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Sample records for daily oral administration

  1. Safety, efficacy and patient satisfaction with continuous daily administration of levonorgestrel/ethinylestradiol oral contraceptives

    PubMed Central

    Benagiano, Giuseppe; Carrara, Sabina; Filippi, Valentina

    2009-01-01

    The progestational steroid norgestrel was synthesized and tested between 1960 and 1965 through an international cooperation between Wyeth, USA and Schering, Berlin. It is a mixture of two “enantiomers,” with only one form (designated as levonorgestrel) biologically active. When taken orally, it is rapidly absorbed, not subjected to a “first-pass” effect and is approximately 90% bioavailable, with a circulating half-life around 15 hours. Its contraceptive action is exerted at the central (hypothalamic) and peripheral (cervical mucus and endometrium) levels. Levonorgestrel (LNG), alone or in combination with ethinyl estradiol (EE), is the most widely employed contraceptive progestin: it is used in combined oral contraceptives, progestogen-only pills, long-acting contraceptive implants, intrauterine contraceptive systems and in emergency contraception. It is also the steroid of choice for new oral contraceptive regimens aimed at reducing the frequency of bleeding episodes. This novel approach, already tried more than 30 years ago, gained interest around the year 2000 when surveys of women’s attitudes toward monthly menstrual bleeding started to show a major change: more and more women declared that they would welcome a hormonal contraceptive method that reduced bleeding episodes to 4, 2 or even 1 per year. At this point, while the debate on the significance and “usefulness” of menstruation went on, attention focused on new regimens. The first new modality consisted of changing the 7-day medication-free interval, either shortening it to fewer than 7 days, or by the administration of low-dose estrogens during the interval between packages. Then, continuous administration regimens started to be investigated. This, however, did not happen suddenly, since, in specific situations, doctors had for years empirically utilized various continuous administration regimens. The first extended-cycle oral contraceptive regimen introduced in clinical practice is an 84

  2. 13-week repeated dose toxicity study of l-tyrosine in rats by daily oral administration.

    PubMed

    Shibui, Yusuke; Manabe, Yasuhiro; Kodama, Terutaka; Gonsho, Akinori

    2016-01-01

    To evaluate the potential toxicity of l-tyrosine, 4 groups of Crl:CD(SD) rats of both sexes were administered l-tyrosine in water suspension by gavage once daily for 13 weeks at doses of 0 (vehicle), 200, 600 or 2000 mg/kg bw/day. Findings related to l-tyrosine administration were as follows. Edema of the cornified layer at the limiting ridge or forestomach was seen in 600 mg/kg bw/day female group and in both sexes of 2000 mg/kg bw/day group. In the liver, increased weight and hypertrophy of centrilobular hepatocytes were seen in both sexes at 2000 mg/kg bw/day, associated with slight increases in ALT and AST. Regarding the kidney morphology and function, increased hyaline droplets in the proximal tubules and increased urinary protein were seen in the 2000 mg/kg bw/day male group. In addition, increased kidney weight was also observed in both sexes of the 2000 mg/kg bw/day group, although the histological changes attributable to the weight increase remained unclear. As for blood chemistry, increases in triglycerides, total cholesterol, phospholipids, potassium ion, calcium, total protein, and α1 globulin were also seen in both sexes at 2000 mg/kg bw/day. Thus, in this study the no-observed-adverse-effect level (NOAEL) of l-tyrosine was considered to be 600 mg/kg bw/day for males and 200 mg/kg bw/day for females. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Weekly vs. daily administration of oral methotrexate (MTX) for generalized plaque psoriasis: a randomized controlled clinical trial.

    PubMed

    Radmanesh, Mohammad; Rafiei, Behnam; Moosavi, Zahra-Beigum; Sina, Niloofar

    2011-10-01

    Methotrexate (MTX) treatment for psoriasis is most often administered weekly, because the drug has been considered more hepatotoxic when taken daily. However, some patients may tolerate smaller, more frequent doses better. To study the efficacy and toxicity of daily vs. weekly MTX. In a randomized controlled trial, 101 patients with generalized plaque psoriasis received oral MTX 2.5 mg daily for weeks, 4 weeks and monthly for a total of 4 months. Changes in PASI scores were classified into three categories: >75% improvement was considered significant; 25-75% moderate; and <25% poor. Sixty Group 1 patients and 81 Group 2 patients showed a significant response (P-value 0.001); 19 patients in Group 1 and 14 in Group 2 responded moderately; 22 patients in Group 1 and six patients from Group 2 responded poorly. Forty-five patients in Group 1 and 33 in Group 2 developed transient increases in liver enzymes (P-value 0.11). Nausea, headache, fatigue, and gastrointestinal upset were noted in four Group 1 patients and 30 Group 2 patients (P-value 0.0001). Nausea, vomiting, headache, and fatigue were significantly less common side effects in our patients who received MTX daily, but liver enzyme abnormalities were less common, and clinical efficacy was greater in the patients who received MTX weekly. © 2011 The International Society of Dermatology.

  4. Penetration of levofloxacin into skin tissue after oral administration of multiple 750 mg once-daily doses.

    PubMed

    Chow, A T; Chen, A; Lattime, H; Morgan, N; Wong, F; Fowler, C; Williams, R R

    2002-04-01

    To probe the pharmacokinetic basis for the use of levofloxacin for complicated skin and skin-structure infections (SSSIs) at a once-daily dosage of 750 mg by investigating its penetration into skin tissue. Ten healthy volunteers were administered three oral, once-daily 750 mg doses of levofloxacin, and levofloxacin concentrations were subsequently measured over time (0.5-24 h) in skin-punch biopsy tissue and plasma. Skin tissue concentrations consistently exceeded those in plasma at every time point, with tissue/plasma ratios of 1.37 +/- 0.81 for peak concentration and 1.97 +/- 0.35 for area under the concentration versus time curve. Three of the ten subjects reported treatment-emergent adverse events (AEs) that were considered unrelated to treatment. An 11th subject who had enrolled in the study withdrew after AEs of mild severity that were possibly related to the study drug. The results support the clinical usage of levofloxacin 750 mg once-daily for complicated SSSIs.

  5. A method for reliable voluntary oral administration of a fixed dosage (mg/kg) of chronic daily medication to rats.

    PubMed

    Corbett, Adrian; McGowin, Audrey; Sieber, Scott; Flannery, Tiffany; Sibbitt, Bethany

    2012-10-01

    Stress can influence a number of physiological processes including adult neurogenesis, metabolism, cardiovascular function, immune function, neurophysiological function, endocrine function and inflammatory processes following injury. In testing drugs which may be used to treat various diseases or injuries, reducing stress associated with chronic drug delivery to animal models should then be an imperative, which led us to design a reliable voluntary oral drug delivery method. Various drug combinations were tested versus vehicle controls in four different rat stocks or strains (Wistar, Fisher, Long Evans and Sprague Dawley) with our voluntary oral delivery system. Oral medications were placed into a store-bought sugar cookie dough ball (~4 g), thoroughly integrating the dry drugs with the dough. This method has worked consistently to deliver the medication (complete ingestion) in four different stocks or strains of rats, with reliabilities ranging from 98.6% to 100%. The percentage of rats in each stock or strain that have at any time during the study had incomplete ingestion of the drugs ranged from 1% in Sprague Dawley, approximately 4% in Wistar and Fisher, to approximately 16% in Long Evans. Both serum and brain samples were analysed for high-performance liquid chromatography (HPLC) detection of one of our administered drugs: 5 mg/kg fluoxetine. HPLC analysis shows that serum levels are detectable 2-4 h after ingestion, but not 24 h after ingestion. Brain samples however, showed detectable levels of both fluoxetine and norfluoxetine more than a week following ingestion of a single dose, with higher norfluoxetine levels seen following a month of daily administered drugs.

  6. Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats.

    PubMed

    Choi, Jia; Ryu, Su-Jung; Kim, Kui-Jin; Kim, Hyung-Min; Chung, Hee-Chul; Lee, Boo-Yong

    2018-01-20

    Gelidium elegans extract (GEE) is derived from a red alga from the Asia-Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD) rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted <2 days. Therefore, the LD 50 of GEE is likely to be >5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL) for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

  7. Treatment of chemotherapy-induced neutropenia in a rat model by using multiple daily doses of oral administration of G-CSF-containing nanoparticles.

    PubMed

    Su, Fang-Yi; Chuang, Er-Yuan; Lin, Po-Yen; Chou, Yi-Chun; Chen, Chiung-Tong; Mi, Fwu-Long; Wey, Shiaw-Pyng; Yen, Tzu-Chen; Lin, Kun-Ju; Sung, Hsing-Wen

    2014-04-01

    Chemotherapy-induced neutropenia often increases the likelihood of life-threatening infections. In this study, a nanoparticle (NP) system composed of chitosan and poly(γ-glutamic acid) conjugated with diethylene triamine pentaacetic acid (γPGA-DTPA) was prepared for oral delivery of granulocyte colony-stimulating factor (G-CSF), a hematopoietic growth factor. The therapeutic potential of this NP system for daily administration of G-CSF to treat neutropenia associated with chemotherapy was evaluated in a rat model. In vitro results indicate that the procedures of NP loading and release preserved the structural integrity and bioactivity of the G-CSF molecules adequately. Those results further demonstrated the enzymatic inhibition activity of γPGA-DTPA towards G-CSF against intestinal proteases. Additionally, the in vivo biodistribution study clearly identified accumulations of G-CSF in the heart, liver, bone marrow, and urinary bladder, an indication of systemic absorption of G-CSF; its relative bioavailability was approximately 13.6%. Moreover, significant glucose uptake was observed in bone marrow during G-CSF treatment, suggesting increased bone marrow metabolism and neutrophil production. Consequently, neutrophil count in the blood increased in a sustained manner; this fact may help a patient's immune system recover from the side effects of chemotherapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Differential Effects of Silver Nanoparticles and Silver Ions on Tissue Accumulation, Distribution, and Toxicity in the Sprague Dawley Rat Following Daily Oral Gavage Administration for 13 Weeks

    PubMed Central

    Boudreau, Mary D.; Imam, Mohammed S.; Paredes, Angel M.; Bryant, Matthew S.; Cunningham, Candice K.; Felton, Robert P.; Jones, Margie Y.; Davis, Kelly J.; Olson, Greg R.

    2016-01-01

    There are concerns within the regulatory and research communities regarding the health impact associated with consumer exposure to silver nanoparticles (AgNPs). This study evaluated particulate and ionic forms of silver and particle size for differences in silver accumulation, distribution, morphology, and toxicity when administered daily by oral gavage to Sprague Dawley rats for 13 weeks. Test materials and dose formulations were characterized by transmission electron microscopy (TEM), dynamic light scattering, and inductively coupled mass spectrometry (ICP-MS). Seven-week-old rats (10 rats per sex per group) were randomly assigned to treatments: AgNP (10, 75, and 110 nm) at 9, 18, and 36 mg/kg body weight (bw); silver acetate (AgOAc) at 100, 200, and 400 mg/kg bw; and controls (2 mM sodium citrate (CIT) or water). At termination, complete necropsies were conducted, histopathology, hematology, serum chemistry, micronuclei, and reproductive system analyses were performed, and silver accumulations and distributions were determined. Rats exposed to AgNP did not show significant changes in body weights or intakes of feed and water relative to controls, and blood, reproductive system, and genetic tests were similar to controls. Differences in the distributional pattern and morphology of silver deposits were observed by TEM: AgNP appeared predominantly within cells, while AgOAc had an affinity for extracellular membranes. Significant dose-dependent and AgNP size-dependent accumulations were detected in tissues by ICP-MS. In addition, sex differences in silver accumulations were noted for a number of tissues and organs, with accumulations being significantly higher in female rats, especially in the kidney, liver, jejunum, and colon. PMID:26732888

  9. Voluntary Oral Administration of Losartan in Rats.

    PubMed

    Diogo, Lucília N; Faustino, Inês V; Afonso, Ricardo A; Pereira, Sofia A; Monteiro, Emília C; Santos, Ana I

    2015-09-01

    Gavage is a widely performed technique for daily dosing in laboratory rodents. Although effective, gavage comprises a sequence of potentially stressful procedures for laboratory animals that may introduce bias into experimental results, especially when the drugs to be tested interfere with stress-dependent parameters. We aimed to test vehicles suitable for drug delivery by voluntary ingestion in rats. Specifically, Male Wistar rats (age, 2 to 3 mo) were used to test nut paste (NUT), peanut butter (PB), and sugar paste (SUG) as vehicles for long-term voluntary oral administration of losartan, an angiotensin II receptor blocker. Vehicles were administered for 28 d without drug to assess effects on the glucose level and serum lipid profile. Losartan was mixed with vehicles and either offered to the rats or administered by gavage (14 d) for subsequent quantification of losartan plasma levels by HPLC. After a 2-d acclimation period, all rats voluntarily ate the vehicles, either alone or mixed with losartan. NUT administration reduced blood glucose levels. The SUG group had higher concentrations of losartan than did the gavage group, without changes in lipid and glucose profiles. Our results showed that NUT, PB, and SUG all are viable for daily single-dose voluntary ingestion of losartan and that SUG was the best alternative overall. Drug bioavailability was not reduced after voluntary ingestion, suggesting that this method is highly effective for chronic oral administration of losartan to laboratory rodents.

  10. Voluntary Oral Administration of Losartan in Rats

    PubMed Central

    Diogo, Lucília N; Faustino, Inês V; Afonso, Ricardo A; Pereira, Sofia A; Monteiro, Emília C; Santos, Ana I

    2015-01-01

    Gavage is a widely performed technique for daily dosing in laboratory rodents. Although effective, gavage comprises a sequence of potentially stressful procedures for laboratory animals that may introduce bias into experimental results, especially when the drugs to be tested interfere with stress-dependent parameters. We aimed to test vehicles suitable for drug delivery by voluntary ingestion in rats. Specifically, Male Wistar rats (age, 2 to 3 mo) were used to test nut paste (NUT), peanut butter (PB), and sugar paste (SUG) as vehicles for long-term voluntary oral administration of losartan, an angiotensin II receptor blocker. Vehicles were administered for 28 d without drug to assess effects on the glucose level and serum lipid profile. Losartan was mixed with vehicles and either offered to the rats or administered by gavage (14 d) for subsequent quantification of losartan plasma levels by HPLC. After a 2-d acclimation period, all rats voluntarily ate the vehicles, either alone or mixed with losartan. NUT administration reduced blood glucose levels. The SUG group had higher concentrations of losartan than did the gavage group, without changes in lipid and glucose profiles. Our results showed that NUT, PB, and SUG all are viable for daily single-dose voluntary ingestion of losartan and that SUG was the best alternative overall. Drug bioavailability was not reduced after voluntary ingestion, suggesting that this method is highly effective for chronic oral administration of losartan to laboratory rodents. PMID:26424254

  11. Daily oral iron supplementation during pregnancy

    PubMed Central

    Peña-Rosas, Juan Pablo; De-Regil, Luz Maria; Dowswell, Therese; Viteri, Fernando E

    2014-01-01

    Background Iron and folic acid supplementation has been the preferred intervention to improve iron stores and prevent anaemia among pregnant women, and it may also improve other maternal and birth outcomes. Objectives To assess the effects of daily oral iron supplements for pregnant women, either alone or in conjunction with folic acid, or with other vitamins and minerals as a public health intervention. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (2 July 2012). We also searched the WHO International Clinical Trials Registry Platform (ICTRP) (2 July 2012) and contacted relevant organisations for the identification of ongoing and unpublished studies. Selection criteria Randomised or quasi-randomised trials evaluating the effects of oral preventive supplementation with daily iron, iron + folic acid or iron + other vitamins and minerals during pregnancy. Data collection and analysis We assessed the methodological quality of trials using standard Cochrane criteria. Two review authors independently assessed trial eligibility, extracted data and conducted checks for accuracy. Main results We included 60 trials. Forty-three trials, involving more than 27,402 women, contributed data and compared the effects of daily oral supplements containing iron versus no iron or placebo. Overall, women taking iron supplements were less likely to have low birthweight newborns (below 2500 g) compared with controls (8.4% versus 10.2%, average risk ratio (RR) 0.81; 95% confidence interval (CI) 0.68 to 0.97, 11 trials, 8480 women) and mean birthweight was 30.81 g greater for those infants whose mothers received iron during pregnancy (average mean difference (MD) 30.81; 95% CI 5.94 to 55.68, 14 trials, 9385 women). Preventive iron supplementation reduced the risk of maternal anaemia at term by 70% (RR 0.30; 95% CI 0.19 to 0.46, 14 trials, 2199 women) and iron deficiency at term by 57% (RR 0.43; 95% CI 0.27 to 0.66, seven trials, 1256 women

  12. The efficacy and safety of docetaxel-based chemotherapy combined with dexamethasone 1 mg daily oral administration: JMTO Pca 10-01 phase II trial.

    PubMed

    Tanaka, Nobumichi; Nishimura, Kazuo; Okajima, Eijiro; Ina, Kenji; Ogawa, Osamu; Nagata, Hirohiko; Akakura, Koichiro; Fujimoto, Kiyohide; Gotoh, Momokazu; Teramukai, Satoshi; Hirao, Yoshihiko

    2017-03-01

    Previously, one randomized control trial (TAX327) revealed the efficacy of docetaxel-based chemotherapy combined with prednisone. On the other hand, several studies showed a high prostate specific antigen (PSA) response with low-dose dexamethasone in castration-resistant prostate cancer (CRPC) patients. The objective of this study was to evaluate the efficacy and safety of docetaxel-based chemotherapy combined with dexamethasone in CRPC patients. This study was a single-arm multi-institutional phase II trial. Patients received 75 mg/m2 of docetaxel, and 0.5 mg of dexamethasone orally twice a day continuing throughout the treatment period. Treatment was planned for 10 cycles, and continued for at least four cycles depending on the observation of PSA flare. The primary endpoint was PSA response defined as a reduction from baseline of at least 50% that continued for at least 3 weeks. Secondary endpoints were safety, PSA flare, time to PSA failure and adherence rate to protocol treatment (10 cycles). Between January 2011 and February 2014, a total of 76 chemotherapy-naïve CRPC patients were enrolled. Seventy-five patients received docetaxel-based chemotherapy combined with dexamethasone. The median age and PSA level at enrollment were 71 years (53-85) and 23.2 ng/mL (2.9-852), respectively. PSA response rate was 76.8% (90% confidence interval (CI): 66.9-84.9). Of all patients, 30 patients completed 10 cycles of chemotherapy (40%). The incidence rate of PSA flare was 10.7% (eight patients). The median time to PSA failure was 369 days (95% CI: 245-369). The most frequently observed adverse event was hematotoxicity (neutropenia of G2 or greater: 100%). The present study showed a significantly high PSA response compared with previous reports. Most patients tolerated the protocol treatment well, whereas hematotoxicity was often observed. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Comparisons of l-cysteine and d-cysteine toxicity in 4-week repeated-dose toxicity studies of rats receiving daily oral administration.

