy adults. Ten healthy adult volunteers received sublingual triazolam (0.25 mg) followed by additional doses after 60 (0.50 mg) and 90 (0.25 mg) minutes. Plasma triazolam concentrations, clinical effects (Observer's Assessment of Alertness/Sedation score), and processed electroencephalogram (bispectral index score) were measured intermittently for 3 hours. Plasma triazolam concentrations (mean +/- SD, 5.1 +/- 1.1 ng/mL) and drug effects (Observer's Assessment of Alertness/Sedation score, 2 +/- 1; and the bispectral index score, 62 +/- 16) were greatest in all subjects at the end of the 3-hour evaluation period. Eight of the subjects had Observer's Assessment of Alertness/Sedation scores consistent with the definition of deep sedation or general anesthesia (Observer's Assessment of Alertness/Sedation score, <3) at some of the later time points in the 180 minutes of data collection. In comparison, 4 of the subjects had bispectral index scores less than 60 during these later time points of data collection. Given the considerable intersubject variability in triazolam concentrations and effects, additional research is needed to assess this multidosing strategy before it can be endorsed as a useful and safe sedation technique for managing fearful and anxious patients in dental practice. PMID:16415697

  14. The effects of ketamine and risperidone on eye movement control in healthy volunteers

    PubMed Central

    Schmechtig, A; Lees, J; Perkins, A; Altavilla, A; Craig, K J; Dawson, G R; William Deakin, J F; Dourish, C T; Evans, L H; Koychev, I; Weaver, K; Smallman, R; Walters, J; Wilkinson, L S; Morris, R; Williams, S C R; Ettinger, U

    2013-01-01

    The non-competitive N-methyl-D-aspartate receptor antagonist ketamine leads to transient psychosis-like symptoms and impairments in oculomotor performance in healthy volunteers. This study examined whether the adverse effects of ketamine on oculomotor performance can be reversed by the atypical antipsychotic risperidone. In this randomized double-blind, placebo-controlled study, 72 healthy participants performed smooth pursuit eye movements (SPEM), prosaccades (PS) and antisaccades (AS) while being randomly assigned to one of four drug groups (intravenous 100 ng ml−1 ketamine, 2 mg oral risperidone, 100 ng ml−1 ketamine plus 2 mg oral risperidone, placebo). Drug administration did not lead to harmful adverse events. Ketamine increased saccadic frequency and decreased velocity gain of SPEM (all P<0.01) but had no significant effects on PS or AS (all P⩾0.07). An effect of risperidone was observed for amplitude gain and peak velocity of PS and AS, indicating hypometric gain and slower velocities compared with placebo (both P⩽0.04). No ketamine by risperidone interactions were found (all P⩾0.26). The results confirm that the administration of ketamine produces oculomotor performance deficits similar in part to those seen in schizophrenia. The atypical antipsychotic risperidone did not reverse ketamine-induced deteriorations. These findings do not support the cognitive enhancing potential of risperidone on oculomotor biomarkers in this model system of schizophrenia and point towards the importance of developing alternative performance-enhancing compounds to optimise pharmacological treatment of schizophrenia. PMID:24326395

  15. 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

  16. Rifampin enhances cytochrome P450 (CYP) 2B6-mediated efavirenz 8-hydroxylation in healthy volunteers

    PubMed Central

    Cho, Doo-Yeoun; Shen, Joan H.Q.; Lemler, Suzanne M.; Skaar, Todd C; Li, Lang; Blievernicht, Julia; Zanger, Ulrich M.; Kim, Kwon-Bok; Shin, Jae-Gook; Flockhart, David A.; Desta, Zeruesenay

    2016-01-01

    The effect of rifampin on the in vivo metabolism of the antiretroviral drug efavirenz was evaluated in healthy volunteers. In a cross-over placebo control trial, healthy subjects (n = 20) were administered a single 600 mg oral dose of efavirenz after pretreatment with placebo or rifampin (600 mg/day for 10 days). Plasma and urine concentrations of efavirenz, 8-hydroxyefavirenz and 8,14-dihydroxyefavirenz were measured by LC–MS/MS. Compared to placebo treatment, rifampin increased the oral clearance (by ~2.5-fold) and decreased maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC0–∞) of efavirenz (by ~1.6- and ~2.5-fold respectively) (p < 0.001). Rifampin treatment substantially increased the Cmax and AUC0–12h of 8-hydroxyefavirenz and 8,14-dihydroxyefavirenz, metabolic ratio (AUC0–72h of metabolites to AUC0–72h efavirenz) and the amount of metabolites excreted in urine (Ae0–12hr) (all, p < 0.01). Female subjects had longer elimination half-life (1.6–2.2-fold) and larger weight-adjusted distribution volume (1.6– 1.9-fold) of efavirenz than male subjects (p < 0.05) in placebo and rifampin treated groups respectively. In conclusion, rifampin enhances CYP2B6-mediated efavirenz 8-hydroxylation in vivo. The metabolism of a single oral dose of efavirenz may be a suitable in vivo marker of CYP2B6 activity to evaluate induction drug interactions involving this enzyme. PMID:27053325

  17. Effect of food on the pharmacokinetics of rifalazil, a novel antibacterial, in healthy male volunteers.

    PubMed

    Chen, Y-X; Cabana, B; Kivel, N; Michaelis, A

    2007-07-01

    Rifalazil is a new antibiotic structurally related to rifampin but devoid of the metabolic liabilities typically associated with the rifamycin class of antibiotics. A randomized, 3-way crossover study in healthy male volunteers (n = 12) investigated the safety and pharmacokinetics of a single 25-mg oral rifalazil dose administered under a standard breakfast containing fat as 30% of calories, a high-fat breakfast containing fat as 60% of calories, and an overnight fast of 10 hours with a 21- to 28-day washout between doses. Systemic exposure to rifalazil based on Cmax, AUC(0-Tlast), and AUC(0-infinity) was increased progressively as the fat content of the test breakfast was increased from 30% to 60% compared with fasting. The confidence intervals for both fat-containing breakfasts are outside the limits of 80% to 125% allowed for food effect bioequivalence based on Cmax, AUC(0-Tlast), and AUC(0-infinity). This food effect may be a result of increased fractional absorption with increasing dietary fat content. Another striking finding was the large reduction of the pharmacokinetic intersubject variability after rifalazil administration with food. Rifalazil was safe and well tolerated under fed and fasted conditions. PMID:17463218