    PubMed

    Shibui, Yusuke; Sakai, Ryosei; Manabe, Yasuhiro; Masuyama, Takeshi

    2017-07-01

    Two 4-week repeated-dose toxicity studies were conducted to evaluate the potential toxicity of l-cysteine and d-cysteine. In one study, three groups of 6 male rats were each administered l-cysteine once daily by gavage at doses of 500, 1,000, or 2,000 mg/kg/day for 28 consecutive days. The control group was administered a 0.5% methylcellulose vehicle solution. The other study followed a similar protocol except that the experimental groups received d-cysteine. Toxicological observations showed that the l-cysteine-treated groups exhibited renal injuries such as basophilic tubules with eosinophilic material in the lumen, and there were increased numbers of basophilic tubules in all treated groups. In 1,000 or 2,000 mg/kg/day-treated groups, salivation and necropsy findings indicative of focal erosion in the stomach mucosa were found. Increases in reticulocyte counts were observed in the 2,000 mg/kg/day-treated group. Toxicological findings obtained for the d-cysteine-treated groups included anemia and renal injuries such as basophilic tubules with eosinophilic material in the lumen, increased numbers of basophilic tubules, and crystal deposition in the medulla in the 2,000 mg/kg/day-treated group. Additional findings included sperm granuloma in the epididymis, necropsy findings suggestive of focal erosion in the stomach mucosa, and salivation in the 1,000 or 2,000 mg/kg/day-treated groups. One rat in the 2,000 mg/kg/day-treated group died due to renal failure. In conclusion, the no-observed-adverse-effect levels (NOAELs) were estimated to be less than 500 mg/kg/day for l-cysteine and 500 mg/kg/day for d-cysteine under our study conditions. The toxicological profiles were similar for l-cysteine and d-cysteine; however, there were slight differences in the dose responses. The mechanisms underlying these differences remain to be determined.

  14. Administration of Injectable Vitamin K Orally.

    PubMed

    Afanasjeva, Janna

    2017-10-01

    Background: Vitamin K, or phytonadione, is available in both injectable and oral formulations. Oral vitamin K is available as 5-mg tablets, but the key drawbacks for using vitamin K tablets consist of availability of only 1 dose strength and recent tripling of the product's cost over a 2-year period. An interest exists for utilization of injectable vitamin K via oral route. Method: A literature search was performed on April 26, 2017, to identify any studies describing the use of injectable vitamin K for oral administration. The search involved PubMed and Embase and utilized various combinations of keywords vitamin K , phytonadione , IV , intravenous , injectable , and oral . The results were limited to studies that discussed oral administration of injectable vitamin K. The efficacy of the injectable preparation of vitamin K administered orally was explored in 6 studies and one cost-savings project. Results: Based on the available literature, the administration of injectable vitamin K via oral route is effective and safe. Injectable vitamin K for oral administration can be prepared as an undiluted solution or as a compounded solution. These 2 formulations have different beyond-use dates depending on ingredients used. Conclusion: Information on efficacy and stability of injectable vitamin K formulations prepared for oral administration provides an additional option for health care systems when vitamin K tablets are unavailable or cost-prohibitive to use.

  15. A dose-ranging study evaluating once-daily oral administration of the factor Xa inhibitor rivaroxaban in the treatment of patients with acute symptomatic deep vein thrombosis: the Einstein-DVT Dose-Ranging Study.

    PubMed

    Buller, Harry R; Lensing, Anthonie W A; Prins, Martin H; Agnelli, Giancarlo; Cohen, Alexander; Gallus, Alexander S; Misselwitz, Frank; Raskob, Gary; Schellong, Sebastian; Segers, Annelise

    2008-09-15

    We performed a randomized dose-ranging study, double-blind for rivaroxaban doses and open-label for the comparator (low-molecular-weight heparin followed by vitamin K antagonists) to assess the optimal dose of rivaroxaban for the treatment of deep vein thrombosis. A total of 543 patients with acute deep-venous thrombosis received rivaroxaban 20, 30, or 40 mg once daily or comparator. Treatment lasted for 84 days. The primary efficacy outcome was the 3-month incidence of the composite of symptomatic venous thromboembolic complications and asymptomatic deterioration in thrombotic burden as assessed by comparison of ultrasound and perfusion lung scanning at day 84 with baseline. The main safety outcome was the composite of major bleeding and clinically relevant nonmajor bleeding. A total of 449 (83%) of the 543 patients could be included in the per-protocol population. The primary efficacy outcome occurred in 6.1%, 5.4%, and 6.6% of the rivaroxaban 20-, 30-, and 40-mg treatment groups, respectively, and in 9.9% of those receiving standard therapy. The main safety outcome occurred in 5.9%, 6.0%, and 2.2% of the rivaroxaban 20-, 30-, and 40-mg treatment groups, respectively, and in 8.8% of those receiving standard therapy. These results with simple fixed-dose oral regimens justify phase 3 evaluations (www.ClinicalTrials.gov no.NCT00395772).

  16. Induction of testicular damage by daily methamphetamine administration in rats.

    PubMed

    Lin, Ji-Fan; Lin, Yi-Hsuan; Liao, Po-Cheng; Lin, Yi-Chia; Tsai, Te-Fu; Chou, Kuang-Yu; Chen, Hung-En; Tsai, Shiow-Chwen; Hwang, Thomas I-Sheng

    2014-02-28

    Methamphetamine (METH)-induced brain damage and apoptosis within the central nervous system are well documented. This study was conducted to investigate the toxic effects of daily METH administration on the testes in a rat model. Male Sprague-Dawley rats (5 weeks old, ~100 g, n = 64) were divided into two groups and treated with vehicle (saline, control) or METH (10 mg/kg) for 15, 30, 60 and 90 days. The results showed that daily administration of METH decreased the body, testicular and epididymis weights as well as the serum levels of total testosterone. The increased apoptotic index (Bad/Bcl2 expression ratio) and levels of cleaved caspase-3 indicated that apoptosis had occurred in the testes of the METH-treated rats. The oxidative stress levels increased as the reduced and oxidized glutathione (GSH/GSSG) ratio decreased. The overall sperm counts decreased at 15 and 90 days, where- as morphologically abnormal sperm counts increased at 30, 60 and 90 days in the METH-treated rats. This study demonstrates that daily exposure to METH significantly reduced the number and quality of sperm in rats. The underlying pathophysiological mechanisms likely include the reduction of serum testosterone levels and the increase of oxidative stress and apoptosis in the rat testes.

  17. Endocrinological effects of single daily ketoconazole administration in male beagle dogs.

    PubMed

    De Coster, R; Beerens, D; Dom, J; Willemsens, G

    1984-10-01

    Some endocrinological effects of single daily oral administration of 150 mg ketoconazole for 15 days were investigated in 4 male beagle dogs. Plasma testosterone fell markedly within 3-4 h and then progressively returned to control concentrations by 10 h after drug administration. On the other hand, plasma 17 alpha-hydroxyprogesterone, progesterone and 17 alpha, 20 alpha-dihydroxyprogesterone increased within 3-10 h before returning to basal values after 24 h. Plasma LH did not rise significantly though some high individual levels were noted. Plasma cortisol and oestradiol-17 alpha levels were not significantly modified by the treatment. These results confirm that a high therapeutic dose of ketoconazole, given orally once a day, transiently inhibits in vivo the 17-20 lyase enzyme of the testis, without modifying basal cortisol and oestradiol-17 beta plasma concentrations and that enzymatic inhibition still occurs after daily treatment for up to 2 weeks but remains transient and parallels the resorption profile of the drug so that normal plasma testosterone levels are observed from 10 to 24 h after drug intake. However, permanent inhibition of androgen biosynthesis might be obtained by the administration of high doses of ketoconazole given several times a day.

  18. Around-the-clock oral THC effects on sleep in male chronic daily cannabis smokers.

    PubMed

    Gorelick, David A; Goodwin, Robert S; Schwilke, Eugene; Schroeder, Jennifer R; Schwope, David M; Kelly, Deanna L; Ortemann-Renon, Catherine; Bonnet, Denis; Huestis, Marilyn A

    2013-01-01

    Δ9-tetrahydrocannabinol (THC) promotes sleep in animals; clinical use of THC is associated with somnolence. Human laboratory studies of oral THC have not shown consistent effects on sleep. We prospectively evaluated self-reported sleep parameters during controlled oral THC administration to research volunteers. Thirteen male chronic daily cannabis smokers (mean ± SD age 24.6± 3.7 years, self-reported smoking frequency of 5.5 ± 5.9 (range 1-24) joint-equivalents daily at study entry) were administered oral THC doses (20 mg) around-the-clock for 7 days (40-120 mg daily) starting the afternoon after admission. The St. Mary's Hospital Sleep Questionnaire was completed every morning. Plasma THC and 11-OH-THC (active metabolite) concentrations were measured in venous blood samples collected every evening. Changes in sleep characteristics over time and associations between sleep characteristics and plasma cannabinoid concentrations were evaluated with repeated measures mixed linear regression. Higher evening THC and 11-OH-THC concentrations were significantly associated with shorter sleep latency, less difficulty falling asleep, and more daytime sleep the following day. In contrast, the duration of calculated and self-reported nighttime sleep decreased slightly (3.54 and 5.34 minutes per night, respectively) but significantly during the study. These findings suggest that tolerance to the somnolent effects of THC may have occurred, but results should be considered preliminary due to design limitations. Somnolence from oral THC may dissipate with chronic, high-dose use. This has implications for patients who may take chronic oral THC for medicinal purposes, including cannabis dependence treatment. (Am J Addict 2013;22:510-514). Copyright © American Academy of Addiction Psychiatry.

  19. Pharmacokinetics of total thyroxine in dogs after administration of an oral solution of levothyroxine sodium.

    PubMed

    Le Traon, G; Burgaud, S; Horspool, L J I

    2008-04-01

    Oral L-thyroxine (L-T4) supplementation is used to replace thyroid hormone concentrations in dogs with hypothyroidism. The pharmacokinetics of L-T4 following administration of a solution (Leventa) was investigated in healthy dogs. L-T4 was absorbed fairly rapidly (t(max) 3 h). A mean bioavailability of 22% was calculated following a single oral administration of 40 microg L-T4/kg body weight. Repeated oral administration at the same dose for 14 consecutive days did not lead to any accumulation of T4 in serum. After intravenous administration of L-T4, a serum half-life of 11.6 h was calculated. Food intake concomitant with L-T4 oral administration delayed L-T4 absorption and decreased its rate and extent by about 45%. The relative bioavailability of L-T4 following administration of a tablet formulation was about 50% of that of the L-T4 solution. The pharmacokinetic properties of liquid L-T4 after oral administration support the use of a dose rate of 20 microg/kg once daily, as a starting dose for replacement therapy in dogs with hypothyroidism.

  20. Oral impacts on daily performances and recent use of dental services in schoolchildren.

    PubMed

    Monsantofils, Monica; Bernabé, Eduardo

    2014-11-01

    To explore whether oral impacts on daily performances are related to recent use of dental services among children and whether oral impacts on specific daily performances are more strongly related to recent use of dental services. Data from a cross-sectional survey, including 805 11-12-year-old children attending four randomly selected schools in Lima (Peru), were used. The child version of the oral impacts on daily performances (Child-OIDP) was used to assess prevalence, intensity, and extent of oral impacts. Use of dental services was assessed by self-reports of last dental visit and reason for the visit. Associations of the prevalence, intensity, and extent of oral impacts with use of dental services were tested in logistic regression models. Children with oral impacts were 1.99 (95% CI: 1.17-3.37) times more likely to have used dental services recently than their counterparts. The intensity and extent of oral impacts were linearly associated with children's use of dental services. Difficulties in eating were the only type of oral impacts on daily performances associated with use of dental services, independent of children's demographic characteristics, and impacts on other performances. Oral impacts on daily performances were related to recent use of dental services among these schoolchildren. © 2013 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. In Vitro Activity and Fecal Concentration of Rifaximin after Oral Administration

    PubMed Central

    Jiang, Zhi-Dong; Ke, Shi; Palazzini, Ernesto; Riopel, Lise; Dupont, Herbert

    2000-01-01

    Rifaximin showed moderately high MICs (the MIC at which 90% of the isolates tested were inhibited = 50 μg/ml) for 145 bacterial enteropathogens from patients with traveler's diarrhea acquired in Mexico during the summers of 1997 and 1998. Rifaximin concentrations in stool the day after oral administration (800 mg daily for 3 days) were high (average, 7,961 μg/g), proving the value of the drug. PMID:10898704

  2. Pharmacokinetics of paracetamol (acetaminophen) after intravenous and oral administration.

    PubMed

    Rawlins, M D; Henderson, D B; Hijab, A R

    1977-04-20

    Plasma paracetamol concentrations were measured in 6 volunteers after single intravenous (1000 mg) and oral (500 mg, 1000 mg and 2000 mg) doses of the drug. Paracetamol levels declined multiphasically with a mean clearance after intravenous administration of 352 +/- 40 ml/min. A two-compartment open model appeared to describe the decline adequately. Comparison of the areas under the plasma concentration-time curves (AUC) indicated that oral bioavailability increased from 0.63 +/- 0.02 after 500 mg, to 0.89 +/- 0.04 and 0.87 +/- 0.08 after 1000 mg and 2000 mg, respectively. As a consequence of the incomplete bioavailability of paracetamol, as well as its multicompartmental distribution, accurate estimates of its distribution volume and clearance cannot be obtained if the drug is given orally. However, an estimate of its total plasma clearance may be derived from the AUC after a 500 mg oral dose.

  3. Oral Fluid and Plasma Cannabinoid Ratios after Around-the-Clock Controlled Oral Δ9-Tetrahydrocannabinol Administration

    PubMed Central

    Milman, Garry; Schwope, David M.; Schwilke, Eugene W.; Darwin, William D.; Kelly, Deanna L.; Goodwin, Robert S.; Gorelick, David A.; Huestis, Marilyn A.

    2013-01-01

    BACKGROUND Oral fluid (OF) testing is increasingly important for drug treatment, workplace, and drugged-driving programs. There is interest in predicting plasma or whole-blood concentrations from OF concentrations; however, the relationship between these matrices is incompletely characterized because of few controlled drug-administration studies. METHODS Ten male daily cannabis smokers received around-the-clock escalating 20-mg oral Δ9-tetrahydrocannabinol (THC, dronabinol) doses (40–120 mg/day) for 8 days. Plasma and OF samples were simultaneously collected before, during, and after dosing. OF THC, 11-hydroxy-THC and 11-nor-9-carboxy-THC (THCCOOH) were quantified by GC-MS at 0.5-μg/L, 0.5-μg/L, and 7.5-ng/L limits of quantification (LOQs), respectively. In plasma, the LOQs were 0.25 μg/L for THC and THCCOOH, and 0.5 μg/L for 11-hydroxy-THC. RESULTS Despite multiple oral THC administrations each day and increasing plasma THC concentrations, OF THC concentrations generally decreased over time, reflecting primarily previously self-administered smoked cannabis. The logarithms of the THC concentrations in oral fluid and plasma were not significantly correlated (r = −0.10; P = 0.065). The OF and plasma THCCOOH concentrations, albeit with 1000-fold higher concentrations in plasma, increased throughout dosing. The logarithms of OF and plasma THCCOOH concentrations were significantly correlated (r = 0.63; P < 0.001), although there was high interindividual variation. A high OF/plasma THC ratio and a high OF THC/THCCOOH ratio indicated recent cannabis smoking. CONCLUSIONS OF monitoring does not reliably detect oral dronabinol intake. The time courses of THC and THCCOOH concentrations in plasma and OF were different after repeated oral THC doses, and high inter-individual variation was observed. For these reasons, OF cannabinoid concentrations cannot predict concurrent plasma concentrations. PMID:21875944

  4. Pharmacokinetics of tilmicosin after oral administration in swine.

    PubMed

    Shen, Jianzhong; Li, Cun; Jiang, Haiyang; Zhang, Suxia; Guo, Ping; Ding, Shuangyang; Li, Xiaowei

    2005-06-01

    To determine the pharmacokinetics of tilmicosin after oral administration of a single dose of tilmicosin base in swine. 10 healthy swine. Tilmicosin base was administered via stomach tube at a single dose of 20 mg/kg (n = 5) or 40 mg/kg (5). Blood samples were obtained from a jugular vein immediately before and at 10, 20, and 30 minutes and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours after administration of tilmicosin. Tilmicosin concentrations in serum were quantified by use of a high-performance liquid chromatography procedure with UV light. Data for tilmicosin concentrations versus time were analyzed by use of compartmental and noncompartmental methods. Tilmicosin concentrations in serum decreased in a biexponential manner after oral administration. Mean +/- SD values for absorption half-lives were 1.49 +/- 0.23 hours and 1.64 +/- 0.40 hours, distribution half-lives were 2.96 +/- 0.58 hours and 3.20 +/- 0.76 hours, elimination half-lives were 25.26 +/- 8.25 and 20.69 +/- 5.07 hours, peak concentrations were 1.19 +/- 0.30 microg/mL and 2.03 +/- 0.28 microg/mL, and time to peak concentrations was 3.12 +/- 0.50 hours and 3.48 +/- 0.77 hours after oral administration of tilmicosin base at a single dose of 20 or 40 mg/kg, respectively. In swine, tilmicosin was rapidly absorbed and slowly eliminated after oral administration of a single dose of tilmicosin base powder.

  5. The prevalence and severity of oral impacts on daily performances in Thai primary school children

    PubMed Central

    Gherunpong, Sudaduang; Tsakos, Georgios; Sheiham, Aubrey

    2004-01-01

    Background Traditional methods of measuring oral health mainly use clinical dental indices and have been complemented by oral health related quality of life (OHRQoL) measures. Most OHRQoL studies have been on adults and elderly populations. There are no systematic OHRQoL studies of a population-based sample of children. The objective of this study was to assess the prevalence, characteristics and severity of oral impacts in primary school children. Methods Cross-sectional study of all 1126 children aged 11–12 years in a municipal area of Suphanburi province, Thailand. An OHRQoL measure, Child-Oral Impacts on Daily Performances index (Child-OIDP) was used to assess oral impacts. Children were also clinically examined and completed a self-administered questionnaire about demographic information and oral behaviours. Results 89.8% of children had one or more oral impacts. The median impact score was 7.6 and mean score was 8.8. Nearly half (47.0%) of the children with impacts had impacts at very little or little levels of intensity. Most (84.8%) of those with impacts had 1–4 daily performances affected (out of 8 performances). Eating was the most common performance affected (72.9%). The severity of impacts was high for eating and smiling and low for study and social contact performances. The main clinical causes of impacts were sensitive tooth (27.9%), oral ulcers (25.8%), toothache (25.1%) and an exfoliating primary tooth (23.4%). Conclusions The study reveals that oral health impacts on quality of life in Thai primary school children. Oral impacts were prevalent, but not severe. The impacts mainly related to difficulty eating and smiling. Toothache, oral ulcers and natural processes contributed largely to the incidence of oral impacts. PMID:15476561

  6. Cross-cultural differences in oral impacts on daily performance between Greek and British older adults.

    PubMed

    Tsakos, G; Marcenes, W; Sheiham, A

    2001-12-01

    To examine whether there are significant cross-cultural differences in oral health-related quality of life and perceived treatment need between older people of similar clinical oral status living in Greece and Britain. Cross-sectional surveys of adults living independently aged 65 years or older. In Britain, data from the national diet and nutrition survey were used, while the Greek sample was drawn from two municipalities in Athens. Participants 753 in Britain and 681 in Greece. Oral health-related quality of life, assessed through the modified Oral Impacts on Daily Performance (OIDP) indicator, and perceived need for dental treatment. Thirty-nine per cent of Greek and 12.3% of British dentate and 47.6% of Greek and 16.3% of British edentulous participants had experienced oral impacts affecting their daily life in the last six months. The most prevalent impact was difficulty eating. Apart from that, 56.3% of Greek and 37.1% of British dentate and 33.5% of Greek and 25.3% of British edentulous participants perceived dental treatment need. After controlling for sociodemographic variables, perceived general health and clinical oral status, Greek dentate and edentulous participants were significantly more likely to experience oral impacts than their British counterparts, while in relation to perceived treatment need significant cross-cultural differences existed only between dentate respondents. The results indicated an independent cultural influence in the perception of oral impacts in older people.

  7. Pharmacokinetics of valproic acid after oral and intravenous administration

    PubMed Central

    Perucca, E.; Gatti, G.; Frigo, G. M.; Crema, A.

    1978-01-01

    1 The kinetics of sodium valproate (di-n-propyl-acetate, Depakine®) have been studied in six healthy volunteers after administration of single oral and intravenous doses (800 mg). 2 Kinetic parameters were similar for both routes of administration. In all subjects absorption was rapid and complete. Half-lives ranged from 11-15 h. Apparent volumes of distribution were relatively low (0.147 ± 0.004 l/kg) and showed little variation amongst individuals. 3 The factors responsible for the poor correlation between dosage and serum levels during chronic treatment and therapeutic implications are discussed.

  8. Azathioprine pharmacokinetics after intravenous, oral, delayed release oral and rectal foam administration.

    PubMed Central

    Van Os, E C; Zins, B J; Sandborn, W J; Mays, D C; Tremaine, W J; Mahoney, D W; Zinsmeister, A R; Lipsky, J J

    1996-01-01

    BACKGROUND: 6-Mercaptopurine and its prodrug azathioprine are effective medications for refractory inflammatory bowel disease. However, use of these drugs has been limited by concerns about their toxicity. Colonic delivery of azathioprine may reduce its systemic bioavailability and limit toxicity. AIM: To determine the bioavailability of 6-mercaptopurine after administration of azathioprine via three colonic delivery formulations. METHODS: Twenty four healthy human subjects each received 50 mg of azathioprine by one of four delivery formulations (each n = 6): oral; delayed release oral; hydrophobic rectal foam; and hydrophilic rectal foam. All subjects also received a 50 mg dose of intravenous azathioprine during a separate study period. Plasma concentrations of 6-mercaptopurine were determined by high pressure liquid chromatography. RESULTS: The bioavailabilities of 6-mercaptopurine after colonic azathioprine administration via delayed release oral, hydrophobic rectal foam, and hydrophilic rectal foam (7%, 5%, 1%; respectively) were significantly lower than the bioavailability of 6-mercaptopurine after oral azathioprine administration (47%) by Wilcoxon rank sum pairwise comparison. CONCLUSIONS: Azathioprine delivered to the colon by delayed release oral and rectal foam formulations considerably reduced systemic 6-mercaptopurine bioavailability. The therapeutic potential of these colonic delivery methods, which can potentially limit toxicity by local delivery of high doses of azathioprine, should be investigated in patients with inflammatory bowel disease. PMID:8881811

  9. Pharmacokinetic Comparison of Once-Daily Topical Minocycline Foam 4% vs Oral Minocycline for Moderate-to-Severe Acne.

    PubMed

    Jones, Terry M; Ellman, Herman; deVries, Tina

    2017-10-01

    To characterize minocycline pharmacokinetics and relative bioavailability following multiple-dose topical administration of minocycline hydrochloride (HCl) foam 4% (FMX101 4%) as compared with single-dose oral administration of minocycline HCl extended-release tablets (Solodyn®) in subjects with moderate-to-severe acne. A Phase 1, single-center, nonrandomized, open-label, active-controlled, 2-period, 2-treatment crossover clinical study. The study included 30 healthy adults (mean age, 22.6 years; 90% white, and 60% females) who had moderate-to-severe acne. Subjects were assigned to first receive a single oral dose of a minocycline HCl extended-release tablet (approximately 1 mg/kg). At 10 days after the oral minocycline dose, topical minocycline foam 4% was applied, once daily for 21 days. Serial blood samples were obtained before and after administration of oral minocycline and each topical application of minocycline foam 4% on days 1, 12, and 21. Following oral administration of minocycline (approximately 1 mg/kg), plasma minocycline concentration increased until 3 hours, followed by a log-linear decrease over the remainder of the 96-hour sampling period. Following topical application of a 4-g maximal-use dose of minocycline foam 4% for 21 days, plasma minocycline concentration was very low, with geometric mean Cmax values ranging from 1.1 ng/mL to 1.5 ng/mL. Steady state was achieved by day 6. Overall, minocycline exposure with topical minocycline foam 4% was 730 to 765 times lower than that with oral minocycline. There was no evidence of minocycline accumulation over the 21 days of topical application of minocycline foam 4%. Topical minocycline foam 4% appeared to be safe and well tolerated, with no serious treatment-emergent adverse events (TEAEs), treatment-related TEAEs, or TEAEs that led to treatment discontinuation. Once-daily topical application of minocycline foam 4% did not lead to significant systemic exposure to minocycline. It appears to be a well

  10. Anti-cancer activity of bromelain nanoparticles by oral administration.

    PubMed

    Bhatnagar, Priyanka; Patnaik, Soma; Srivastava, Amit K; Mudiam, Mohan K R; Shukla, Yogeshwer; Panda, Amulya K; Pant, Aditya B; Kumar, Pradeep; Gupta, Kailash C

    2014-12-01

    Oral administration of anti-cancer drugs is an effective alternative to improve their efficacy and reduce undesired toxicity. Bromelain (BL) is known as an effective anti-cancer phyto-therapeutic agent, however, its activity is reduced upon oral administration. In addressing the issue, BL was encapsulated in Poly(lactic-co-glycolic acid) (PLGA) to formulate nanoparticles (NPs). Further, the NPs were coated with Eudragit L30D polymer to introduce stability against the gastric acidic conditions. The resultant coated NPs were characterized for BL entrapment, proteolytic activity and mean particle size. The stability and release pattern of NPs were evaluated under simulated gastrointestinal tract (GIT) pH conditions. Cytotoxicity studies carried out in human cell lines of diverse origin have shown significant dose advantage (-7-10 folds) with NPs in reducing the IC50 values compared with free BL. The cellular uptake of NPs in MCF-7, HeLa and Caco-2 cells monolayer was significantly enhanced several folds as compared to free BL. Altered expression of marker proteins associated with apoptosis and cell death (P53, P21, Bcl2, Bax) also confirmed the enhanced anti-carcinogenic potential of formulated NPs. Oral administration of NPs reduced the tumor burden of Ehrlich ascites carcinoma (EAC) in Swiss albino mice and also increased their life-span (160.0 ± 5.8%) when compared with free BL (24 ± 3.2%). The generation of reactive oxygen species, induction of apoptosis and impaired mitochondrial membrane potential in EAC cells treated with NPs confirmed the suitability of Eudragit coated BL-NPs as a promising candidate for oral chemotherapy.

  11. The effect of high-dose dronabinol (oral THC) maintenance on cannabis self-administration.

    PubMed

    Schlienz, Nicolas J; Lee, Dustin C; Stitzer, Maxine L; Vandrey, Ryan

    2018-06-01

    There is a clear need for advancing the treatment of cannabis use disorders. Prior research has demonstrated that dronabinol (oral THC) can dose-dependently suppress cannabis withdrawal and reduce the acute effects of smoked cannabis. The present study was conducted to evaluate whether high-dose dronabinol could reduce cannabis self-administration among daily users. Non-treatment seeking daily cannabis users (N = 13) completed a residential within-subjects crossover study and were administered placebo, low-dose dronabinol (120 mg/day; 40 mg tid), or high-dose dronabinol (180-240 mg/day; 60-80 mg tid) for 12 consecutive days (order counterbalanced). During each 12-day dronabinol maintenance phase, participants were allowed to self-administer smoked cannabis containing <1% THC (placebo) or 5.7% THC (active) under forced-choice (drug vs. money) or progressive ratio conditions. Participants self-administered significantly more active cannabis compared with placebo in all conditions. When active cannabis was available, self-administration was significantly reduced during periods of dronabinol maintenance compared with placebo maintenance. There was no difference in self-administration between the low- and high-dose dronabinol conditions. Chronic dronabinol dosing can reduce cannabis self-administration in daily cannabis users and suppress withdrawal symptoms. Cannabinoid agonist medications should continue to be explored for therapeutic utility in the treatment of cannabis use disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Effects of Once-Daily Oral and Transdermal Methylphenidate on Sleep Behavior of Children with ADHD

    ERIC Educational Resources Information Center

    Faraone, Stephen V.; Glatt, Stephen J.; Bukstein, Oscar G.; Lopez, Frank A.; Arnold, L. Eugene; Findling, Robert L.

    2009-01-01

    Objective: Methylphenidate is a leading first-line treatment for ADHD (AD/HD). This stimulant has long been suspected to adversely affect sleeping patterns of treated individuals, especially children. There are few studies on the effects of recently developed longer-acting methylphenidate treatments, such as once-daily oral or transdermal…

  13. The relationship between initial route of heroin administration and speed of transition to daily heroin use.

    PubMed

    Hines, Lindsey A; Lynskey, Michael; Morley, Katherine I; Griffiths, Paul; Gossop, Michael; Powis, Beverly; Strang, John

    2017-09-01

    The effect of heroin administration route on speed of transition to regular use is unknown. This paper aims to determine whether the speed of transition from initiation of heroin use to daily heroin use differs by route of administration (injecting, chasing/inhaling or snorting). Privileged access interviewer survey of purposively selected sample of 395 current people who use heroin (both in and not in treatment) in London, UK (historical sample from 1991). Data on age and year of initiation, time from initiation to daily use and routes of administration were collected by means of a structured questionnaire. Generalised ordered logistic models were used to test the relationship between route of initial administration of heroin and speed of transition to daily heroin use. Analyses were adjusted for gender, ethnicity, daily use of other drug(s) at time of initiation, year of initiation and treatment status at interview. After adjustment, participants whose initial administration route was injecting had a 4.71 (95% confidence interval 1.34-16.5) increase in likelihood of progressing to daily use within 1-3 weeks of initiation, compared to those whose initial administration route was non-injecting. The speed of transition from first use to daily heroin use is faster if the individual injects heroin at initiation of use. Those who initiate heroin use through injecting have a shorter time frame for intervention before drug use escalation. [Hines LA, Lynskey M, Morley KI, Griffiths P, Gossop M, Powis B, Strang J. The relationship between initial route of heroin administration and speed of transition to daily heroin use. Drug Alcohol Rev 2017;00:000-000]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

  14. Qualitative analysis of the impact of Oral Potentially Malignant Disorders on daily life activities.

    PubMed

    Tadakamadla, Jyothi; Kumar, Santhosh; Lalloo, Ratilal; Johnson, Newell W

    2017-01-01

    To evaluate the impact of Oral Potentially Malignant Disorders (OPMD) on daily life activities. Patients diagnosed with Oral Leukoplakia, Oral submucous fibrosis and Oral Lichen Planus attending the Oral Medicine clinic of Panineeya Institute of Dental Sciences & Research Centre, Hyderabad, India were invited to participate. Eighteen interviews and three focus groups were conducted in a non-clinical setting. Voice recordings were transcribed and translated from Telugu to English. Data coding was performed using the NVivo software. Sample size for this qualitative study comprised 32 patients. Four main themes emerged: (1) difficulties with diagnosis and knowledge about the condition, (2) physical impairment and functional limitations, (3) psychological and social wellbeing and (4) effects of treatment on daily life. In a majority of the patients, most of the interview time was spent discussing physical impairment and functional limitations. Patients also reported their mouth condition having a debilitating effect on their psychological well-being and social interactions. 'Physical impairment and functional limitations' was the most important theme for many of the patients. However, the impacts of OPMD also extended beyond physical impairment and functional limitations to aspects of daily living, notably psychological and social wellbeing.

  15. Pressor response to oral tyramine during co-administration with safinamide in healthy volunteers.

    PubMed

    Di Stefano, Andrea Francesco Daniele; Rusca, Antonio

    2011-12-01

    The aim of this study was to evaluate the pressor response to oral tyramine during repeated administration of oral safinamide in healthy volunteers. Twelve females and eight males aged 52.7 ± 4.9 years entered the study. An oral tyramine screening test was conducted to select subjects sensitive to the tyramine pressor effect on systolic blood pressure (SBP) in the dose range of 200-400 mg. Safinamide 300 mg was then administered once daily under fasting conditions. Starting on day 5 (safinamide pharmacokinetic steady state), single ascending doses of tyramine were co-administered daily: 50, 100 and 200 mg were administered on days 5, 6 and 7, respectively. Vital parameters were monitored by telemetry. No SBP increase ≥30 mmHg over baseline was observed when tyramine was co-administered with safinamide. Less than one third of the 400 mg responders reported SBP increases between 22 and 27 mmHg, which were below the threshold of 30 mmHg over baseline. SBP increases, as well as time interval to pressor response measured after co-treatment with safinamide and tyramine 200 mg, were not significantly different from those measured after administration of oral tyramine 200 mg alone. Safinamide 300 mg, administered o.d. under fasting conditions, does not change the tyramine pressor response as evaluated at steady state after 6-7 days of treatment as compared with the effect of tyramine administered alone. Safinamide, which inhibits monoamine oxidase (MAO)-B, does not affect oral tyramine metabolism mediated mostly by the intestinal MAO-A.

  16. Brain kinetics of methylphenidate (Ritalin) enantiomers after oral administration.

    PubMed

    Ding, Yu-Shin; Gatley, S John; Thanos, Panayotis K; Shea, Colleen; Garza, Victor; Xu, Youwen; Carter, Pauline; King, Payton; Warner, Don; Taintor, Nicholas B; Park, Daniel J; Pyatt, Bea; Fowler, Joanna S; Volkow, Nora D

    2004-09-01

    Methylphenidate (MP) (Ritalin) is widely used for the treatment of attention deficit hyperactivity disorder (ADHD). It is a chiral drug, marketed as the racemic mixture of d- and l-threo enantiomers. Our previous studies (PET and microdialysis) in humans, baboons, and rats confirm the notion that pharmacological specificity of MP resides predominantly in the d-isomer. A recent report that intraperitoneally (i.p.) administered l-threo-MP displayed potent, dose-dependent inhibition of cocaine- or apomorphine-induced locomotion in rats, raises the question of whether l-threo-MP has a similar effect when given orally. It has been speculated that l-threo-MP is poorly absorbed in humans when it is given orally because of rapid presystemic metabolism. To investigate whether l-threo-MP or its metabolites can be delivered to the brain when it is given orally, and whether l-threo-MP is pharmacologically active. PET and MicroPET studies were carried out in baboons and rats using orally delivered C-11-labeled d- and l-threo-MP ([methyl-(11)C]d-threo-MP and [methyl-(11)C]l-threo-MP). In addition, we assessed the effects of i.p. l-threo-MP on spontaneous and cocaine-stimulated locomotor activity in mice. There was a higher global uptake of carbon-11 in both baboon and rat brain for oral [(11)C]l-threo-MP than for oral [(11)C]d-threo-MP. Analysis of the chemical form of radioactivity in rat brain after [(11)C]d-threo-MP indicated mainly unchanged tracer, whereas with [(11)C]l-threo-MP, it was mainly a labeled metabolite. The possibility that this labeled metabolite might be [(11)C]methanol or [(11)C]CO(2), derived from demethylation, was excluded by ex vivo studies in rats. When l-threo-MP was given i.p. to mice at a dose of 3 mg/kg, it neither stimulated locomotor activity nor inhibited the increased locomotor activity due to cocaine administration. These results suggest that, in animal models, l-threo-MP or its metabolite(s) is (are) absorbed from the gastrointestinal tract and

  17. [Effects of preoperative oral carbohydrate administration on gastric contents].