  18. Bioequivalence study of 8 mg ondansetron film-coated tablets in healthy Caucasian volunteers.

    PubMed

    Rudzki, P J; Kaza, M; Leś, A; Gilant, E; Ksycińska, H; Serafin-Byczak, K; Troć, M; Raszek, J; Piątkowska-Chabuda, E; Skowrońska-Smolak, M; Tarasiuk, A; Wilkowska, E; Łazowski, T

    2014-04-01

    The aim of the study was to investigate the bioequivalence of a generic product of 8 mg film-coated tablets (test) to the branded product (reference) at the same strength in order to apply for regulatory approval. The secondary objective of the study was to compare the tolerability of both products. A double blinded, randomized, cross-over, 2-period, comparative study was conducted in healthy Caucasian volunteers under fasting conditions. A single oral dose administration of the test or reference product was followed by a 7-day wash-out period. The ondansetron concentration was determined using a validated high performance liquid chromatography with a UV detection method. The 90% confidence interval of the point estimate (test over reference products) for C(max) and AUC(0-t) fell within the 80.00-125.00% acceptance range. The results of the study indicate that the film-coated tablets of Ondatron 8 mg manufactured by Tarchomińskie Zakłady Farmaceutyczne Polfa S.A. (test product) are bioequivalent to those of Zofran manufactured by GlaxoSmithKline Export Ltd (reference product). Both products were well tolerated. PMID:24132707

  19. Acute loading with proteins from different sources in healthy volunteers and diabetic patients.

    PubMed

    Nakamura, H; Yamazaki, M; Chiba, Y; Tani, N; Momotsu, T; Kamoi, K; Ito, S; Yamaji, T; Shibata, A

    1991-01-01

    To evaluate the effects of protein loading on glomerular filtration rate (GFR), urinary excretion rate of albumin (AER), and plasma concentration of amino acids, 10 healthy volunteers and six diabetics were studied before and after eating tuna fish, egg white, cheese, or tofu. Furthermore, to study the possible role of glucagon, growth hormone (GH), atrial natriuretic peptide (ANP), or kallikrein in the responses of GFR, these substances were measured before and after protein loading. GFR increased significantly (p less than .001) after ingestion of tuna fish. No significant differences were seen between the GFR before and that after ingestion of the other foods. AER was unchanged following protein loading. Plasma concentrations of alanine, glycine, and arginine increased to a greater degree after ingestion of tuna fish than after digestion of the other foods. This result suggests that the response of GFR after protein loading may differ from one protein to another, and that these responses may not be directly mediated by glucagon, GH, ANP, or kallikrein. PMID:1770024

  20. Pharmacokinetic and pharmacodynamic interaction of nadolol with itraconazole, rifampicin and grapefruit juice in healthy volunteers.

    PubMed

    Misaka, Shingen; Miyazaki, Nozomu; Yatabe, Midori S; Ono, Tomoyuki; Shikama, Yayoi; Fukushima, Tetsuhito; Kimura, Junko

    2013-07-01

    To evaluate effects of itraconazole, rifampicin and grapefruit juice on pharmacokinetics and pharmacodynamics of a hydrophilic non-selective β-adrenoceptor blocker nadolol, we conducted an open-label, four-way crossover study in 10 healthy male volunteers. A single oral dose of 30 mg nadolol was administered with water (control), itraconazole (100 mg), or grapefruit juice (300 mL), or after a 6-day pretreatment with rifampicin (450 mg/day). Plasma concentrations and urinary excretions of nadolol were measured over 48 hours after its dosing. Systolic and diastolic blood pressures and pulse rate were periodically recorded after nadolol administration as pharmacodynamic parameters. Itraconazole increased the peak plasma concentration and the area under the plasma concentration-time curve (AUC0-∞ ) of nadolol by 468% and 224% of control, respectively (P < .001). A slight, but not statistically significant, decrease in AUC0-∞ of nadolol was observed in rifampicin and grapefruit juice phases as compared to control. Elimination half-life for nadolol did not differ among the four phases. During itraconazole phase, nadolol reduced pharmacodynamic parameters to a greater extent than the other phases. These results suggest that itraconazole substantially increases the oral availability of nadolol possibly by the inhibition of intestinal P-glycoprotein, whereas grapefruit juice has little effect on nadolol pharmacokinetics. PMID:23677858

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

    PubMed

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

    2005-04-01

    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. PMID:15563628

  2. Effect of food or proton pump inhibitor treatment on the bioavailability of dacomitinib in healthy volunteers.

    PubMed

    Ruiz-Garcia, Ana; Masters, Joanna C; Mendes da Costa, Laure; LaBadie, Robert R; Liang, Yali; Ni, Grace; Ellery, Craig A; Boutros, Tanya; Goldberg, Zelanna; Bello, Carlo L

    2016-02-01

    This phase 1, open-label crossover study evaluated the relative bioavailability of dacomitinib in healthy volunteers under fed and fasted conditions and following coadministration with rabeprazole, a potent acid-reducing proton pump inhibitor (PPI). Twenty-four male subjects received a single dacomitinib 45-mg dose under 3 different conditions separated by washout periods of ≥ 16 days: coadministered with rabeprazole 40 mg under fasting conditions; alone under fasting conditions; and alone after a high-fat, high-calorie meal. Increased peak exposure of 23.7% (90% confidence interval [CI], 5.3%-45.2%) was detected with dacomitinib taken after food versus fasting. The adjusted geometric mean ratio (fed/fasted) for area under the plasma concentration-time curve from time zero to infinity (AUCinf ) was 114.2% (90%CI, 104.7%-124.5%) and not considered clinically meaningful. In the fasted state, a decrease in dacomitinib AUCinf was observed following rabeprazole versus dacomitinib alone (PPI+fasted/fasted alone): 71.1% (90%CI, 61.7%-81.8%). Dacomitinib was generally well tolerated. Dacomitinib may be taken with or without food. Use of long-acting acid-reducing agents, such as PPIs with dacomitinib should be avoided if possible. Shorter-acting agents such as antacids and H2-receptor antagonists may have lesser impact on dacomitinib exposure and may be preferable to PPIs if acid reduction is clinically required. PMID:26179237

  3. Pharmaceutical and pharmacokinetic characterization of a novel sublingual buprenorphine/naloxone tablet formulation in healthy volunteers

    PubMed Central

    Fischer, Andreas; Hjelmström, Peter

    2015-01-01

    Abstract Context Bitter taste, as well as dissolve time, presents a significant challenge for the acceptability of formulations for oral transmucosal drug delivery. Objective To characterize a novel sublingual tablet formulation of buprenorphine/naloxone with regards to pharmacokinetics, dissolve time and formulation acceptability. Methods Dry mixing techniques were employed to produce a small and fast dissolving buprenorphine/naloxone sublingual tablet formulation, OX219 (Zubsolv®), using sucralose and menthol as sweetener and flavor to mask the bitter taste of the active ingredients. Two cross-over studies were performed in healthy volunteers to evaluate pharmacokinetics, dissolve time and acceptability of OX219 5.7/1.4 mg tablets compared to the commercially available buprenorphine/naloxone formulations Suboxone® tablets and films (8/2 mg). Results Buprenorphine exposure was equivalent in OX219 and Suboxone tablets. Sublingual dissolve times were significantly shorter for OX219 than for Suboxone tablets and were similar to Suboxone films. The OX219 formulation received significantly higher subjective ratings for taste and overall acceptability than both Suboxone formulations. OX219 was preferred over Suboxone tablet and film formulations by 77.4% and 88.9% of subjects, respectively. Conclusions A sublingual tablet formulation with an improved acceptability has been successfully developed. PMID:24099551

  4. Uric acid quantification in fingernail of gout patients and healthy volunteers using HPLC-UV.

    PubMed

    Li, Xi-Ling; Shi, Qing; Jin, Wenlong; Li, Gao; Todoroki, Kenichiro; Mizuno, Hajime; Toyo'oka, Toshimasa; Min, Jun Zhe

    2016-08-01

    The presence of elevated uric acid (UA) levels is a sign of gout, that is, hyperuricemia. In this study the monitoring of the UA levels in less-invasive biological samples, such as the human fingernail, is suggested for the diagnosis and therapy of gout. Twenty-six healthy volunteers (HV) and 22 gout patients (GP) were studied. The UA was extracted from human fingernail samples, then separated on an Inertsil ODS-3 column (250 × 4.6 mm i.d., 4.0 μm, GL Sciences) by isocratic elution using methanol-74 mm phosphate buffer (pH 2.2) 2:98 (v/v). A UV detector was used to monitor the samples at 284 nm. Using the developed method, different UA concentrations were found in the GP and HV. When comparing the concentrations from GP with those from HV, a statistically significant correlation was observed between the UA (p < 0.01). In this study, the UA was confirmed as a potential biomarker for the diagnosis and therapy of gout. We have developed a novel sensitive, and simple method for the determination of UA in the fingernails of GP and HV. The human fingernail may serve as a noninvasive biosample for the diagnosis of gout. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26787501

  5. 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

  6. Effect of dehusked Garcinia kola seeds on the overall pharmacokinetics of quinine in healthy Nigerian volunteers.

    PubMed

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

    2015-03-01

    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 2 groups (A and B; n = 12 per group) on the basis of G. kola dose orally ingested. Each subject received 600 mg quinine sulfate before and after ingesting 12.5 g of G. kola once daily for 7 days (group A) or 12.5 g twice daily for 6 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 high performance liquid chromatography 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, respectively, 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

  7. Bioequivalence assay between orally disintegrating and conventional tablet formulations in healthy volunteers.

    PubMed

    Armando, Yara Popst; Schramm, Simone Grigoleto; Silva, Marina de Freitas; Kano, Eunice Kazue; Koono, Eunice Emiko Mori; Porta, Valentina; Serra, Cristina Helena dos Reis

    2009-01-21

    The purpose of this study was to evaluate bioequivalence of two commercial 8 mg tablet formulations of ondansetrona available in the Brazilian market. In this study, a simple, rapid, sensitive and selective liquid chromatography-tandem mass spectrometry method is described for the determination of ondansetron in human plasma samples. The method was validated over a concentration range of 2.5-60 ng/ml and used in a bioequivalence trial between orally disintegrating and conventional tablet ondansetron formulations, to assess its usefulness in this kind of study. Vonau flash (Biolab Sanus Farmacêutica, Brazil, as test formulations) and Zofran (GlaxoSmithKline, Brazil, as reference formulation) were evaluated following a single 8 mg dose to 23 healthy volunteers of both genders. The dose was administered after an overnight fast according to a two-way crossover design. Bioequivalence between the products was determinated by calculating 90% confidence interval (90% CI) for the ratio of C(max), AUC(0-t) and AUC(0-infinity) values for the test and reference products, using logarithmically transformed data. The 90% confidence interval for the ratio of C(max) (87.5-103.8%), AUC(0-t) (89.3-107.2%) and AUC(0-infinity) (89.7-106.0%) values for the test and reference products is within the 80-125% interval, proposed by FDA, EMEA and ANVISA. It was concluded that two ondansetron formulations are bioequivalent in their rate and extent of absorption. PMID:18848869

  8. A Pharmacometabonomic Approach To Predicting Metabolic Phenotypes and Pharmacokinetic Parameters of Atorvastatin in Healthy Volunteers.