    PubMed

    Sato, Chiaki; Shibuya, Hiromi; Nishino, Miho; Maeda, Akihiko; Shimakawa, Noriko; Okada, Toshiki

    2012-08-01

    Preoperative oral carbohydrate administration for adult patients has been recommended by European Society for Parenteral and Enteral Nutrition and Enhanced Recovery After Surgery. Although preoperative oral carbohydrate may improve patient satisfaction and perioperative glucose metabolism, its effects on the gastric contents remain controversial. We included 232 adult patients without gastrointestinal stenosis or occlusion. Seventy-four patients (group A) were not permitted to eat or drink before operation for eight hours, while 158 patients (group B) took oral carbohydrate (225 ml, 22.3% glucose) two hours before anesthesia induction. After induction, gastric contents were aspirated to examine its volume and pH. Although the mean volume of gastric contents of the patients in group B was significantly lower than that in group A, and gastric pH was also significantly smaller in group B, no patients suffered from aspiration during rapid induction. Fasting interval and gastric volume were inversely related, and almost all the patients with fasting interval above 150 minutes showed gastric contents volume smaller than 25 ml and gastric pH more than 2.5. We conclude that preoperative oral carbohydrate can be given safely, although the fasting interval should be 150 minutes in our diet regimen.

  18. Effect of oral ketoconazole on first-pass effect of nifedipine after oral administration in dogs.

    PubMed

    Kuroha, Masanori; Kayaba, Hideki; Kishimoto, Shizuka; Khalil, Waleed F; Shimoda, Minoru; Kokue, Eiichi

    2002-03-01

    The long-term oral ketoconazole (KTZ) treatment extensively inhibits hepatic CYP3A activity. We investigated the effect of the KTZ treatment on hepatic and intestinal extraction of nifedipine (NIF) using beagle dogs. Four dogs were given orally KTZ for 20 days (200 mg, bid). NIF was administered either intravenously (0.5 mg/kg) or orally (20 mg) 10 and 20 days before the KTZ treatment and 10 and 20 days after start of KTZ treatment. CLtot of NIF after intravenous administration decreased to about 50% during the KTZ treatment. C(max) and AUC after oral administration increased to 2.5-fold and fourfold, respectively, by the KTZ treatment. The hepatic extraction ratio of NIF decreased to about a half by KTZ. A significant decrease in intestinal extraction ratio was not observed. In conclusion, the KTZ treatment inhibits hepatic extraction more profoundly than intestinal extraction of NIF. Therefore, inhibition of hepatic extraction of NIF by the KTZ treatment mainly results in substantial increase in systemic bioavailability in dogs. Because KTZ inhibits human CYP3A activities similar to canine CYP3A activities, the long-term oral KTZ treatment may dramatically increase bioavailability of NIF or other CYP3A substrates in humans. Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association.

  19. Safety of 8-weeks oral administration of Arctium lappa L.

    PubMed

    Bok, So-Hyeon; Cho, Seung Sik; Bae, Chun-Sik; Park, Dae-Hun; Park, Kyung-Mok

    2017-09-01

    Recently, worldwide dietary reference intakes have been considered an important guideline for public health. Some governments and the World Health Organization (WHO) provide guidelines concerning dietary intake. Although an ingredient may have a history of use as a culinary material, changes in the environment over time suggest that the acceptable maximum intake each of food/culinary material should be regularly evaluated. Arctium lappa L. has been used as a culinary material for many centuries in Korea and Japan and some recent studies have reported related therapeutic effects. However, there are no reports on the safety of repeated oral administration. In this study, we evaluated the safety of a 8-weeks repeated oral intake of A. lappa . We concluded that treatment with <250 mg/kg A. lappa , which was within the safety range, resulted in body weight decrease and blood glucose suppression.

  20. Safety of 8-weeks oral administration of Arctium lappa L.

    PubMed Central

    Bok, So-Hyeon; Cho, Seung Sik; Bae, Chun-Sik

    2017-01-01

    Recently, worldwide dietary reference intakes have been considered an important guideline for public health. Some governments and the World Health Organization (WHO) provide guidelines concerning dietary intake. Although an ingredient may have a history of use as a culinary material, changes in the environment over time suggest that the acceptable maximum intake each of food/culinary material should be regularly evaluated. Arctium lappa L. has been used as a culinary material for many centuries in Korea and Japan and some recent studies have reported related therapeutic effects. However, there are no reports on the safety of repeated oral administration. In this study, we evaluated the safety of a 8-weeks repeated oral intake of A. lappa. We concluded that treatment with <250 mg/kg A. lappa, which was within the safety range, resulted in body weight decrease and blood glucose suppression. PMID:29046701

  1. Cannabinoids and metabolites in expectorated oral fluid after 8 days of controlled around-the-clock oral THC administration.

    PubMed

    Milman, Garry; Barnes, Allan J; Schwope, David M; Schwilke, Eugene W; Goodwin, Robert S; Kelly, Deana L; Gorelick, David A; Huestis, Marilyn A

    2011-08-01

    Oral fluid (OF) is an increasingly accepted matrix for drug testing programs, but questions remain about its usefulness for monitoring cannabinoids. Expectorated OF specimens (n = 360) were obtained from 10 adult daily cannabis smokers before, during, and after 37 20-mg oral Δ(9)-tetrahydrocannabinol (THC) doses over 9 days to characterize cannabinoid disposition in this matrix. Specimens were extracted and analyzed by gas chromatography-mass spectrometry with electron-impact ionization for THC, 11-hydroxy-THC, cannabidiol, and cannabinol, and negative chemical ionization for 11-nor-9-carboxy-THC (THCCOOH). Linear ranges for THC, 11-hydroxy-THC, and cannabidiol were 0.25-50 ng/mL; cannabinol 1-50 ng/mL; and THCCOOH 5-500 pg/mL. THCCOOH was the most prevalent analyte in 344 specimens (96.9%), with concentrations up to 1,390.3 pg/mL. 11-hydroxy-THC, cannabidiol, and cannabinol were detected in 1, 1, and 3 specimens, respectively. THC was detected in only 13.8% of specimens. The highest THC concentrations were obtained at admission (median 1.4 ng/mL, range 0.3-113.6) from previously self-administered smoked cannabis. A total of 2.5 and 3.7% of specimens were THC-positive at the recommended Substance Abuse and Mental Health Services Administration (2 ng/mL) and Driving Under the Influence of Drugs, Alcohol and Medicines (DRUID) (1 ng/mL) confirmation cutoffs, respectively. THC is currently the only analyte for monitoring cannabis exposure in OF; however, these data indicate chronic therapeutic oral THC administration and illicit oral THC use are unlikely to be identified with current guidelines. Measurement of THCCOOH may improve the detection and interpretation of OF cannabinoid tests and minimize the possibility of OF contamination from passive inhalation of cannabis smoke.

  2. Cannabinoids and metabolites in expectorated oral fluid after 8 days of controlled around-the-clock oral THC administration

    PubMed Central

    Milman, Garry; Barnes, Allan J.; Schwope, David M.; Schwilke, Eugene W.; Goodwin, Robert S.; Kelly, Deana L.; Gorelick, David A.

    2013-01-01

    Oral fluid (OF) is an increasingly accepted matrix for drug testing programs, but questions remain about its usefulness for monitoring cannabinoids. Expectorated OF specimens (n=360) were obtained from 10 adult daily cannabis smokers before, during, and after 37 20-mg oral Δ9-tetrahydrocannabinol (THC) doses over 9 days to characterize cannabinoid disposition in this matrix. Specimens were extracted and analyzed by gas chromatography– mass spectrometry with electron-impact ionization for THC, 11-hydroxy-THC, cannabidiol, and cannabinol, and negative chemical ionization for 11-nor-9-carboxy-THC (THCCOOH). Linear ranges for THC, 11-hydroxy-THC, and cannabidiol were 0.25–50 ng/mL; cannabinol 1–50 ng/mL; and THCCOOH 5–500 pg/mL. THCCOOH was the most prevalent analyte in 344 specimens (96.9%), with concentrations up to 1,390.3 pg/mL. 11-hydroxy-THC, cannabidiol, and cannabinol were detected in 1, 1, and 3 specimens, respectively. THC was detected in only 13.8% of specimens. The highest THC concentrations were obtained at admission (median 1.4 ng/mL, range 0.3–113.6) from previously self-administered smoked cannabis. A total of 2.5 and 3.7% of specimens were THC-positive at the recommended Substance Abuse and Mental Health Services Administration (2 ng/mL) and Driving Under the Influence of Drugs, Alcohol and Medicines (DRUID) (1 ng/mL) confirmation cutoffs, respectively. THC is currently the only analyte for monitoring cannabis exposure in OF; however, these data indicate chronic therapeutic oral THC administration and illicit oral THC use are unlikely to be identified with current guidelines. Measurement of THCCOOH may improve the detection and interpretation of OF cannabinoid tests and minimize the possibility of OF contamination from passive inhalation of cannabis smoke. PMID:21637933

  3. Distribution of creatinine following intravenous and oral administration to rats.

    PubMed

    Watanabe, J; Hirate, J; Iwamoto, K; Ozeki, S

    1981-05-01

    To evaluate the distribution of creatinine in rats, urinary, fecal and expiratory excretion, plasma levels and whole-body autoradiography following intravenous or oral administration of [carbonyl-14C]creatinine was investigated. More than 90% of the exogeneous creatinine was excreted in the urine in 24 hr following intravenous administration, and both fecal and expiratory excretion were only about 1%. In case of oral administration, however, it was found that expiratory excretion could not be neglected, ranging from about 1 to 30%. Plasma creatinine concentration-time curves following the intravenous administration (70.4 micrograms/kg or 400 mg/kg as creatinine) were analyzed according to a two-compartment open model. There were significant but very small differences in the pharmacokinetic parameters for these two doses. When these parameters were compared with those of urea, k12 and k21, which are transfer rate constants between compartment 1 and 2, for creatinine were significantly smaller than those of urea. On the other hand, k10 was larger in creatinine. Furthermore, (V'd)extrap for creatinine was about three times that of urea. Whole-body autoradiograms at 5 minutes following intravenous administration showed that exogeneous creatinine distributes with higher concentrations in liver, lung and kidney than in muscle and fat. This results was remarkably different from that of urea which distributes almost uniformly throughout the body at the same time. This difference observed in the autoradiograms would be the consequence of the fact that urea has larger k12 and k21 than creatinine.

  4. "Las Charlas" como expresion oral diaria ["Chats" as Daily Oral Practice].

    ERIC Educational Resources Information Center

    Borden, Matt

    2002-01-01

    An oral practice system of "chats" in the classroom functions as an extemporaneous speaking exercise or chat (without notes or prompt sheets), occurring between two students for a minute or so at the beginning of class, following which the presenters respond to other students' questions. (CNP)

  5. Oxycodone physical dependence and its oral self-administration in C57BL/6J mice.

    PubMed

    Enga, Rachel M; Jackson, Asti; Damaj, M Imad; Beardsley, Patrick M

    2016-10-15

    Abuse of prescription opioids, such as oxycodone, has markedly increased in recent decades. While oxycodone's antinociceptive effects have been detailed in several preclinical reports, surprisingly few preclinical reports have elaborated its abuse-related effects. This is particularly surprising given that oxycodone has been in clinical use since 1917. In a novel oral operant self-administration procedure, C57BL/6J mice were trained to self-administer water before introducing increasing concentrations of oxycodone (0.056-1.0mg/ml) under post-prandial conditions during daily, 3-h test sessions. As the concentration of oxycodone increased, the numbers of deliveries first increased, then decreased in an inverted U-shape fashion characteristic of the patterns of other drugs self-administered during limited access conditions. After post-prandial conditions were removed, self-administration at the highest concentration was maintained suggesting oral oxycodone served as a positive reinforcer. In other mice, using a novel regimen of physical dependence, mice were administered increasing doses of oxycodone (9.0-33.0mg/kg, s.c.) over 9 days, challenged with naloxone (0.1-10.0mg/kg, s.c.), and then observed for 30min. Naloxone dose-dependently increased the observed number of somatic signs of withdrawal, suggesting physical dependence of oxycodone was induced under this regimen. This is the first report demonstrating induction of oral operant self-administration of oxycodone and dose-dependent precipitations of oxycodone withdrawal in C57BL/6J mice. The use of oral operant self-administration as well as the novel physical dependence regimen provides useful approaches to further examine the abuse- and dependence-related effects of this highly abused prescription opioid. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Does oral health matter in people's daily life? Oral health-related quality of life in adults 35-47 years of age in Norway.

    PubMed

    Dahl, K E; Wang, N J; Ohrn, K

    2012-02-01

    The aim of this study was to assess the effect of oral health on aspects of daily life measured by the Dental Impact Profile (DIP) in 35- to 47-year-old individuals in Norway, and to study associations between reported effects and demographic variables, subjectively assessed oral health, general health, oral health behaviour and clinical oral health. A stratified randomized sample of 249 individuals received a questionnaire regarding demographic questions, dental visits, oral hygiene behaviour, self-rated oral health and general health and satisfaction with oral health. The DIP measured the effects of oral health on daily life. Teeth present and caries experience were registered by clinical examination. Bi- and multivariate analyses and factor analysis were used. Items most frequently reported to be positively or negatively influenced by oral health were chewing and biting, eating, smiling and laughing, feeling comfortable and appearance. Only 1% reported no effects of oral health. Individuals with fewer than two decayed teeth, individuals who rated their oral health as good or practised good oral health habits reported more positive effects than others on oral quality of life (P ≤ 0.05). When the variables were included in multivariate analysis, none was statistically significant. The subscales of the DIP were somewhat different from the originally suggested subscales. This study showed that most adults reported oral health to be important for masticatory functions and confirmed that oral health also had impacts on other aspects of life. © 2011 John Wiley & Sons A/S.

  7. Suppression of Gonadotropins and Estradiol in Premenopausal Women by Oral Administration of the Nonpeptide Gonadotropin-Releasing Hormone Antagonist Elagolix

    PubMed Central

    Struthers, R. Scott; Nicholls, Andrew J.; Grundy, John; Chen, Takung; Jimenez, Roland; Yen, Samuel S. C.; Bozigian, Haig P.

    2009-01-01

    Context: Parenteral administration of peptide GnRH analogs is widely employed for treatment of endometriosis and fibroids and in assisted-reproductive therapy protocols. Elagolix is a novel, orally available nonpeptide GnRH antagonist. Objective: Our objective was to evaluate the safety, pharmacokinetics, and inhibitory effects on gonadotropins and estradiol of single-dose and 7-d elagolix administration to healthy premenopausal women. Design: This was a first-in-human, double-blind, placebo-controlled, single- and multiple-dose study with sequential dose escalation. Participants: Fifty-five healthy, regularly cycling premenopausal women participated. Interventions: Subjects were administered a single oral dose of 25–400 mg or placebo. In a second arm of the study, subjects received placebo or 50, 100, or 200 mg once daily or 100 mg twice daily for 7 d. Treatment was initiated on d 7 (±1) after onset of menses. Main Outcome Measures: Safety, tolerability, pharmacokinetics, and serum LH, FSH, and estradiol concentrations were assessed. Results: Elagolix was well tolerated and rapidly bioavailable after oral administration. Serum gonadotropins declined rapidly. Estradiol was suppressed by 24 h in subjects receiving at least 50 mg/d. Daily (50–200 mg) or twice-daily (100 mg) administration for 7 d maintained low estradiol levels (17 ± 3 to 68 ± 46 pg/ml) in most subjects during late follicular phase. Effects of the compound were rapidly reversed after discontinuation. Conclusions: Oral administration of a nonpeptide GnRH antagonist, elagolix, suppressed the reproductive endocrine axis in healthy premenopausal women. These results suggest that elagolix may enable dose-related pituitary and gonadal suppression in premenopausal women as part of treatment strategies for reproductive hormone-dependent disease states. PMID:19033369

  8. Suppression of gonadotropins and estradiol in premenopausal women by oral administration of the nonpeptide gonadotropin-releasing hormone antagonist elagolix.

    PubMed

    Struthers, R Scott; Nicholls, Andrew J; Grundy, John; Chen, Takung; Jimenez, Roland; Yen, Samuel S C; Bozigian, Haig P

    2009-02-01

    Parenteral administration of peptide GnRH analogs is widely employed for treatment of endometriosis and fibroids and in assisted-reproductive therapy protocols. Elagolix is a novel, orally available nonpeptide GnRH antagonist. Our objective was to evaluate the safety, pharmacokinetics, and inhibitory effects on gonadotropins and estradiol of single-dose and 7-d elagolix administration to healthy premenopausal women. This was a first-in-human, double-blind, placebo-controlled, single- and multiple-dose study with sequential dose escalation. Fifty-five healthy, regularly cycling premenopausal women participated. Subjects were administered a single oral dose of 25-400 mg or placebo. In a second arm of the study, subjects received placebo or 50, 100, or 200 mg once daily or 100 mg twice daily for 7 d. Treatment was initiated on d 7 (+/-1) after onset of menses. Safety, tolerability, pharmacokinetics, and serum LH, FSH, and estradiol concentrations were assessed. Elagolix was well tolerated and rapidly bioavailable after oral administration. Serum gonadotropins declined rapidly. Estradiol was suppressed by 24 h in subjects receiving at least 50 mg/d. Daily (50-200 mg) or twice-daily (100 mg) administration for 7 d maintained low estradiol levels (17 +/- 3 to 68 +/- 46 pg/ml) in most subjects during late follicular phase. Effects of the compound were rapidly reversed after discontinuation. Oral administration of a nonpeptide GnRH antagonist, elagolix, suppressed the reproductive endocrine axis in healthy premenopausal women. These results suggest that elagolix may enable dose-related pituitary and gonadal suppression in premenopausal women as part of treatment strategies for reproductive hormone-dependent disease states.

  9. The effect of orally administered ranitidine and once-daily or twice-daily orally administered omeprazole on intragastric pH in cats.