    PubMed

    Huang, Qing; Aa, Jiye; Jia, Huning; Xin, Xiaoqing; Tao, Chunlei; Liu, Linsheng; Zou, Bingjie; Song, Qinxin; Shi, Jian; Cao, Bei; Yong, Yonghong; Wang, Guangji; Zhou, Guohua

    2015-09-01

    Genetic polymorphism and environment each influence individual variability in drug metabolism and disposition. It is preferable to predict such variability, which may affect drug efficacy and toxicity, before drug administration. We examined individual differences in the pharmacokinetics of atorvastatin by applying gas chromatography-mass spectrometry-based metabolic profiling to predose plasma samples from 48 healthy volunteers. We determined the level of atorvastatin in plasma using liquid chromatography-tandem mass spectrometry. With the endogenous molecules, which showed a good correlation with pharmacokinetic parameters, a refined partial least-squares model was calculated based on predose data from a training set of 36 individuals and exhibited good predictive capability for the other 12 individuals in the prediction set. In addition, the model was successfully used to predictively classify individual pharmacokinetic responses into subgroups. Metabolites such as tryptophan, alanine, arachidonic acid, 2-hydroxybutyric acid, cholesterol, and isoleucine were indicated as candidate markers for predicting by showing better predictive capability for explaining individual differences than a conventional physiological index. These results suggest that a pharmacometabonomic approach offers the potential to predict individual differences in pharmacokinetics and therefore to facilitate individualized drug therapy. PMID:26216528

  9. Clarithromycin substantially increases steady-state bosentan exposure in healthy volunteers

    PubMed Central

    Markert, Christoph; Schweizer, Yvonne; Hellwig, Regina; Wirsching, Theresia; Riedel, Klaus-Dieter; Burhenne, Juergen; Weiss, Johanna; Mikus, Gerd; Haefeli, Walter E

    2014-01-01

    Aims The aim of this study was to assess the effect of the cytochrome P450 (CYP) 3A4 and organic anion-transporting polypeptide (OATP) 1B1 inhibitor clarithromycin on the pharmacokinetics of bosentan. We also aimed to evaluate the impact of CYP2C9 and SLCO1B1 (encoding for OATP1B1) genotypes and their combination. Methods We assessed the effect of the OATP and CYP3A inhibitor clarithromycin on bosentan pharmacokinetics at steady state and concurrently quantified changes of CYP3A activity using midazolam as a probe drug. Sixteen healthy volunteers received therapeutic doses of bosentan (125 mg twice daily) for 14 days and clarithromycin (500 mg twice daily) concomitantly for the last 4 days, and bosentan pharmacokinetics was assessed on days 1, 10 and 14. Results Clarithromycin significantly increased bosentan area under the plasma concentration–time curve of the dosing interval 3.7-fold and peak concentration 3.8-fold in all participants irrespective of the genotype. Clarithromycin also reduced CYP3A activity (midazolam clearance) in all participants; however, these changes were not correlated to the changes of bosentan clearance. Conclusions Clarithromycin substantially increases the exposure to bosentan, suggesting that dose reductions may be necessary. PMID:23738582

  10. Time perception and its neuropsychological correlates in patients with schizophrenia and in healthy volunteers.

    PubMed

    Lee, Kwang-Hyuk; Bhaker, Rajinder S; Mysore, Ashok; Parks, Randolph W; Birkett, Paul B L; Woodruff, Peter W R

    2009-04-30

    Disordered time perception has been reported in schizophrenia. We investigated time perception dysfunction and its neuropsychological correlates in patients with schizophrenia. Participants comprised 38 patients and 38 age- and sex-matched healthy volunteers who were compared in an auditory temporal bisection paradigm using two interval ranges (a 400/800 ms condition and a 1000/2000 ms condition). In the temporal bisection, subjects were required to categorise a probe duration as short or long, based upon the similarity with two reference durations. All subjects also completed a battery of neuropsychological tests measuring sustained attention, short- and long-term memory and executive function. In the 400/800 ms condition, patients judged durations significantly shorter than did control subjects. Patients also exhibited decreased temporal sensitivity in both conditions. We found in both groups a negative association between temporal sensitivity and sustained attention for the 400/800 ms condition, and between temporal sensitivity and long-term memory for the 1000/200 ms condition. In patients, short-term memory performance was negatively associated with duration judgement in both conditions, while executive dysfunction was correlated to a general performance deficit in the 400/800 ms condition. These findings suggest the possibility that time perception abnormalities in schizophrenia are part of neuropsychological dysfunction and are likely to adversely impact upon activity of daily living. PMID:19278734

  11. Emission rates of selected volatile organic compounds from skin of healthy volunteers

    PubMed Central

    Mochalski, Paweł; King, Julian; Unterkofler, Karl; Hinterhuber, Hartmann; Amann, Anton

    2014-01-01

    Gas chromatography with mass spectrometric detection (GC–MS) coupled with solid phase micro-extraction as pre-concentration method (SPME) was applied to identify and quantify volatile organic compounds (VOCs) emitted by human skin. A total of 64 C4-C10 compounds were quantified in skin emanation of 31 healthy volunteers. Amongst them aldehydes and hydrocarbons were the predominant chemical families with eighteen and seventeen species, respectively. Apart from these, there were eight ketones, six heterocyclic compounds, six terpenes, four esters, two alcohols, two volatile sulphur compounds, and one nitrile. The observed median emission rates ranged from 0.55 to 4790 fmol cm−2 min−1. Within this set of analytes three volatiles; acetone, 6-methyl-5-hepten-2-one, and acetaldehyde exhibited especially high emission rates exceeding 100 fmol cm−2 min−1. Thirty-three volatiles were highly present in skin emanation with incidence rates over 80%. These species can be considered as potential markers of human presence, which could be used for early location of entrapped victims during Urban Search and Rescue Operations (USaR). PMID:24768920

  12. 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

  13. 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. PMID:19114096

  14. Pharmacokinetics, metabolism, and excretion of nefopam, a dual reuptake inhibitor in healthy male volunteers.

    PubMed

    Sanga, Madhu; Banach, John; Ledvina, Aaron; Modi, Nishit B; Mittur, Aravind

    2016-11-01

    1. The disposition of nefopam, a serotonin-norepinephrine reuptake inhibitor, was characterized in eight healthy male volunteers following a single oral dose of 75 mg [(14)C]-nefopam (100 μCi). Blood, urine, and feces were sampled for 168 h post-dose. 2. Mean (± SD) maximum blood and plasma radioactivity concentrations were 359 ± 34.2 and 638 ± 64.7 ngEq free base/g, respectively, at 2 h post-dose. Recovery of radioactive dose was complete (mean 92.6%); a mean of 79.3% and 13.4% of the dose was recovered in urine and feces, respectively. 3. Three main radioactive peaks were observed in plasma (metabolites M2 A-D, M61, and M63). Intact [(14)C]-nefopam was less than 5% of the total radioactivity in plasma. In urine, the major metabolites were M63, M2 A-D, and M51 which accounted for 22.9%, 9.8%, and 8.1% of the dose, respectively. An unknown entity, M55, was the major metabolite in feces (4.6% of dose). Excretion of unchanged [(14)C]-nefopam was minimal. PMID:26796604

  15. 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

  16. Bioequivalence study of two oral formulations of irbesartan 300 mg in healthy volunteers.

    PubMed

    Cánovas, M; Cabré, F; Polonio, F

    2014-01-01

    A bioequivalence study of 2 irbesartan (CAS 138402-11-6) film-coated tablet formulations was carried out in 40 healthy volunteers according to an open label, randomized, 2-period, 2-sequence, crossover, single dose and fasting conditions design. The test and reference formulations were administered in 2 treatment days, separated by a washout period of 7 days. Blood samples were drawn up to 96 h following drug administration. Plasma concentrations of irbesartan were obtained by a validated HPLC method using MS/MS detection. Log-transformed AUC0-t and Cmax values were tested for bioequivalence based on the ratios of the geometric LSmeans (test/reference). tmax was analysed nonparametrically. The 90% confidence intervals of the geometric LSmean values for the test/reference ratios for AUC0-t (98.06-109.48%, point estimator 103.61%) and Cmax (88.93-100.87%, point estimator 94.72%) were within the bioequivalence acceptance range of 80-125%. According to the European Guideline on the Investigation of Bioequivalence it may be therefore concluded that test formulation of irbesartan 300 mg film-coated tablet is bioequivalent to the reference formulation. Overall, it was judged that the study was conducted with a good tolerance of the subjects to both study drugs. PMID:24048950

  17. 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

  18. 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

  19. Cardiac metabolism during exercise in healthy volunteers measured by 31P magnetic resonance spectroscopy

    PubMed Central

    Conway, Michael A; Bristow, J David; Blackledge, Martin J; Rajagopalan, Bheeshma; Radda, George K

    1991-01-01

    A technique was devised for individuals to exercise prone in a magnet during magnetic resonance spectroscopy of the heart and phosphorus-31 magnetic resonance spectra of the heart were obtained by the phase modulated rotating frame imaging technique in six healthy volunteers during steady state dynamic quadriceps exercise. During prone exercise heart rate, blood pressure, and total body oxygen consumption were measured at increasing loads and the results were compared with those during Bruce protocol treadmill exercise. During prone exercise with a 5 kg load the heart rate was similar and the systolic and diastolic blood pressures were higher than those during stage 1 of the Bruce protocol. The rate-pressure products were similar but the total body oxygen consumption was lower during prone exercise. There was no difference in the ratio of phosphocreatine to adenosine triphosphate during rest and exercise. Thus during exercise that produced a local cardiac stress equal to or greater than that during stage 1 of the Bruce protocol treadmill exercise, the energy requirements of the normal human myocardium were adequately supplied by oxidative phosphorylation. PMID:1993127

  20. Cardiac metabolism during exercise in healthy volunteers measured by 31P magnetic resonance spectroscopy.

    PubMed

    Conway, M A; Bristow, J D; Blackledge, M J; Rajagopalan, B; Radda, G K

    1991-01-01

    A technique was devised for individuals to exercise prone in a magnet during magnetic resonance spectroscopy of the heart and phosphorus-31 magnetic resonance spectra of the heart were obtained by the phase modulated rotating frame imaging technique in six healthy volunteers during steady state dynamic quadriceps exercise. During prone exercise heart rate, blood pressure, and total body oxygen consumption were measured at increasing loads and the results were compared with those during Bruce protocol treadmill exercise. During prone exercise with a 5 kg load the heart rate was similar and the systolic and diastolic blood pressures were higher than those during stage 1 of the Bruce protocol. The rate-pressure products were similar but the total body oxygen consumption was lower during prone exercise. There was no difference in the ratio of phosphocreatine to adenosine triphosphate during rest and exercise.Thus during exercise that produced a local cardiac stress equal to or greater than that during stage 1 of the Bruce protocol treadmill exercise, the energy requirements of the normal human myocardium were adequately supplied by oxidative phosphorylation. PMID:1993127

  1. 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. PMID:26578361

  2. 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

  3. The brain signature of paracetamol in healthy volunteers: a double-blind randomized trial

    PubMed Central

    Pickering, Gisèle; Kastler, Adrian; Macian, Nicolas; Pereira, Bruno; Valabrègue, Romain; Lehericy, Stéphane; Boyer, Louis; Dubray, Claude; Jean, Betty

    2015-01-01

    Background Paracetamol’s (APAP) mechanism of action suggests the implication of supraspinal structures but no neuroimaging study has been performed in humans. Methods and results This randomized, double-blind, crossover, placebo-controlled trial in 17 healthy volunteers (NCT01562704) aimed to evaluate how APAP modulates pain-evoked functional magnetic resonance imaging signals. We used behavioral measures and functional magnetic resonance imaging to investigate the response to experimental thermal stimuli with APAP or placebo administration. Region-of-interest analysis revealed that activity in response to noxious stimulation diminished with APAP compared to placebo in prefrontal cortices, insula, thalami, anterior cingulate cortex, and periaqueductal gray matter. Conclusion These findings suggest an inhibitory effect of APAP on spinothalamic tracts leading to a decreased activation of higher structures, and a top-down influence on descending inhibition. Further binding and connectivity studies are needed to evaluate how APAP modulates pain, especially in the context of repeated administration to patients with pain. PMID:26229445

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

    PubMed

    Oo, Nwe Nwe; Bancone, Germana; 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

  5. 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

  6. 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

  7. 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.