    PubMed

    Šutalo, S; Ruetten, M; Hartnack, S; Reusch, C E; Kook, P H

    2015-01-01

    Gastric acid suppressants frequently are used in cats with acid-related gastric disorders. However, it is not known if these drugs effectively increase intragastric pH in cats. To examine the effects of PO administered ranitidine and omeprazole on intragastric pH in cats and to compare the efficacy of once-daily versus twice-daily dosage regimens for omeprazole. Eight domestic shorthair cats. Using a randomized 4-way cross-over design, cats were given enteric-coated omeprazole granules (1.1-1.3 mg/kg q24h and q12h), ranitidine (1.5-2.3 mg/kg q12h), and placebo. Intragastric pH was monitored continuously for 96 hours using the Bravo(™) system, starting on day 4 of treatment, followed by a median washout period of 12 days. Mean percentage of time pH was ≥3 and ≥4 was compared among groups using repeated measures ANOVA. Mean ± SD percentage of time intragastric pH was ≥3 and ≥4 was 67.0 ± 24.0% and 54.6 ± 26.4% for twice-daily omeprazole, 24.4 ± 22.8% and 16.8 ± 19.3% for once-daily omeprazole, 16.5 ± 9.0% and 9.6 ± 5.9% for ranitidine, and 9.4 ± 8.0% and 7.0 ± 6.6% for placebo administration. Twice-daily omeprazole treatment significantly increased intragastric pH, whereas pH after once-daily omeprazole and ranitidine treatments did not differ from that of placebo-treated cats. Only twice-daily PO administered omeprazole significantly suppressed gastric acidity in healthy cats, whereas once-daily omeprazole and standard dosages of ranitidine were not effective acid suppressants in cats. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

  10. Prevention of Infectious Mastitis by Oral Administration of Lactobacillus salivarius PS2 During Late Pregnancy.

    PubMed

    Fernández, Leónides; Cárdenas, Nivia; Arroyo, Rebeca; Manzano, Susana; Jiménez, Esther; Martín, Virginia; Rodríguez, Juan Miguel

    2016-03-01

    Previous studies have shown that oral administration of lactobacilli can be an efficient approach to treat lactational infectious mastitis. In this trial, we have evaluated the potential of Lactobacillus salivarius PS2 to prevent this condition when orally administered during late pregnancy to women who had experienced infectious mastitis after previous pregnancies. In this study, 108 pregnant women were randomly assigned to one of 2 groups. Those in the probiotic group (n = 55) ingested daily 9 log10 colony-forming units of L. salivarius PS2 from approximately week 30 of pregnancy until delivery, whereas those in the placebo group (n = 53) received a placebo. The occurrence of mastitis was evaluated during the first 3 months after delivery. Globally, 44 of 108 women (41%) developed mastitis; however, the percentage of women with mastitis in the probiotic group (25% [n = 14]) was significantly lower than in the control group (57% [n = 30]). When mastitis occurred, the milk bacterial counts in the probiotic group were significantly lower than those obtained in the placebo group. Oral administration of L. salivarius PS2 during late pregnancy appears to be an efficient method to prevent infectious mastitis in a susceptible population. NCT01505361. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  11. Neuroprotective effect of oral choline administration after global brain ischemia in rats.

    PubMed

    Borges, Andrea Aurélio; El-Batah, Philipe Nicolas; Yamashita, Lilia Fumie; Santana, Aline dos Santos; Lopes, Antonio Carlos; Freymuller-Haapalainen, Edna; Coimbra, Cicero Galli; Sinigaglia-Coimbra, Rita

    2015-08-01

    Choline - now recognized as an essential nutrient - is the most common polar group found in the outer leaflet of the plasma membrane bilayer. Brain ischemia-reperfusion causes lipid peroxidation triggering multiple cell death pathways involving necrosis and apoptosis. Membrane breakdown is, therefore, a major pathophysiologic event in brain ischemia. The ability to achieve membrane repair is a critical step for survival of ischemic neurons following reperfusion injury. The availability of choline is a rate-limiting factor in phospholipid synthesis and, therefore, may be important for timely membrane repair and cell survival. This work aimed at verifying the effects of 7-day oral administration with different doses of choline on survival of CA1 hippocampal neurons following transient global forebrain ischemia in rats. The administration of 400 mg/kg/day divided into two daily doses for 7 consecutive days significantly improved CA1 pyramidal cell survival, indicating that the local availability of this essential nutrient may limit postischemic neuronal survival.

  12. Effects of daily delta-9-tetrahydrocannabinol treatment on heroin self-administration in rhesus monkeys

    PubMed Central

    Maguire, David R.; France, Charles P.

    2015-01-01

    Opioid abuse remains a significant public health problem; together with the greater availability of marijuana in some regions there is an increasing likelihood that opioids and marijuana will be used together. Poly-drug abuse is associated with increased toxicity and poorer treatment outcome; thus, a better understanding of the consequences of repeated co-administration of these drugs will facilitate the development of better prevention and treatment strategies. This study examined the effects of daily treatment with the cannabinoid receptor agonist delta-9-tetrahydrocannabinol (Δ9-THC) and its discontinuation on self-administration of heroin in rhesus monkeys (n=4) lever-pressing under a fixed-ratio 30 schedule. Heroin self-administration (0.32–32 μg/kg/infusion, i.v.) generated an inverted U-shaped dose–effect curve. Administered acutely, Δ9-THC (0.01–0.32 mg/kg, s.c.) dose dependently decreased responding for heroin and flattened the self-administration dose-effect curve. Daily treatment with Δ9-THC (0.01–0.1 mg/kg/12hr, s.c.) either had no effect on or decreased responding for heroin. In addition, daily treatment did not significantly impact extinction of heroin self-administration or resumption of responding for heroin after extinction. Discontinuation of daily Δ9-THC treatment did not systematically impact rates of heroin self-administration. These data suggest that repeated administration of a cannabinoid receptor agonist likely does not increase, and possibly decreases, the positive reinforcing effects of a mu opioid receptor agonist. PMID:26397756

  13. Effects of daily delta-9-tetrahydrocannabinol treatment on heroin self-administration in rhesus monkeys.

    PubMed

    Maguire, David R; France, Charles P

    2016-04-01

    Opioid abuse remains a significant public health problem; together with the greater availability of marijuana in some regions there is an increasing likelihood that opioids and marijuana will be used together. Polydrug abuse is associated with increased toxicity and poorer treatment outcome; thus, a better understanding of the consequences of repeated coadministration of these drugs will facilitate the development of better prevention and treatment strategies. This study examined the effects of daily treatment with the cannabinoid receptor agonist delta-9-tetrahydrocannabinol (Δ-THC) and its discontinuation on self-administration of heroin in rhesus monkeys (n=4) lever-pressing under a fixed-ratio 30 schedule. Heroin self-administration (0.32-32 μg/kg/infusion, intravenously) generated an inverted U-shaped dose-effect curve. Administered acutely, Δ-THC (0.01-0.32 mg/kg, subcutaneously) dose dependently decreased responding for heroin and flattened the self-administration dose-effect curve. Daily treatment with Δ-THC (0.01-0.1 mg/kg/12 h, subcutaneously) either had no effect on or decreased responding for heroin. In addition, daily treatment did not significantly impact extinction of heroin self-administration or resumption of responding for heroin after extinction. Discontinuation of daily Δ-THC treatment did not systematically impact rates of heroin self-administration. These data suggest that repeated administration of a cannabinoid receptor agonist likely does not increase, and possibly decreases, the positive reinforcing effects of a mu opioid receptor agonist.

  14. Oral administration of paraquat perturbs immunoglobulin productivity in mouse.

    PubMed

    Okabe, Masaaki; Nishimoto, Sogo; Sugahara, Takuya; Akiyama, Koichi; Kakinuma, Yoshimi

    2010-04-01

    Paraquat is one of the most widely used herbicides in the world and has been known to injure lungs, liver and skin in animals and human. Hence, it is important to understand the manner of paraquat in mammals. We studied the effect of paraquat on the immune function of mouse in vitro and in vivo. When splenocytes were cultured in vitro with various concentrations of paraquat, IgA productivity was not affected while IgG and IgM productivity decreased. On the other hand, Oral administration of paraquat for 1, 2 or 3 weeks increased IgA level but decreased IgM levels in serum of mice. Similarly IgA productivity increased while IgM productivity decreased. These results suggest that paraquat perturbs the lymphocytes immunoglobulin productivity in an immunoglobulin class-dependent manner.

  15. Creatine metabolism and safety profiles after six-week oral guanidinoacetic acid administration in healthy humans.

    PubMed

    Ostojic, Sergej M; Niess, Barbara; Stojanovic, Marko; Obrenovic, Milos

    2013-01-01

    Guanidinoacetic acid (GAA) is a natural precursor of creatine, yet the potential use of GAA as a nutritional additive for restoring creatine availability in humans has been limited by unclear efficacy and safety after exogenous GAA administration. The present study evaluated the effects of orally administered GAA on serum and urinary GAA, creatine and creatinine concentration, and on the occurrence of adverse events in healthy humans. Twenty-four healthy volunteers were randomized in a double-blind design to receive either GAA (2.4 grams daily) or placebo (PLA) by oral administration for 6 weeks. www.clinicaltrials.gov, identification number NCT01133899. Serum creatine and creatinine increased significantly from before to after administration in GAA-supplemented participants (P < 0.05). The proportion of participants who reported minor side effects was 58.3% in the GAA group and 45.5% in the placebo group (P = 0.68). A few participants experienced serum creatine levels above 70 µmol/L. Exogenous GAA is metabolized to creatine, resulting in a significant increase of fasting serum creatine after intervention. GAA had an acceptable side-effects profile with a low incidence of biochemical abnormalities.

  16. Creatine Metabolism and Safety Profiles after Six-Week Oral Guanidinoacetic Acid Administration in Healthy Humans

    PubMed Central

    Ostojic, Sergej M.; Niess, Barbara; Stojanovic, Marko; Obrenovic, Milos

    2013-01-01

    Objectives; Guanidinoacetic acid (GAA) is a natural precursor of creatine, yet the potential use of GAA as a nutritional additive for restoring creatine availability in humans has been limited by unclear efficacy and safety after exogenous GAA administration. The present study evaluated the effects of orally administered GAA on serum and urinary GAA, creatine and creatinine concentration, and on the occurrence of adverse events in healthy humans. Methods and Results; Twenty-four healthy volunteers were randomized in a double-blind design to receive either GAA (2.4 grams daily) or placebo (PLA) by oral administration for 6 weeks. Clinical trial registration: www.clinicaltrials.gov, identification number NCT01133899. Serum creatine and creatinine increased significantly from before to after administration in GAA-supplemented participants (P < 0.05). The proportion of participants who reported minor side effects was 58.3% in the GAA group and 45.5% in the placebo group (P = 0.68). A few participants experienced serum creatine levels above 70 µmol/L. Conclusion; Exogenous GAA is metabolized to creatine, resulting in a significant increase of fasting serum creatine after intervention. GAA had an acceptable side-effects profile with a low incidence of biochemical abnormalities. PMID:23329885

  17. Prolonged neurophysiologic effects of levetiracetam after oral administration in humans.

    PubMed

    Epstein, Charles M; Girard-Siqueira, Lhys; Ehrenberg, Joshua Andrew

    2008-07-01

    To determine whether neurophysiological effects of levetiracetam (LEV) outlast its serum half-life of approximately 7 h. Demonstration of prolonged effects would help to explain the efficacy of LEV at conventional dosing intervals that are longer than the serum half-life. Following an oral dose of LEV 3 g in 12 normal volunteers, we compared transcranial magnetic stimulation (TMS) measures of motor threshold (MT) and recruitment with LEV serum levels and subjective ratings of toxicity over 48 h. Subjects used a two-dimensional visual-analog scale to estimate the time course of any side effects. LEV serum levels and subjective toxicity both peaked around 1 h after oral administration. MT elevation was delayed in comparison to peak serum levels and subjective toxicity. MT was maximally elevated at 6-9 h, and recruitment maximally reduced at 0.6-9 h. Changes in both measures had recovered by approximately 50% at 24 h. Despite the time difference between toxicity and TMS changes, toxicity estimates correlated with the maximum increase in MT. There is a substantial time lag between LEV serum levels and TMS measures of neuronal effects, and a similar temporal dissociation between subjective toxicity and maximum TMS change. The time course of neurophysiological effects, as measured by TMS, may help to explain the sustained clinical efficacy of LEV despite a short peripheral half-life.

  18. Teriflunomide: a once-daily oral medication for the treatment of relapsing forms of multiple sclerosis.

    PubMed

    Miller, Aaron E

    2015-10-01

    The purpose was to summarize US prescribing information for teriflunomide in the treatment of patients with relapsing forms of multiple sclerosis (RMS), with reference to clinical efficacy and safety outcomes. In September 2012, the US Food and Drug Administration granted approval for the use of teriflunomide, 14 mg and 7 mg once daily, to treat RMS on the basis of the results of a Phase II study and the Phase III TEMSO (Teriflunomide Multiple Sclerosis Oral) trial. After recent updates to the prescribing information (October 2014), key findings from these and 2 other Phase III clinical trials, TOWER (Teriflunomide Oral in People With Relapsing Multiple Sclerosis) and TOPIC (Oral Teriflunomide for Patients with a First Clinical Episode Suggestive of Multiple Sclerosis), and practical considerations for physicians are summarized. Teriflunomide, 14 mg and 7 mg, significantly reduced mean number of unique active lesions on magnetic resonance imaging (MRI; P < 0.05 for both doses) in the Phase II study. In the TEMSO and TOWER studies, the 14-mg dose of teriflunomide significantly reduced annualized relapse rate (31% and 36% relative risk reduction compared with placebo, respectively; both P < 0.001) and risk of disability progression sustained for 12 weeks (hazard ratio vs placebo 0.70 and 0.69, respectively; both P < 0.05). The 7-mg dose significantly (P < 0.02) reduced annualized relapse rate in both studies, although the reduction in risk of disability progression was not statistically significant. Teriflunomide treatment was also associated with significant efficacy on MRI measures of disease activity in TEMSO; both doses significantly reduced total lesion volume and number of gadolinium-enhancing T1 lesions. TOPIC evaluated patients with a first clinical event consistent with acute demyelination and brain MRI lesions characteristic of multiple sclerosis. More patients were free of relapse in the teriflunomide 14-mg and 7-mg groups than in the placebo group (P

  19. Two cases of corneal perforation after oral administration of nonsteroidal anti-inflammatory drugs: oral NSAID-induced corneal damage.

    PubMed

    Masuda, Ikuya; Matsuo, Toshihiko; Okamoto, Kazuo; Matsushita, Kyoko; Ohtsuki, Hiroshi

    2010-01-01

    To report 2 cases of corneal perforation associated with the use of oral nonsteroidal anti-inflammatory drugs (NSAIDs). In a 62-year-old woman and a 79-year-old woman, corneal perforation occurred after 7 days and 5 months of oral NSAIDs administration, respectively. After NSAIDs were discontinued, the cornea epithelialized and the anterior chamber formed within 14 and 10 days, respectively. It is well known that topical NSAIDs cause corneal perforation. Observations in the present cases suggest that the oral administration of NSAIDs may also cause corneal damage, and hence, medical professionals should consider the risk of damage to the cornea when administering these drugs orally.

  20. Testing reliability and validity of oral impacts on daily performances for Chinese-speaking elderly Singaporeans.

    PubMed

    Nair, Rahul; Tsakos, Georgios; Yee Ting Fai, Robert

    2016-12-01

    To cross-culturally adapt the oral impacts on daily performance (OIDP) and assess its reliability and validity on Chinese-speaking community dwelling elderly Singaporeans. There are no previous reports of valid oral health-related quality of life instruments for elderly Singaporeans or perceived conditions associated with impacts reported in OIDP among the Singaporean elders. The OIDP was translated from English to Chinese and then back translated. The OIDP questionnaire along with questions related to overall quality of life and self-rated dental health was administered to 202 Chinese-speaking elderly Singaporeans by trained interviewers, and it was repeated after 1 month. Test-retest reliability was assessed using intraclass correlation coefficient; internal consistency was established using Cronbach's alpha, and construct validity using correlation coefficients with self-reported oral health-related and global quality of life measures. In addition, Kruskal-Wallis tests assessed differences in the OIDP score between different subjective health and global quality of life groups. The median age of participants was 75 years. About 19% reported oral impacts and difficulty eating was the most prevalent oral impact. Internal consistency was good with a Cronbach's alpha of 0.75, and the intraclass correlation coefficient was 0.75 (0.67-0.81). OIDP was significantly correlated with all measures of self-reported oral health and global ratings of quality of life, with correlation coefficients ranging between 0.15 and 0.52. Groups with worse perceptions about their health and quality of life had significantly higher OIDP scores. The OIDP showed successful reliability and validity for its use among Chinese-speaking older Singaporeans. © 2015 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

  1. Thermal antinociception after dexmedetomidine administration in cats: a comparison between intramuscular and oral transmucosal administration.

    PubMed

    Slingsby, Louisa S; Taylor, Polly M; Monroe, Taylor

    2009-10-01

    Dexmedetomidine 40microg/kg was administered either intramuscularly (IM) or oral transmucosally (OTM) to 12 cats in a randomised cross-over study. Thermal nociceptive thresholds and visual analogue scale (VAS) sedation scores were obtained before and at regular intervals up to 24h after test drug administration. The summary measures of overall mean threshold, overall mean VAS sedation plus onset, offset and duration of analgesia were investigated using a univariate general linear model. There were no significant differences between treatment groups. Data are presented as mean+/-standard deviation: delta T mean increase over time (IM 6 degrees C+/-3 degrees C, OTM 6 degrees C+/-2 degrees C); overall mean VAS (IM 43+/-9 OTM 39+/-1); onset (IM 35+/-32 and OTM 30+/-40min); offset (IM 96+/-56 and OTM 138+/-135min); duration (IM 61+/-47 OTM 99+/-124min). Dexmedetomidine is well absorbed through the oral mucosa in cats since OTM and IM administration of dexmedetomidine 40microg/kg produced similar overall sedative and antinociceptive effects.

  2. Mitigating effects of vaccination on influenza outbreaks given constraints in stockpile size and daily administration capacity

    PubMed Central

    2011-01-01

    Background Influenza viruses are a major cause of morbidity and mortality worldwide. Vaccination remains a powerful tool for preventing or mitigating influenza outbreaks. Yet, vaccine supplies and daily administration capacities are limited, even in developed countries. Understanding how such constraints can alter the mitigating effects of vaccination is a crucial part of influenza preparedness plans. Mathematical models provide tools for government and medical officials to assess the impact of different vaccination strategies and plan accordingly. However, many existing models of vaccination employ several questionable assumptions, including a rate of vaccination proportional to the population at each point in time. Methods We present a SIR-like model that explicitly takes into account vaccine supply and the number of vaccines administered per day and places data-informed limits on these parameters. We refer to this as the non-proportional model of vaccination and compare it to the proportional scheme typically found in the literature. Results The proportional and non-proportional models behave similarly for a few different vaccination scenarios. However, there are parameter regimes involving the vaccination campaign duration and daily supply limit for which the non-proportional model predicts smaller epidemics that peak later, but may last longer, than those of the proportional model. We also use the non-proportional model to predict the mitigating effects of variably timed vaccination campaigns for different levels of vaccination coverage, using specific constraints on daily administration capacity. Conclusions The non-proportional model of vaccination is a theoretical improvement that provides more accurate predictions of the mitigating effects of vaccination on influenza outbreaks than the proportional model. In addition, parameters such as vaccine supply and daily administration limit can be easily adjusted to simulate conditions in developed and developing

  3. Effect of oral administration of carprofen on intraocular pressure in normal dogs.

    PubMed

    Meekins, J M; Overton, T L; Rankin, A J; Roush, J K

    2016-08-01

    The aim of this study was to determine the effect of oral administration of carprofen on intraocular pressure in normal dogs. Twelve young adult beagle dogs were randomly assigned to treatment (n = 6) or control (n = 6) groups. After an 11-day acclimation period, the treatment group received approximately 2.2 mg/kg carprofen per os every 12 h for 7 days, and the control group received a placebo gel capsule containing no drug per os every 12 h for 7 days. Intraocular pressure (IOP) was measured by a rebound tonometer at three time points per day (8 am, 2 pm, and 8 pm) during the acclimation (days 1-11) and treatment (days 12-18) phases and for 48 h (days 19-20) after the completion of treatment. There was no statistically significant change in IOP for either eye in the dogs receiving oral carprofen during the treatment phase (days 12-18). After day 4, no significant daily IOP changes were seen in control group dogs. Carprofen administered orally every 12 h for 7 days had no effect on IOP in normal beagle dogs. An acclimation period to frequent IOP measurements of at least 5 days is necessary to establish baseline IOP values and minimize possible anxiety-related effects on IOP measurements. © 2016 John Wiley & Sons Ltd.

  4. Treatment of Hypertension: Favourable Effect of the Twice-Daily Compared to the Once-Daily (Evening) Administration of Perindopril and Losartan.

    PubMed

    Szauder, Ipoly; Csajági, Eszter; Major, Zsuzsanna; Pavlik, Gabor; Ujhelyi, Gabriella

    2015-01-01

    Little is known about the effect of twice daily administration of same dose of ACE inhibitor and ARB on the diurnal/nocturnal blood pressure (BP) ratio. We aimed to assess the effect of two widely used long-acting drugs: perindopril and losartan in the treatment of hypertension comparing the once-daily (evening) vs. twice-daily (morning and evening) administration with the same daily doses. Untreated primary hypertensive patients without complaints (a total of 164: 65 men, 99 women, 55.7 ± 13.7 years of age, 41-41 patients per treated groups) were selected with non-dipper phenomenon, estimated by diurnal index (DI) <10%. The effect of evening (8 mg perindopril or 100 mg losartan) vs morning and evening (4-4 mg perindopril or 50-50 mg losartan) administration was determined on a 14-day treatment by ABPM. The mean BP, the percent time elevation index, and the hyperbaric impact decreased in both drug groups. Significant difference was observed in the DI in the case of twice-daily administration vs once-daily evening dosing. The twice-daily administration with the same daily dose of perindopril or losartan seems to be more effective compared to the once daily evening administration in eliminating the non-dipper phenomenon. According to some authors the non-dipping phenomenon increases cardiovascular risk, while others are of the opinion that the association of non-dipping with cardiovascular events does not necessarily mean that selective treatment of non-dipping improves cardiovascular outcomes. © 2015 S. Karger AG, Basel.

  5. Oral administration of quercetin is unable to protect against isoproterenol cardiotoxicity.

    PubMed

    Ríha, Michal; Vopršalová, Marie; Pilařová, Veronika; Semecký, Vladimír; Holečková, Magdalena; Vávrová, Jaroslava; Palicka, Vladimir; Filipský, Tomáš; Hrdina, Radomír; Nováková, Lucie; Mladěnka, Přemysl

    2014-09-01

    Catecholamines are endogenous amines that participate in the maintenance of cardiovascular system homeostasis. However, excessive release or exogenous administration of catecholamines is cardiotoxic. The synthetic catecholamine, isoprenaline (isoproterenol, ISO), with non-selective β-agonistic activity has been used as a viable model of acute myocardial toxicity for many years. Since the pathophysiology of ISO-cardiotoxicity is complex, the aim of this study was to elucidate the effect of oral quercetin pretreatment on myocardial ISO toxicity. Wistar-Han rats were randomly divided into four groups: solvent or quercetin administered orally by gavage in a dose of 10 mg kg(-1) daily for 7 days were followed by s.c. water for injection or ISO in a dose of 100 mg kg(-1). Haemodynamic, ECG and biochemical parameters were measured; effects on blood vessels and myocardial histology were assessed, and accompanying pharmacokinetic analysis was performed. Quercetin was unable to protect the cardiovascular system against acute ISO cardiotoxicity (stroke volume decrease, cardiac troponin T release, QRS-T junction elevation and histological impairment). The sole positive effect of quercetin on catecholamine-induced cardiotoxicity was the normalization of increased left ventricular end-diastolic pressure caused by ISO. Quercetin did not reverse the increased responsiveness of rat aorta to vasoconstriction in ISO-treated animals, but it decreased the same parameter in the control animals. Accompanying pharmacokinetic analysis showed absorption of quercetin and its metabolite 3-hydroxyphenylacetic acid formed by bacterial microflora. In conclusion, a daily oral dose of 10 mg kg(-1) of quercetin for 7 days did not ameliorate acute ISO-cardiovascular toxicity in rats despite minor positive cardiovascular effects.

  6. Randomized clinical trial to comparing efficacy of daily, weekly and monthly administration of vitamin D3.

    PubMed

    Takács, István; Tóth, Béla E; Szekeres, László; Szabó, Boglárka; Bakos, Bence; Lakatos, Péter

    2017-01-01

    The comparative efficacy and safety profiles of selected daily 1000 IU, weekly 7000 IU and monthly 30,000 IU vitamin D 3 -not previously investigated-will be evaluated. Here, a prospective, randomized clinical trial, comparing efficacy and safety of a daily single dose of 1000 IU (group A) to a once-weekly 7000 IU dose (group B), or monthly 30,000 IU dose (group C) of vitamin D 3 . The present study is a controlled, randomized, open-label, multicenter clinical trial, 3  months in duration. Sixty-four adult subjects with vitamin D deficiency (25OHD<20 ng/ml), were included according to the inclusion and exclusion criteria. Dose-responses for increases in serum vitamin 25OHD were statistically equivalent for each of the three groups: A, B and C. Outcomes were 13.0 ± 1.5; 12.6 ± 1.1 and 12.9 ± 0.9 ng/ml increases in serum 25OHD per 1000 IU, daily, weekly and monthly, respectively. The treatment of subjects with selected doses restored 25OHD values to levels above 20 ng/ml in all groups. Treatment with distinct administration frequency of vitamin D 3 did not exhibit any differences in safety parameters. The daily, weekly and monthly administrations of daily equivalent of 1000 IU of vitamin D 3 provide equal efficacy and safety profiles.

  7. Pharmacokinetics of Memantine after a Single and Multiple Dose of Oral and Patch Administration in Rats.

    PubMed

    Lee, Soo-Han; Kim, Seung-Hyun; Noh, Yook-Hwan; Choi, Byung-Moon; Noh, Gyu-Jeong; Park, Woo-Dae; Kim, Eun-Jung; Cho, Ik-Hyun; Bae, Chun-Sik

    2016-02-01

    Memantine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist used to treat Alzheimer's disease. We investigated memantine pharmacokinetics after oral, IV and patch administration in rats, and compared memantine pharmacokinetics after multiple- or single-dose oral and transdermal administration. Venous blood was collected at preset intervals in single- and multiple-dose studies. Non-compartmental pharmacokinetics was analysed for all formulations. The oral, IV and patch memantine doses were 10 mg/kg, 2 mg/kg and 8.21 ± 0.89 mg/kg, respectively. The maximum plasma concentration was lower and the half-life longer after patch administration than oral and IV administration. Memantine bioavailability was 41 and 63% for oral and patch administration, respectively. Steady state was achieved around 24 hr for oral and patch administration. The mean AUC increased after oral or patch administration from single to multiple dose. The memantine patch formulation displayed a longer duration of action and lower peak plasma concentration. However, drug exposure was similar to the oral formulation at each dose. Additionally, the memantine patch formulation displayed a smaller interindividual variability and lower accumulation than the oral formulation. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  8. Administrative Challenges to the Integration of Oral Health With Primary Care

    PubMed Central

    Maxey, Hannah L.; Randolph, Courtney; Gano, Laura; Kochhar, Komal

    2017-01-01

    Inadequate access to preventive oral health services contributes to oral health disparities and is a major public health concern in the United States. Federally Qualified Health Centers play a critical role in improving access to care for populations affected by oral health disparities but face a number of administrative challenges associated with implementation of oral health integration models. We conducted a SWOT (strengths, weaknesses, opportunities, and threats) analysis with health care executives to identify strengths, weaknesses, opportunities, and threats of successful oral health integration in Federally Qualified Health Centers. Four themes were identified: (1) culture of health care organizations; (2) operations and administration; (3) finance; and (4) workforce. PMID:27218701

  9. Pharmacokinetics of repeated oral administration of tramadol hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis).

    PubMed

    Souza, Marcy J; Gerhardt, Lillian; Cox, Sherry

    2013-07-01

    To determine the pharmacokinetics of tramadol hydrochloride (30 mg/kg) following twice-daily oral administration in Hispaniolan Amazon parrots (Amazona ventralis). 9 healthy adult Hispaniolan Amazon parrots. Tramadol hydrochloride was administered to each parrot at a dosage of 30 mg/kg, PO, every 12 hours for 5 days. Blood samples were collected just prior to dose 2 on the first day of administration (day 1) and 5 minutes before and 10, 20, 30, 60, 90, 180, 360, and 720 minutes after the morning dose was given on day 5. Plasma was harvested from blood samples and analyzed by high-performance liquid chromatography. Degree of sedation was evaluated in each parrot throughout the study. No changes in the parrots' behavior were observed. Twelve hours after the first dose was administered, mean ± SD concentrations of tramadol and its only active metabolite M1 (O-desmethyltramadol) were 53 ± 57 ng/mL and 6 ± 6 ng/mL, respectively. At steady state following 4.5 days of twice-daily administration, the mean half-lives for plasma tramadol and M1 concentrations were 2.92 ± 0.78 hours and 2.14 ± 0.07 hours, respectively. On day 5 of tramadol administration, plasma concentrations remained in the therapeutic range for approximately 6 hours. Other tramadol metabolites (M2, M4, and M5) were also present. On the basis of these results and modeling of the data, tramadol at a dosage of 30 mg/kg, PO, will likely need to be administered every 6 to 8 hours to maintain therapeutic plasma concentrations in Hispaniolan Amazon parrots.

  10. Long-term experience with deferasirox (ICL670), a once-daily oral iron chelator, in the treatment of transfusional iron overload.

    PubMed

    Cappellini, M D; Taher, A

    2008-09-01

    Chronic iron overload from frequent blood transfusions to treat patients with severe anaemias leads to significant morbidity and mortality. While deferoxamine, the current standard of care, is an effective iron chelator, it requires subcutaneous infusion for 8-12 h/day, 5-7 days/week. This regimen is problematic and impacts significantly on patients' daily life. To evaluate the efficacy and tolerability of deferasirox, a once-daily oral iron chelator. To review the available data reported in peer-reviewed journals (using PubMed) and at medical conferences. Deferasirox is effective in reducing or maintaining iron burden in patients with transfusion-dependent anaemias. As deferasirox is orally administered, the inconvenience of parenteral administration with deferasirox is avoided. Deferasirox improves patient satisfaction and is expected to improve compliance with iron chelation therapy.

  11. Attenuation of cocaine self-administration by chronic oral phendimetrazine in rhesus monkeys.

    PubMed

    Czoty, P W; Blough, B E; Fennell, T R; Snyder, R W; Nader, M A

    2016-06-02

    Chronic treatment with the monoamine releaser d-amphetamine has been consistently shown to decrease cocaine self-administration in laboratory studies and clinical trials. However, the abuse potential of d-amphetamine is an obstacle to widespread clinical use. Approaches are needed that exploit the efficacy of the agonist approach but avoid the abuse potential associated with dopamine releasers. The present study assessed the effectiveness of chronic oral administration of phendimetrazine (PDM), a pro-drug for the monoamine releaser phenmetrazine (PM), to decrease cocaine self-administration in four rhesus monkeys. Each day, monkeys pressed a lever to receive food pellets under a 50-response fixed-ratio (FR) schedule of reinforcement and self-administered cocaine (0.003-0.56 mg/kg per injection, i.v.) under a progressive-ratio (PR) schedule in the evening. After completing a cocaine self-administration dose-response curve, sessions were suspended and PDM was administered (1.0-9.0 mg/kg, p.o., b.i.d.). Cocaine self-administration was assessed using the PR schedule once every 7 days while food-maintained responding was studied daily. When a persistent decrease in self-administration was observed, the cocaine dose-effect curve was re-determined. Daily PDM treatment decreased cocaine self-administration by 30-90% across monkeys for at least 4 weeks. In two monkeys, effects were completely selective for cocaine. Tolerance developed to initial decreases in food-maintained responding in the third monkey and in the fourth subject, fluctuations were observed that were lower in magnitude than effects on cocaine self-administration. Cocaine dose-effect curves were shifted down and/or rightward in three monkeys. These data provide further support for the use of agonist medications for cocaine abuse, and indicate that the promising effects of d-amphetamine extend to a more clinically viable pharmacotherapy. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Interaction of titanium dioxide nanoparticles with glucose on young rats after oral administration.

    PubMed

    Chen, Zhangjian; Wang, Yun; Zhuo, Lin; Chen, Shi; Zhao, Lin; Chen, Tian; Li, Yang; Zhang, Wenxiao; Gao, Xin; Li, Ping; Wang, Haifang; Jia, Guang

    2015-10-01

    Titanium dioxide nanoparticles (TiO2 NPs) have a broad application prospect in replace with TiO2 used as a food additive, especially used in sweets. Understanding the interaction of TiO2 NPs with sugar is meaningful for health promotion. We used a young animal model to study the toxicological effect of orally administrated TiO2 NPs at doses of 0, 2, 10 and 50 mg/kg per day with or without daily consumption of 1.8 g/kg glucose for 30 days and 90 days. The results showed that oral exposure to TiO2 NPs and TiO2 NPs+glucose both induced liver, kidney, and heart injuries as well as changes in the count of white and red blood cells in a dose, time and gender-dependent manner. The toxicological interactions between orally-administrated TiO2 NPs and glucose were evident, but differed among target organs. These results suggest that it is necessary to limit dietary co-exposure to TiO2 NPs and sugar. Nanotechnology has gained entrance in the food industry, with the presence of nanoparticles now in many food items. Despite this increasing trend, the potential toxic effects of these nanoparticles to human remain unknown. In this article, the authors studied titanium dioxide nanoparticles (TiO2 NPs), which are commonly used as food additive, together with glucose. The findings of possible adverse effects on liver, kidney, and heart might point to a rethink of using glucose and TiO2 NPs combination. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. [The effect of daily controlled oral hygiene on the oral health of children in a town with drinking water fluoridation (Karl Marx Stadt)].

    PubMed

    Georgi, J; Künzel, W

    1976-03-01

    Under the conditions of an optimized (with regard to caries prevention) fluoride content of the drinking uater, the authors studied (in the framework of an oral hygiene measure covering 32 months) in 149 children 6.5-8 years of age the effects of supervised daily dental and oral care on dental health. The improvement in oral hygiene (OHI) by 33% is in harmony with an additional caries reduction by 33.3% (DMF/S index) and a decrease of the PM index by 47%. A wider use of oral hygiene actions as secondary preventive measures is, therefore, recommended also for towns with fluoridated drinking water.

  14. The impact of oral health on daily performances and its association with clinical variables in a population in Zambia.

    PubMed

    Andersson, P; Kavakure, J; Lingström, P

    2017-05-01

    The aim of this study was to investigate oral impacts on daily performance and to relate these data to oral clinical variables. The study was performed at a dental clinic in Livingstone, Zambia, and included 78 subjects (mean age 28, range 15-48 years) consecutively recruited in connection with a dental care visit. Data were collected through a structured interview using the Oral Impacts on Daily Performances (OIDP) index measuring oral health-related quality of life followed by a clinical examination. Oral health affected one or more daily performances during the last 6 months for 61.5% of the subjects. 'Difficulty of eating and enjoying food' was the performance reported most frequently (42.3%), and 'speaking and pronouncing clearly' was least often reported (10.3%). DMFT was 3.8, ±3.6 (mean ± SD; range 0-15). A majority of the individuals had periodontal pockets ≥4 mm (mean 4.3, ±2.6) (94.9%) and gingival bleeding on probing >20% (88.5%). Two or more decayed teeth were shown to be significantly associated (OR 4.6, CI 1.2-17.1) with one or more oral impacts on daily performances in a multivariate logistic regression analysis. This study shown that there is a significant association between decayed teeth and oral impacts on daily performances. More research is needed, however, for deeper understanding of oral health problems and their impacts on daily life in Zambia. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Feasibility study of the use of a daily electronic mail reminder to improve oral contraceptive compliance.