  8. 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

  9. The disposition of bupropion and its metabolites in healthy male volunteers after single and multiple doses.

    PubMed

    Posner, J; Bye, A; Dean, K; Peck, A W; Whiteman, P D

    1985-01-01

    The pharmacokinetics of bupropion and 3 of its basic metabolites were determined in 8 young, healthy, male volunteers after single and multiple oral doses of bupropion. Plasma profiles were obtained: 1) after a single 100 mg oral dose of bupropion hydrochloride, 2) following administration of 100 mg 8-hourly for 14 days and 3) again after a single 100 mg dose 14 days later. Plasma concentrations of the parent drug and metabolites were determined by high-performance liquid chromatography. Saliva secretion and pupil diameters were measured, subjective assessments of sleep made using visual analogue scales and side effects, blood counts and biochemistry were monitored. After the first dose mean elimination half lives (t1/2) of bupropion, and metabolites I and II were 8, 19 and 19 h respectively. On repeated administration there was little accumulation of the parent drug and no evidence for induction of its own metabolism. Accumulation of I was consistent with its rate of elimination after single doses while that of II was greater than predicted with prolongation of t1/2 to 35 h. Metabolite III was barely detectable after single doses but its accumulation on multiple dosing was consistent with its long half life (35 h) determined on occasion 2. Saliva secretion was significantly reduced during the multiple dosing period but there were no complaints of dry mouth. Subjective assessments of sleep were not significantly altered though one subject reported vivid dreams. There were no other adverse reactions. PMID:3932079

  10. 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

  11. 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

  12. 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

  13. 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

  14. Safety and Tolerability of Panax ginseng Root Extract: A Randomized, Placebo-Controlled, Clinical Trial in Healthy Korean Volunteers

    PubMed Central

    Lee, Nam-Hun; Yoo, Sa-Ra; Kim, Hyeong-Geug; Cho, Jung-Hyo

    2012-01-01

    Abstract Objectives Panax ginseng has been extensively used as an adaptogen and is among the top 10 selling herbal supplements in the United States over the past decade. However, there have been few reports about the toxicity of P. ginseng in human studies. Given the lack of toxicological studies in human, this study investigated whether P. ginseng administration causes any noticeable toxic effects in healthy volunteers. Methods This study was designed as a randomized, double-blind, placebo-controlled, and parallel group trial in healthy volunteers. The subjects were required to be healthy, free from any significant disease, as assessed at screening by physical examination, medical history, and laboratory (hematological and biochemical) tests. Eligible subjects received P. ginseng extract (1 g/day or 2 g/day) or placebo over a 4-week period. Results Although mild adverse events, such as dyspepsia, hot flash, insomnia, and constipation, were reported in both P. ginseng and placebo group, no serious untoward reactions were reported following P. ginseng administration. Nonsignificant changes were observed in hematological and biochemical tests. Conclusions P. ginseng administration for 4 weeks was shown to be safe, tolerable, and free of any untoward toxic effect in healthy male and female volunteers. Future results from ongoing multicenter collaborative efforts to evaluate short- and long-term effects of P. ginseng may contribute to our current understanding of safety and tolerability of this herbal product. PMID:22909282

  15. 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

  16. Effects of GUASHA on Heart Rate Variability in Healthy Male Volunteers under Normal Condition and Weightlifters after Weightlifting Training Sessions

    PubMed Central

    Wang, Xingze; Chatchawan, Uraiwan; Nakmareong, Saowanee; Silsirivanit, Atit; Wang, Yingying; Xie, Dongbei; Yang, Jinsheng; Eungpinichpong, Wichai

    2015-01-01

    Objectives. This paper aims at exploring the effects of GUASHA on heart rate variability between healthy volunteers under normal condition and weightlifters after training sessions. Methods. Ten healthy male volunteers under normal condition and 15 male weightlifters after weightlifting training sessions were recruited into two groups. Electrocardiography was recorded before and immediately after 20-minute GUASHA. HRV was calculated in both the time domain and the frequency domain. Results. Stress index was reduced, while standard deviation of N-N intervals (SDNN), proportion derived by dividing the number of interval differences of successive N-N intervals greater than 50 ms, and root mean square of successive differences (RMSSD) were enhanced after GUASHA therapy in the two groups. The changes in SDNN and RMSSD were higher in the healthy men group than in the weightlifters group. In addition, low frequency was decreased whereas high frequency was significantly increased in healthy men after the GUASHA session. Conclusions. GUASHA therapy facilitates the parasympathetic nervous activity and modulates the balance between parasympathetic and sympathetic activities in both healthy men under normal condition and weightlifters after training sessions as indicated. Although the changes of the HRV parameters were similar in both groups, the responsiveness was more pronounced in healthy men than in male weightlifters. PMID:26120346

  17. 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

  18. 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

  19. Angina pectoris-like pain provoked by intravenous adenosine in healthy volunteers.

    PubMed

    Sylvén, C; Beermann, B; Jonzon, B; Brandt, R

    1986-07-26

    In a study to characterise the chest pain induced by adenosine this agent was given as a bolus into a peripheral vein to six healthy volunteers (five men) aged 30-44. On the first day the maximum tolerable dose was determined in each case. On the second day three doses of adenosine (one third, two thirds, and the full maximum tolerable dose) and three doses of saline were given single blind in randomised order. Thereafter aminophylline 5 mg/kg was given and the procedure repeated in a different randomised order. On the third day between two thirds and the full maximum tolerable dose was given followed by 10 mg dipyridamole intravenously and a second injection of the same dose of adenosine. Heart rate and atrioventricular blocks were recorded by electrocardiography. One minute after each dose of adenosine the chest pain was scored. The maximum tolerable dose of adenosine ranged from 10.6 to 37.1 mg. All subjects experienced uneasy central chest pain provoking anxiety. The pain radiated to the shoulders, ulnar aspect of the arms, epigastric area, back, and into the throat. The pain began about 20 seconds after the injection and lasted 10-15 seconds. Increasing the dose of adenosine increased the intensity of the pain. Administration of aminophylline reduced the pain significantly. Second degree heart block was recorded in five of the six subjects during the time that the pain was experienced. After aminophylline no block was observed. Dipyridamole increased the intensity of pain. The duration of second degree heart block increased in four of the subjects, and in two of these third degree heart block occurred. These findings suggest that adenosine released from the myocardium during ischaemia induces angina pectoris by stimulating theophylline sensitive receptors. PMID:3089465

  20. Effect of fosamprenavir/ritonavir on the pharmacokinetics of single-dose olanzapine in healthy volunteers.

    PubMed

    Jacobs, Birgit S; Colbers, Angela P H; Velthoven-Graafland, Kirsten; Schouwenberg, Bas J J W; Burger, David M

    2014-08-01

    Psychosis and other mental illnesses are common in HIV-infected patients. Olanzapine is one of the preferred antipsychotic agents for the treatment of schizophrenia. Olanzapine is primarily metabolised by CYP1A2 and uridine diphosphate glucuronosyltransferase (UGT). High-dose ritonavir has been shown to increase olanzapine elimination through induction of CYP1A2 and/or UGT, but the effect of low-dose ritonavir on olanzapine pharmacokinetics is unknown. Fosamprenavir is an HIV protease inhibitor that is boosted by low-dose ritonavir. To compensate for the induction of olanzapine metabolism by fosamprenavir/ritonavir, we hypothesised that a dose increase of olanzapine to 15 mg with fosamprenavir/ritonavir would lead to a similar area under the concentration-time curve (AUC) compared with olanzapine 10 mg alone. An open-label, randomised, two-period, cross-over, single-centre trial was conducted in 24 healthy volunteers. Subjects were randomised to one of the following treatments: (A) fosamprenavir/ritonavir 700/100 mg twice daily (b.i.d.) for 16 days with a single dose of olanzapine 15 mg on Day 13, a wash-out period of 31 days and a single dose of olanzapine 10 mg on Day 48; or (B) the same medication in reverse order. Twenty subjects completed the trial. The geometric mean ratios (90% CI) of olanzapine AUClast, maximum drug concentration (C(max)) and apparent elimination half-life (t(1/2)) when taken with fosamprenavir/ritonavir versus olanzapine alone were 1.00 (0.93-1.08), 1.32 (1.18-1.47) and 0.68 (0.63-0.74), respectively. Fosamprenavir/ritonavir 700/100 mg b.i.d. appeared to induce olanzapine metabolism. We therefore propose a 50% dosage increase of olanzapine when combining with a ritonavir-boosted protease inhibitor. PMID:24929949

  1. 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

  2. Oscillatory lower body negative pressure impairs task related functional hyperemia in healthy volunteers.

    PubMed

    Stewart, Julian M; Balakrishnan, Keshawadhana; Visintainer, Paul; Del Pozzi, Andrew T; Messer, Zachary R; Terilli, Courtney; Medow, Marvin S

    2016-03-15

    Neurovascular coupling refers to the link between an increase in neural activity in response to a task and an increase in cerebral blood flow denoted "functional hyperemia." Recent work on postural tachycardia syndrome indicated that increased oscillatory cerebral blood flow velocity (CBFv) was associated with reduced functional hyperemia. We hypothesized that a reduction in functional hyperemia could be causally produced in healthy volunteers by using oscillations in lower body negative pressure (OLBNP) to force oscillations in CBFv. CBFv was measured by transcranial Doppler ultrasound of the left middle cerebral artery. We used passive arm flexion applied during eight periodic 60-s flexion/60-s relaxation epochs to produce 120-s periodic changes in functional hyperemia (at 0.0083 Hz). We used -30 mmHg of OLBNP at 0.03, 0.05, and 0.10 Hz, the range for cerebral autoregulation, and measured spectral power of CBFv at all frequencies. Arm flexion power performed without OLBNP was compared with arm flexion power during OLBNP. OLBNP power performed in isolation was compared with power during OLBNP plus arm flexion. Cerebral flow velocity oscillations at 0.05 Hz reduced and at 0.10 Hz eliminated functional hyperemia, while 0.03 Hz did not reach significance. In contrast, arm flexion reduced OLBNP-induced oscillatory power at all frequencies. The interactions between OLBNP-driven CBFv oscillations and arm flexion-driven CBFv oscillations are reciprocal. Thus induced cerebral blood flow oscillations suppress functional hyperemia, and functional hyperemia suppresses cerebral blood flow oscillations. We conclude that oscillatory cerebral blood flow produces a causal reduction of functional hyperemia. PMID:26801310

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

    PubMed

    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) [(11)C]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 [(11)C]raclopride non-displaceable binding potential across the striatum. In the placebo group, re-exposure to stress led to smaller clusters of decreased [(11)C]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

  4. Benign elevations in serum aminotransferases and biomarkers of hepatotoxicity in healthy volunteers treated with cholestyramine

    PubMed Central

    2014-01-01

    Background There are currently no serum biomarkers capable of distinguishing elevations in serum alanine aminotransferase (ALT) that portend serious liver injury potential from benign elevations such as those occurring during cholestyramine treatment. The aim of the research was to test the hypothesis that newly proposed biomarkers of hepatotoxicity would not significantly rise in serum during elevations in serum ALT associated with cholestyramine treatment, which has never been associated with clinically relevant liver injury. Methods In a double-blind placebo-controlled trial, cholestyramine (8g) was administered for 11 days to healthy adult volunteers. Serum from subjects with elevations in alanine aminotransferase (ALT) exceeding three-fold the upper limit of normal (ULN) were utilized for biomarker quantification. Results In 11 of 67 subjects, cholestyramine treatment resulted in ALT elevation by >3x ULN (mean 6.9 fold; range 3–28 fold). In these 11 subjects, there was a 22.4-fold mean increase in serum levels of miR-122 relative to baseline, supporting a liver origin of the serum ALT. Significant elevations were noted in mean levels of necrosis biomarkers sorbitol dehydrogenase (8.1 fold), cytokeratin 18 (2.1 fold) and HMGB1 (1.7 fold). Caspase-cleaved cytokeratin 18, a biomarker of apoptosis was also significantly elevated (1.7 fold). A rise in glutamate dehydrogenase (7.3 fold) may support mitochondrial dysfunction. Conclusion All toxicity biomarkers measured in this study were elevated along with ALT, confirming the liver origin and reflecting both hepatocyte necrosis and apoptosis. Since cholestyramine treatment has no clinical liver safety concerns, we conclude that interpretation of the biomarkers studied may not be straightforward in the context of assessing liver safety of new drugs. PMID:25086653