    PubMed

    Fox, Michelle C; Creinin, Mitchell D; Murthy, Amitasrigowri S; Harwood, Bryna; Reid, Lynn M

    2003-11-01

    Women who ingest their oral contraceptive pill (OCP) as part of a daily routine are more likely use their OCPs correctly. This trial examines the feasibility of an electronic-mail (e-mail) reminder system to improve OCP compliance. An e-mail reminder was sent to 50 new OCP users daily for 3 months. Subjects sent an e-mail reply to confirm receipt. OCP compliance was recorded on diaries. Four subjects were discontinued for not checking their e-mail. Active participants missed a median of 18% of the e-mail reminders (range: 0-65%). A follow-up visit was scheduled after completion of three OCP cycles. Of the 40 subjects returning completed diaries, 50% missed no active pills at all and 20% missed at least one in each cycle. Most found the daily e-mail somewhat (65%) or very helpful (19%) for OCP compliance. Of those continuing OCPs, 64% wanted to continue receiving e-mail reminders at the completion of the study. Because inconsistent OCP use is a significant cause of unplanned conception, the use of e-mail to improve OCP compliance has the potential to decrease unintended pregnancies.

  16. Multiple oral dosing of ketoconazole influences pharmacokinetics of quinidine after intravenous and oral administration in beagle dogs.

    PubMed

    Kuroha, M; Shirai, Y; Shimoda, M

    2004-10-01

    In this study, we investigated the effect of multiple oral dosing of ketoconazole (KTZ) on pharmacokinetics of quinidine (QN), a CYP3A substrate with low hepatic clearance, after i.v. and oral administration in beagle dogs. Four dogs were given p.o. KTZ for 20 days (200 mg, b.i.d.). QN was administered either i.v. (1 mg/kg) or p.o. (100 mg) 10 and 20 days before the KTZ treatment and 10 and 20 days after start of KTZ treatment. Multiple oral dosing of KTZ decreased significantly alpha and beta, whereas increased t(1/2beta), V(1), and k(a). The KTZ treatment also decreased significantly both total body clearance (Cl(tot)) and oral clearance (Cl(oral)). No significant change in bioavailability was observed in the presence of KTZ. Co-administration of KTZ increased C(max) of QN to about 1.5-fold. Mean resident time after i.v. administration (MRT(i.v.)), and after oral administration (MRT(p.o.)) of QN were prolonged to about twofold, whereas mean absorption time (MAT) was decreased to 50%. Volume of distribution at steady state (V(d(ss))) of QN was unchanged in the presence of KTZ. These alterations may be because of a decrease in metabolism of QN by inhibition of KTZ on hepatic CYP3A activity. In conclusion, multiple oral dosing of KTZ affected largely pharmacokinetics of QN after i.v. and oral administration in beagle dogs. Therefore, KTZ at a clinical dosing regimen may markedly change the pharmacokinetics of drugs primarily metabolized by CYP3A with low hepatic clearance in dogs. In clinical use, much attention should be paid to concomitant administration of KTZ with the drug when given either p.o. or i.v.

  17. [Intermediary effectiveness of procaine and procaine metabolites following oral administration].

    PubMed

    Kaemmerer, K; Kietzmann, M

    1989-01-01

    The influence of orally administrated procaine hydrochloride and of its metabolites diethylaminoethanol, monoethylaminoethanol and ethanolamine on specific intermediary processes in rats was tested. While the animals got procaine hydrochloride in a single dose or via food the incorporation rate of amino acids in protein was measured in homogenisates of liver tissue by the incorporation of a mixture of 14C-amino acids. Procaine hydrochloride, the commercial product K. H. 3, as well as diethylaminoethanol, monoethylaminoethanol and ethanolamine increased the amino acid incorporation rate in a dose and time dependent mode, while p-aminobenzoic acid remained without any effect. The dose of procaine hydrochloride inducing a maximal reaction was in the range of 50 to 100 mg/kg b. w. (250 to 500 mg/kg food). The minimal active dose was nearly at 10 mg/kg b. w. Paying regard to a metabolic factor of 10 the effective dose-range is nearly the dose used in experience with human beings to influence geriatric complaints. In the study described here haematoporphyrine (a component of the commercial product K. H. 3, not absorbed) shows no specific intermediary effect. May be it promotes the intestinal absorption of procaine hydrochloride by protection against intestinal hydrolysis. The intermediary effect of procaine hydrochloride is to measure on cellular or subcellular level without compatibility to the activity as a local anaesthetic. With regard to other intermediary effects mentioned in the literature like growth promotion or inhibition of monoamine oxidase activity, it is discussed whether the increase of the hepatic amino acid incorporation rate is corresponding to geriatric experiences made with procaine hydrochloride.

  18. Daily propranolol administration reduces persistent injury-associated anemia after severe trauma and chronic stress.

    PubMed

    Alamo, Ines G; Kannan, Kolenkode B; Bible, Letitia E; Loftus, Tyler J; Ramos, Harry; Efron, Philip A; Mohr, Alicia M

    2017-04-01

    After severe trauma, patients develop a norepinephrine-mediated persistent, injury-associated anemia. This anemia is associated with suppression of bone marrow (BM) erythroid colony growth, along with decreased iron levels, and elevated erythropoietin (EPO) levels, which are insufficient to promote effective erythropoiesis. The impact of norepinephrine on iron regulators, such as ferroportin, transferrin, and transferrin receptor-1 (TFR-1), is unknown. Using a clinically relevant rodent model of lung contusion (LC), hemorrhagic shock (HS), and chronic stress (CS), we hypothesize that daily propranolol (BB), a nonselective β blocker, restores BM function and improves iron homeostasis. Male Sprague-Dawley rats were subjected to LCHS ± BB and LCHS/CS ± BB. BB was achieved with propranolol (10 mg/kg) daily until the day of sacrifice. Hemoglobin, plasma EPO, plasma hepcidin, BM cellularity and BM erythroid colony growth were assessed. RNA was isolated to measure transferrin, TFR-1 and ferroportin expression. Data are presented as mean ± SD; *p < 0.05 versus untreated counterpart by t test. The addition of CS to LCHS leads to persistent anemia on posttrauma day 7, while the addition of BB improved hemoglobin levels (LCHS/CS: 10.6 ± 0.8 vs. LCHS/CS + BB: 13.9 ± 0.4* g/dL). Daily BB use after LCHS/CS improved BM cellularity, colony-forming units granulocyte, erythrocyte, monocyte megakaryocyte, burst-forming unit erythroid and colony-forming unit erythroid cell colony growth. LCHS/CS + BB significantly reduced plasma EPO levels and increased plasma hepcidin levels on day 7. The addition of CS to LCHS resulted in decreased liver ferroportin expression as well as decreased BM transferrin and TFR-1 expression, thus, blocking iron supply to erythroid cells. However, daily BB after LCHS/CS improved expression of all iron regulators. Daily propranolol administration after LCHS/CS restored BM function and improved anemia after severe trauma. In addition, iron regulators are

  19. Daily propranolol administration reduces persistent injury-associated anemia following severe trauma and chronic stress

    PubMed Central

    Alamo, Ines G.; Kannan, Kolenkode B.; Bible, Letitia E.; Loftus, Tyler J.; Ramos, Harry; Efron, Philip A.; Mohr, Alicia M.

    2017-01-01

    Background Following severe trauma, patients develop a norepinephrine-mediated persistent, injury-associated anemia. This anemia is associated with suppression of bone marrow erythroid colony growth, along with decreased iron levels, and elevated erythropoietin (EPO) levels, which are insufficient to promote effective erythropoiesis. The impact of norepinephrine on iron regulators such as ferroportin, transferrin and transferrin receptor-1 (TFR-1) are unknown. Using a clinically relevant rodent model of lung contusion (LC), hemorrhagic shock (HS), and chronic stress (CS), we hypothesize that daily propranolol (BB), a non-selective beta-blocker, restores bone marrow function and improves iron homeostasis. Methods Male Sprague-Dawley rats were subjected to LCHS±BB and LCHS/CS±BB. BB was achieved with propranolol (10mg/kg) daily until the day of sacrifice. Hemoglobin (Hgb), plasma EPO, plasma hepcidin, bone marrow cellularity and bone marrow erythroid colony growth were assessed. RNA was isolated to measure transferrin, TFR-1 and ferroportin expression. Data is presented as mean±SD; *p<0.05 vs. untreated counterpart by t-test. Results The addition of CS to LCHS leads to persistent anemia on post-trauma day 7, while the addition of BB improved Hgb levels (LCHS/CS: 10.6±0.8 vs. LCHS/CS+BB: 13.9±0.4* g/dL). Daily BB use following LCHS/CS improved BM cellularity, CFU-GEMM, BFU-E and CFU-E colony growth. LCHS/CS+BB significantly reduced plasma EPO levels and increased plasma hepcidin levels on day 7. The addition of CS to LCHS resulted in decreased liver ferroportin expression as well as decreased bone marrow transferrin and TFR-1 expression, thus, blocking iron supply to erythroid cells. However, daily BB after LCHS/CS improved expression of all iron regulators. Conclusions Daily propranolol administration following LCHS/CS restored bone marrow function and improved anemia after severe trauma. In addition, iron regulators are significantly reduced following LCHS

  20. Daily oral 25-hydroxycholecalciferol supplementation for vitamin D deficiency in haemodialysis patients: effects on mineral metabolism and bone markers.

    PubMed

    Jean, Guillaume; Terrat, Jean-Claude; Vanel, Thierry; Hurot, Jean-Marc; Lorriaux, Christie; Mayor, Brice; Chazot, Charles

    2008-11-01

    Vitamin D deficiency is frequently observed in end-stage renal disease (ESRD) patients; however, the effects of vitamin D supplementation have rarely been reported. We aimed to assess the effects of daily 25(OH)D(3) supplementation on mineral metabolism, bone markers and Kidney Disease Outcomes Quality Initiative (KDOQI) targets in haemodialysis (HD) patients for a period of 6 months. HD patients were included in this study if their serum 25(OH)D level was <75 mmol/L. Oral 25(OH)D(3) was administered daily at 10-30 microg/day based on the severity of the deficiency. Characteristics of the patients were compared from the baseline to 6 months on the basis of their response to 25(OH)D(3) administration and the patients were divided into three groups. Patients who showed partial response [serum 25(OH)D <75 nmol/L] were placed in group 1, those who showed normal response [serum 25(OH)D ranging from 75 to 150 nmol/L] were placed in group 2 and those who showed excessive response [serum 25(OH)D >150 nmol/L] were placed in group 3. Of the 253 HD patients, 225 (89%) showed vitamin D insufficiency or deficiency, 172 were included in the study and 149 patients completed the study. After 6 months of treatment [mean daily 25(OH)D(3): 16 +/- 5 microg/day], the serum 25(OH)D level increased (30 +/- 19 to 126 +/- 46 nmol/ L, P < 0.001), with 13% of patients in group 1, 57% in group 2 and 30% in group 3. The serum intact parathyroid hormone (iPTH) level decreased (235 +/- 186 to 189 +/- 137 pg/mL, P = 0.05), except in group 1. Bone alkaline phosphatase (BALP) showed a tendency to normalize (23 +/- 16 to 18.3 +/- 11 microg/L, P < 0.05), leading to a decrease in alfacalcidol administration from 66% to 43% (P < 0.05), except in group 1. The KDOQI targets achieved increased significantly for serum calcium (76% to 85%) and phosphate levels (66% to 77%) in all patients. The serum albumin level increased in all groups (34.6 +/- 4 to 36.8 +/- 4 g/L, P < 0.05), without any significant

  1. Effect of daily morphine administration and its discontinuation on delay discounting of food in rhesus monkeys

    PubMed Central

    Maguire, David R; Gerak, Lisa R; France, Charles P

    2015-01-01

    Opioid abusers discount delayed reinforcers more rapidly than non-users; however, it is unclear whether chronic drug administration or its discontinuation impact discounting. This study examined daily morphine administration and its discontinuation on delay discounting of food in rhesus monkeys. Responding on one lever delivered 1 food pellet immediately; responding on another lever delivered 2 food pellets either immediately or after a delay (30–120 sec) that increased within the session. Monkeys (n=3) responded for the large reinforcer when both reinforcers were delivered immediately and more for the smaller, immediately available reinforcer as delay to delivery of the large reinforcer increased. When administered acutely, morphine (0.032–5.6 mg/kg) increased trial omissions and had variable effects on choice, with small doses decreasing and large doses increasing choice of the large delayed reinforcer. Chronic morphine administration (0.1 mg/kg/day to 3.2 mg/kg twice daily) reduced choice of the large delayed reinforcer in two monkeys while increasing choice in a third monkey. Despite the development of tolerance to some effects (i.e., rightward shifts in dose-effect curves for the number of trials omitted) and evidence of mild opioid dependence (e.g., decrease in the number of trials completed as well as body weight), discontinuation of treatment did not appear to systematically impact discounting. Overall, these results suggest that repeated opioid administration causes persistent effects on choice under a delay discounting procedure; however, differences in the direction of effect among individuals suggest factors other than, or in addition to, changes in discounting might play a role. PMID:26397762

  2. Naltrexone Maintenance Decreases Cannabis Self-Administration and Subjective Effects in Daily Cannabis Smokers.

    PubMed

    Haney, Margaret; Ramesh, Divya; Glass, Andrew; Pavlicova, Martina; Bedi, Gillinder; Cooper, Ziva D

    2015-10-01

    Given that cannabis use is increasing in the United States, pharmacological treatment options to treat cannabis use disorder are needed. Opioid antagonists modulate cannabinoid effects and may offer a potential approach to reducing cannabis use. In this double-blind, placebo-controlled human laboratory study, we assessed the effects of naltrexone maintenance on the reinforcing, subjective, psychomotor, and cardiovascular effects of active and inactive cannabis. Nontreatment-seeking, daily cannabis smokers were randomized to receive naltrexone (50 mg: n=18 M and 5 F) or placebo (0 mg; n=26 M and 2 F) capsules for 16 days. Before, during, and after medication maintenance, participants completed 10 laboratory sessions over 4-6 weeks, assessing cannabis' behavioral and cardiovascular effects. Medication compliance was verified by observed capsule administration, plasma naltrexone, and urinary riboflavin. Relative to placebo, maintenance on naltrexone significantly reduced both active cannabis self-administration and its positive subjective effects ('good effect'). Participants in the placebo group had 7.6 times (95% CI: 1.1-51.8) the odds of self-administering active cannabis compared with the naltrexone group. This attenuation of reinforcing and positive subjective effects also influenced cannabis use in the natural ecology. Naltrexone had intrinsic effects: decreasing ratings of friendliness, food intake, and systolic blood pressure, and increasing spontaneous reports of stomach upset and headache, yet dropout rates were comparable between groups. In summary, we show for the first time that maintenance on naltrexone decreased cannabis self-administration and ratings of 'good effect' in nontreatment-seeking daily cannabis smokers. Clinical studies in patients motivated to reduce their cannabis use are warranted to evaluate naltrexone's efficacy as a treatment for cannabis use disorder.

  3. Naltrexone Maintenance Decreases Cannabis Self-Administration and Subjective Effects in Daily Cannabis Smokers

    PubMed Central

    Haney, Margaret; Ramesh, Divya; Glass, Andrew; Pavlicova, Martina; Bedi, Gillinder; Cooper, Ziva D

    2015-01-01

    Given that cannabis use is increasing in the United States, pharmacological treatment options to treat cannabis use disorder are needed. Opioid antagonists modulate cannabinoid effects and may offer a potential approach to reducing cannabis use. In this double-blind, placebo-controlled human laboratory study, we assessed the effects of naltrexone maintenance on the reinforcing, subjective, psychomotor, and cardiovascular effects of active and inactive cannabis. Nontreatment-seeking, daily cannabis smokers were randomized to receive naltrexone (50 mg: n=18 M and 5 F) or placebo (0 mg; n=26 M and 2 F) capsules for 16 days. Before, during, and after medication maintenance, participants completed 10 laboratory sessions over 4–6 weeks, assessing cannabis' behavioral and cardiovascular effects. Medication compliance was verified by observed capsule administration, plasma naltrexone, and urinary riboflavin. Relative to placebo, maintenance on naltrexone significantly reduced both active cannabis self-administration and its positive subjective effects (‘good effect'). Participants in the placebo group had 7.6 times (95% CI: 1.1–51.8) the odds of self-administering active cannabis compared with the naltrexone group. This attenuation of reinforcing and positive subjective effects also influenced cannabis use in the natural ecology. Naltrexone had intrinsic effects: decreasing ratings of friendliness, food intake, and systolic blood pressure, and increasing spontaneous reports of stomach upset and headache, yet dropout rates were comparable between groups. In summary, we show for the first time that maintenance on naltrexone decreased cannabis self-administration and ratings of ‘good effect' in nontreatment-seeking daily cannabis smokers. Clinical studies in patients motivated to reduce their cannabis use are warranted to evaluate naltrexone's efficacy as a treatment for cannabis use disorder. PMID:25881117

  4. Long-term drug administration in the adult zebrafish using oral gavage for cancer preclinical studies

    PubMed Central

    Dang, Michelle; Henderson, Rachel E.; Garraway, Levi A.

    2016-01-01

    ABSTRACT Zebrafish are a major model for chemical genetics, and most studies use embryos when investigating small molecules that cause interesting phenotypes or that can rescue disease models. Limited studies have dosed adults with small molecules by means of water-borne exposure or injection techniques. Challenges in the form of drug delivery-related trauma and anesthesia-related toxicity have excluded the adult zebrafish from long-term drug efficacy studies. Here, we introduce a novel anesthetic combination of MS-222 and isoflurane to an oral gavage technique for a non-toxic, non-invasive and long-term drug administration platform. As a proof of principle, we established drug efficacy of the FDA-approved BRAFV600E inhibitor, Vemurafenib, in adult zebrafish harboring BRAFV600E melanoma tumors. In the model, adult casper zebrafish intraperitoneally transplanted with a zebrafish melanoma cell line (ZMEL1) and exposed to daily sub-lethal dosing at 100 mg/kg of Vemurafenib for 2 weeks via oral gavage resulted in an average 65% decrease in tumor burden and a 15% mortality rate. In contrast, Vemurafenib-resistant ZMEL1 cell lines, generated in culture from low-dose drug exposure for 4 months, did not respond to the oral gavage treatment regimen. Similarly, this drug treatment regimen can be applied for treatment of primary melanoma tumors in the zebrafish. Taken together, we developed an effective long-term drug treatment system that will allow the adult zebrafish to be used to identify more effective anti-melanoma combination therapies and opens up possibilities for treating adult models of other diseases. PMID:27482819

  5. Bioavailability and pharmacokinetics of oral and injectable formulations of methadone after intravenous, oral, and intragastric administration in horses.