  5. Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous and oral administration to healthy volunteers

    PubMed Central

    Nagelschmitz, J; Blunck, M; Kraetzschmar, J; Ludwig, M; Wensing, G; Hohlfeld, T

    2014-01-01

    Background The pharmacology of single doses of acetylsalicylic acid (ASA) administered intravenously (250 or 500 mg) or orally (100, 300, or 500 mg) was evaluated in a randomized, placebo-controlled, crossover study. Methods Blood and urine samples were collected before and up to 24 hours after administration of ASA in 22 healthy volunteers. Pharmacokinetic parameters and measurements of platelet aggregation were determined using validated techniques. Results A comparison between administration routes showed that the geometric mean dose-corrected peak concentrations (Cmax/D) and the geometric mean dose-corrected area under the curve (AUC0–∞/D) were higher following intravenous administration of ASA 500 mg compared with oral administration (estimated ratios were 11.23 and 2.03, respectively). Complete inhibition of platelet aggregation was achieved within 5 minutes with both intravenous ASA doses, reflecting a rapid onset of inhibition that was not observed with oral dosing. At 5 minutes after administration, the mean reduction in arachidonic acid-induced thromboxane B2 synthesis ex vivo was 99.3% with ASA 250 mg intravenously and 99.7% with ASA 500 mg intravenously. In exploratory analyses, thromboxane B2 synthesis was significantly lower after intravenous versus oral ASA 500 mg (P<0.0001) at each observed time point up to the first hour after administration. Concentrations of 6-keto-prostaglandin1α at 5 and 20 minutes after dosing were also significantly lower with ASA 500 mg intravenously than with ASA 500 mg orally. Conclusion This study demonstrates that intravenous ASA provides more rapid and consistent platelet inhibition than oral ASA within the first hour after dosing. PMID:24672263

  6. 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

  7. 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. PMID:18412024

  8. 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.

  9. Effects of increasing docosahexaenoic acid intake in human healthy volunteers on lymphocyte activation and monocyte apoptosis

    PubMed Central

    Mebarek, Saïda; Ermak, Natalia; Benzaria, Amal; Vicca, Stéphanie; Dubois, Madeleine; Némoz, Georges; Laville, Martine; Lacour, Bernard; Véricel, Evelyne; Lagarde, Michel; Prigent, Annie-France

    2009-01-01

    Dietary intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) has been reported to decrease several markers of lymphocyte activation and modulate monocyte susceptibility to apoptosis. However most human studies examined the combined effect of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) using relatively high daily amounts of n-3 PUFA. The present study investigated the effects of increasing doses of DHA added to the regular diet of human healthy volunteers on lymphocyte response to tetradecanoylphorbol acetate (TPA) plus ionomycin activation, and on monocyte apoptosis induced by oxidized LDL (oxLDL). Eight subjects were supplemented with increasing daily doses of DHA (200, 400, 800 and 1600mg) in a triacylglycerol form containing DHA as the only PUFA, for two weeks each dose. DHA intake dose-dependently increased the proportion of DHA in mononuclear cell phospholipids, the augmentation being significant after 400mg DHA/day. The TPA plus ionomycin-stimulated IL-2 mRNA level started to increase after ingestion of 400mg DHA/day, with a maximum after 800mg intake, and was positively correlated (P<0.003) with DHA enrichment in cell phospholipids. The treatment of monocytes by oxLDL before DHA supplementation drastically reduced mitochondrial membrane potential as compared with native LDL treatment. OxLDL apoptotic effect was significantly attenuated after 400mg DHA/day and the protective effect was maintained throughout the experiment, although to a lesser extent at higher doses. The present results show that supplementation of the human diet with low DHA dosages improves lymphocyte activability. It also increases monocyte resistance to oxLDL-induced apoptosis, which may be beneficial in the prevention of atherosclerosis. PMID:18710607

  10. Necessity and risks of arterial blood sampling in healthy volunteer studies.

    PubMed

    Oertel, Bruno Georg; Vermehren, Johannes; Zimmermann, Michael; Huynh, Thomas Tao; Doehring, Alexandra; Ferreiros, Nerea; Senzel, Stephan; Schmitz-Rixen, Thomas; Erbe, Matthias; Geisslinger, Gerd; Harder, Sebastian; Angst, Martin S; Lötsch, Jörn

    2012-10-01

    Arterial blood sampling is necessary when drugs such as the fast-acting opioid analgesic remifentanil exhibit relevant differences between arterial and venous blood concentrations. Arterial cannulation is generally considered to be clinically safe and has thus become a standard procedure in pharmacokinetic-pharmacodynamic assessments. However, rare cases of arterial occlusions have to be considered in risk-benefit assessments of arterial sampling in pharmacokinetic studies, especially when including healthy volunteers. In an actual case, arterial occlusion requiring surgical repair was caused by a factor V Leiden thrombophilia associated genetic variant F5 1691G>A (rs6025) and aggravated by a hypoplastic radial artery. Neither risk factor had been identified prior to enrolment by routine laboratory tests such as the prothrombin time (international normalized ratio), partial thromboplastin time and the clinical Allen's test of arterial function. Re-assessment of the necessity of arterial sampling showed that none of the potential alternatives, target concentrations of computerized infusions or venous concentrations during non-steady-state and steady-state conditions could provide the arterial concentrations. Relying on venous concentrations may result in erroneous pharmacodynamic parameters. Accurate pharmacokinetic-pharmacodynamic studies relying on precisely measured blood concentrations require serial sampling techniques during both steady-state and non-steady-state conditions. However, as illustrated by the presented case, incidents involving the generally safe procedure of arterial sampling are possible, although rare. To further minimize the risks, screening of subjects for prothrombotic risks and careful assessment of the suitability of the artery should be considered in pharmacokinetic studies requiring arterial cannulation. PMID:23018527