    PubMed

    Linardi, Renata L; Stokes, Ashley M; Keowen, Michael L; Barker, Steven A; Hosgood, Giselle L; Short, Charles R

    2012-02-01

    To characterize the bioavailability and pharmacokinetics of oral and injectable formulations of methadone after IV, oral, and intragastric administration in horses. 6 healthy adult horses. Horses received single doses (each 0.15 mg/kg) of an oral formulation of methadone hydrochloride orally or intragastrically or an injectable formulation of the drug orally, intragastrically, or IV (5 experimental treatments/horse; 2-week washout period between each experimental treatment). A blood sample was collected from each horse before and at predetermined time points over a 360-minute period after each administration of the drug to determine serum drug concentration by use of gas chromatography-mass spectrometry analysis and to estimate pharmacokinetic parameters by use of a noncompartmental model. Horses were monitored for adverse effects. In treated horses, serum methadone concentrations were equivalent to or higher than the effective concentration range reported for humans, without induction of adverse effects. Oral pharmacokinetics in horses included a short half-life (approx 1 hour), high total body clearance corrected for bioavailability (5 to 8 mL/min/kg), and small apparent volume of distribution corrected for bioavailability (0.6 to 0.9 L/kg). The bioavailability of methadone administered orally was approximately 3 times that associated with intragastric administration. Absorption of methadone in the small intestine in horses appeared to be limited owing to the low bioavailability after intragastric administration. Better understanding of drug disposition, including absorption, could lead to a more appropriate choice of administration route that would enhance analgesia and minimize adverse effects in horses.

  6. Pharmacokinetics of voriconazole after oral administration of single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis).

    PubMed

    Sanchez-Migallon Guzman, David; Flammer, Keven; Papich, Mark G; Grooters, Amy M; Shaw, Shannon; Applegate, Jeff; Tully, Thomas N

    2010-04-01

    To determine the pharmacokinetics and safety of voriconazole administered orally in single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis). 15 clinically normal adult Hispaniolan Amazon parrots. Single doses of voriconazole (12 or 24 mg/kg) were administered orally to 15 and 12 birds, respectively; plasma voriconazole concentrations were determined at intervals via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) or water was administered orally to 6 and 4 birds, respectively, every 8 hours for 11 days (beginning day 0); trough plasma voriconazole concentrations were evaluated on 3 days. Birds were monitored daily, and clinicopathologic variables were evaluated before and after the trial. Voriconazole elimination half-life was short (0.70 to 1.25 hours). In the single-dose experiments, higher drug doses yielded proportional increases in the maximum plasma voriconazole concentration (C(max)) and area under the curve (AUC). In the multiple-dose trial, C(max), AUC, and plasma concentrations at 2 and 4 hours were decreased on day 10, compared with day 0 values; however, there was relatively little change in terminal half-life. With the exception of 1 voriconazole-treated parrot that developed polyuria, adverse effects were not evident. In Hispaniolan Amazon parrots, oral administration of voriconazole was associated with proportional kinetics following administration of single doses and a decrease in plasma concentration following administration of multiple doses. Oral administration of 18 mg of voriconazole/kg every 8 hours would require adjustment to maintain therapeutic concentrations during long-term treatment. Safety and efficacy of voriconazole treatment in this species require further investigation.

  7. Bioavailability of the Yuzpe and levonorgestrel regimens of emergency contraception: vaginal vs. oral administration.

    PubMed

    Kives, Sari; Hahn, Philip M; White, Emily; Stanczyk, Frank Z; Reid, Robert L

    2005-03-01

    Separate crossover studies compared the bioavailability of oral vs. vaginal routes of administration for the Yuzpe (n=5) and levonorgestrel regimens (n=4) of emergency contraception. Twice the standard dose of the Yuzpe regimen (200 microg of ethinyl estradiol, 1000 microg of levonorgestrel) or the levonorgestrel regimen (1500 microg of levonorgestrel) was self-administered vaginally. One week later, each subject received orally the standard dose of the assigned medication. Serial blood samples were collected over 24 h and assayed for levonorgestrel and ethinyl estradiol (for the Yuzpe regimen only). Paired t tests were used to compare oral vs. vaginal administration for maximum concentration (Cmax), time to maximum concentration (Tmax) and area under the curve over 24 h (AUC0-24). Relative bioavailability (vaginal/oral) was derived from AUC0-24. Vaginal administration of double the standard dose of the Yuzpe regimen resulted in a lower Cmax (vaginal=5.4 vs. oral=14.6 ng/mL, p=.038) and a later Tmax (5.9 vs. 2.0 h, p=.066) for levonorgestrel, compared to oral administration. Corresponding ethinyl estradiol concentrations were higher (786 vs. 391 pg/mL, p=.039) and peaked later (4.0 vs. 1.9 hr, p=.154) with vaginal administration. Relative bioavailabilities for levonorgestrel and ethinyl estradiol were 58% and 175%, respectively. Similarly, vaginal administration of the levonorgestrel regimen resulted in a lower Cmax (vaginal=5.4 vs. oral=15.2 ng/mL, p=.006) and a later Tmax (7.4 vs. 1.3 h, p=.037) for levonorgestel, compared to oral administration. The relative bioavailability was 62%. Our preliminary data suggest that vaginal administration of these emergency contraception regimens appears to require at least three times the standard oral dose to achieve equivalent systemic levonorgestrel concentrations.

  8. Long-Term Oral Administration of Hop Flower Extracts Mitigates Alzheimer Phenotypes in Mice

    PubMed Central

    Sasaoka, Norio; Sakamoto, Megumi; Kanemori, Shoko; Kan, Michiru; Tsukano, Chihiro; Takemoto, Yoshiji; Kakizuka, Akira

    2014-01-01

    Coincident with the expanding population of aged people, the incidence of Alzheimer disease (AD) is rapidly increasing in most advanced countries. At present, no effective prophylactics are available. Among several pathological mechanisms proposed for AD, the “amyloid hypothesis” has been most widely accepted, in which accumulation or deposition of Aβ is considered to be the initial event. Thus, prevention of Aβ production would be an ideal strategy for the treatment or prevention of AD. Aβ is produced via the proteolytic cleavage of its precursor protein, APP (amyloid precursor protein), by two different enzymes, β and γ-secretases. Indeed, inhibitors against either or both enzymes have been developed and tested for clinical efficacy. Based on the “amyloid hypothesis”, we developed a luciferase-based screening method to monitor γ-secretase activity, screened more than 1,600 plant extracts, most of which have long been used in Chinese medicine, and observed that Hop extracts significantly inhibit Aβ production in cultured cells. A major component of the inhibitory activity was purified, and its chemical identity was determined by NMR to be Garcinielliptone HC. In vivo, oral administration of Hop extracts to AD model mice decreased Aβ depositions in the cerebral cortex of the parietal lobe, hippocampus, and artery walls (amyloid angiopathy) in the brains. In a Morris water maze test, AD model mice that had daily consumed Hop extracts in their drinking water showed significant mitigation of memory impairment at ages of 9 and 12 months. Moreover, in the open field test oral administration of Hop extracts also prevented an emotional disturbance that appeared in the AD mice at 18 months. Despite lifelong consumption of Hop extracts, no deleterious side effects were observed at any age. These results support the “amyloid hypothesis”, and indicate that Hop extract is a promising candidate for an effective prophylactic for AD. PMID:24489866

  9. Bioavailability of oxycodone after administration of a new prolonged-release once-daily tablet formulation in healthy subjects, in comparison to an established twice-daily tablet
.

    PubMed

    Scheidel, Bernhard; Maritz, Martina A; Gschwind, Yves J; Steigerwald, Kerstin; Guth, Volker; Kovacs, Peter; Rey, Helene

    2017-11-01

    To evaluate and to compare the bioavailability, the influence of food intake on the bioavailability, and the safety and tolerability of a newly-developed oxycodone once-daily (OOD) prolonged-release tablet with an established oxycodone twice-daily (OTD) prolonged-release tablet after single-dose administration under fasting or fed conditions as well as after multiple-dose administration. Three single-center, open-label, randomized, balanced, two-treatment, two-period, two-sequence crossover studies were conducted. In each study, 36 healthy volunteers were randomized to receive 10 mg oxycodone daily as OOD (oxycodone HCL 10-mg PR tablets XL (Develco Pharma Schweiz AG, Pratteln, Switzerland); administration of 1 tablet in the morning) or as OTD (reference formulation: oxygesic 5-mg tablets (Mundipharma GmbH, Limburg an der Lahn, Germany); administration of 1 tablet in the morning and 1 tablet in the evening). Tablets were administered once daily or twice daily under fasting conditions (study 1) or under fed conditions (study 2) as well as after multiple-dose administration (study 3). A sufficient number of blood samples were taken for describing plasma profiles and for calculation of pharmacokinetic parameters. Plasma concentrations of oxycodone were determined by LC-MS/MS. Safety and tolerability were monitored and assessed in all three studies. Plasma profiles of OOD reveal sustained concentrations of oxycodone over the complete dosing interval of 24 hours. In comparison to the OTD reference formulation, the OOD test formulation showed a slightly slower increase of concentrations within the absorption phase and similar plasma concentrations at the maximum and at the end of the dosing interval (24 hours). Extent of bioavailability (AUC), maximum plasma concentrations (Cmax), and plasma concentrations at the end of the dosing interval (Cτ,ss,24h) of OOD could be classified as comparable to OTD considering 90% confidence intervals (CIs) and

  10. [The impact of oral health on daily performance of municipal waste disposal workers in Porto Alegre, Rio Grande do Sul State, Brazil].

    PubMed

    Gomes, Andréa Silveira; Abegg, Claides

    2007-07-01

    This study aimed to investigate the prevalence of oral health impact on daily performance in Brazilian adults. 276 civil servants 35 to 44 years of age from the Public Works and Waste Disposal Department of Porto Alegre, in southern Brazil, were interviewed and clinically examined. Oral Impacts on Daily Performance (OIDP) was used to evaluate the impact of oral health status on daily performance. 73.6% of all subjects had at least one daily performance affected by an oral impact in the previous six months. The most commonly affected performance was eating (48.6%), while the most common symptoms were discomfort (40.6%) and dissatisfaction with one's appearance (31.5%). Missing teeth (21.7%) and toothache (20.7%) were recognized as the main causes of oral impacts on daily performance. OIDP was useful for measuring (physically, psychologically, and socially) the oral impacts on daily performance.

  11. Tissue, Dosimetry, Metabolism and Excretion of Pentavalent and Trivalent Dimethylated Arsenic in Mice after Oral Administration

    EPA Science Inventory

    Dimethylarsinic acid (DMA(V)) is a rat bladder carcinogen and the major urinary metabolite of administered inorganic arsenic in most mammals. This study examined the disposition of pentavalent and trivalent dimethylated arsenic inmice after acute oral administration. Adult fema...

  12. A case of Diphyllobothrium nihonkaiense infection successfully treated by oral administration of Gastrografin.

    PubMed

    Yoshida, M; Hasegawa, H; Takaoka, H; Miyata, A

    1999-08-01

    A diphyllobothriid cestode infection found in a 54-year-old male residing in Oita, Japan, was successfully treated by oral administration of Gastrografin in combination with a intramuscular injection of Vagostigmin. The strobila expelled was 6.14 m long with a scolex, and morphologically identical with Diphyllobothrium nihonkaiense except unusual ovaries of which posterior horns were confluent in each proglottid. This is the first case of treatment of cestode infection by oral administration of Gastrografin.

  13. The effect of oral protease administration in the rat remnant kidney model.

    PubMed

    Sebeková, K; Dämmrich, J; Krivosíková, Z; Heidland, A

    1999-12-01

    It has been demonstrated that intraperitoneal administration of proteolytic enzymes ameliorates the progression of renal diseases in various animal models. In the present study, we employed the rat remnant kidney model to study the effectiveness of oral administration of proteases. Twenty male Wistar rats underwent sham operation (CTRL), while 25 were subjected to 5/6 nephrectomy (5/6 NX). Rats were randomised into placebo (PL) (2 ml tap water/day by gavage), or Phlogenzym (E; fixed mixture of trypsin 2.42 mg, bromelain 4.54 mg, and rutozid 5.04 mg added as antioxidant, in 2 ml tap water daily by gavage) treated group. Duration of the study was 45 days. Rats were pair-fed. Enzyme treatment exerted salutary effects on various functional and morphological parameters. Proteinuria was higher in both 5/6 NX group rats throughout the study. Administration of proteases ameliorated its rise effectively (data at sacrifice: CTRL-PL 6.27 +/- 1.25, CTRL-E 9.27 +/- 0.99, 5/6 NX-PL 74.04 +/- 21.33, 5/6 NX-E 39.09 +/- 7.93 mg/24 h; P < 0.01). Increased urinary excretion of the fibrogenic cytokine transforming growth factor (TGF-beta 1) was improved, too (CTRL-PL 0.349 +/- 0.051, CTRL-E 0.693 +/- 0.230, 5/6 NX-PL 3.044 +/- 0.540, 5/6 NX-E 1.390 +/- 0.238 ng/mumol creatinine; P < 0.05). At sacrifice, tubulointerstitial fibrosis was less pronounced in E-treated rats. Correspondingly, the volume fraction of tubulointerstitial tissue in the renal cortex was improved in 5/6 NX-E rats (CTRL-PL 9.9 +/- 0.2, CTRL-E 10.0 +/- 0.2, 5/6 NX-PL 17.9 +/- 1.8, 5/6 NX-E 13.8 +/- 0.9%; P < 0.05). The protein/DNA ratio in isolated glomeruli and tubules, as an estimate of glomerular matrix accumulation and hypertrophy of tubules, was enhanced in 5/6 NX groups and a tendency towards lower values was observed after E treatment. Renal function as evaluated by serum creatinine and urea levels was not influenced by the enzyme therapy. No between-group differences in blood pressure were observed. In

  14. The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users.

    PubMed

    Vandrey, Ryan; Stitzer, Maxine L; Mintzer, Miriam Z; Huestis, Marilyn A; Murray, Jeannie A; Lee, Dayong

    2013-02-01

    Prior studies have separately examined the effects of dronabinol (oral THC) on cannabis withdrawal, cognitive performance, and the acute effects of smoked cannabis. A single study examining these clinically relevant domains would benefit the continued evaluation of dronabinol as a potential medication for the treatment of cannabis use disorders. Thirteen daily cannabis smokers completed a within-subject crossover study and received 0, 30, 60 and 120mg dronabinol per day for 5 consecutive days. Vital signs and subjective ratings of cannabis withdrawal, craving and sleep were obtained daily; outcomes under active dose conditions were compared to those obtained under placebo dosing. On the 5th day of medication maintenance, participants completed a comprehensive cognitive performance battery and then smoked five puffs of cannabis for subjective effects evaluation. Each dronabinol maintenance period occurred in a counterbalanced order and was separated by 9 days of ad libitum cannabis use. Dronabinol dose-dependently attenuated cannabis withdrawal and resulted in few adverse side effects or decrements in cognitive performance. Surprisingly, dronabinol did not alter the subjective effects of smoked cannabis, but cannabis-induced increases in heart rate were attenuated by the 60 and 120mg doses. Dronabinol's ability to dose-dependently suppress cannabis withdrawal may be therapeutically beneficial to individuals trying to stop cannabis use. The absence of gross cognitive impairment or side effects in this study supports safety of doses up to 120mg/day. Continued evaluation of dronabinol in targeted clinical studies of cannabis treatment, using an expanded range of doses, is warranted. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. The Dose Effects of Short-Term Dronabinol (Oral THC) Maintenance in Daily Cannabis Users

    PubMed Central

    Vandrey, Ryan; Stitzer, Maxine L.; Mintzer, Miriam Z.; Huestis, Marilyn A.; Murray, Jeannie A.; Lee, Dayong

    2012-01-01

    BACKGROUND Prior studies have separately examined the effects of dronabinol (oral THC) on cannabis withdrawal, cognitive performance, and the acute effects of smoked cannabis. A single study examining these clinically relevant domains would benefit the continued evaluation of dronabinol as a potential medication for the treatment of cannabis use disorders. METHODS Thirteen daily cannabis smokers completed a within-subject crossover study and received 0, 30, 60 and 120 mg dronabinol per day for 5 consecutive days. Vital signs and subjective ratings of cannabis withdrawal, craving and sleep were obtained daily; outcomes under active dose conditions were compared to those obtained under placebo dosing. On the 5th day of medication maintenance, participants completed a comprehensive cognitive performance battery and then smoked 5 puffs of cannabis for subjective effects evaluation. Each dronabinol maintenance period occurred in a counterbalanced order and was separated by 9 days of ad-libitum cannabis use. RESULTS Dronabinol dose-dependently attenuated cannabis withdrawal and resulted in few adverse side effects or decrements in cognitive performance. Surprisingly, dronabinol did not alter the subjective effects of smoked cannabis, but cannabis-induced increases in heart rate were attenuated by the 60 and 120 mg doses. CONCLUSIONS Dronabinol’s ability to dose-dependently suppress cannabis withdrawal may be therapeutically beneficial to individuals trying to stop cannabis use. The absence of gross cognitive impairment or side effects in this study supports safety of doses up to 120mg per day. Continued evaluation of dronabinol in targeted clinical studies of cannabis treatment, using an expanded range of doses, is warranted. PMID:22921474

  16. Urothelial conversion of 5-aminolevulinic acid to protoporphyrin IX following oral or intravesical administration

    NASA Astrophysics Data System (ADS)

    Moore, Ronald B.; Miller, Gerald G.; Brown, Kevin; Bhatnagar, Rakesh; Tulip, John; McPhee, Malcolm S.

    1995-03-01

    Preferential conversion of 5-aminolevulinic acid (5-ALA) to protoporphyrin-IX (Pp-IX) occurs in malignant tissue, with accumulation to diagnostic and therapeutic levels. Recent studies have suggested selective conversion in epithelial tissue following oral or intravenous administration. Topical application avoids systemic photosensitization. However, the glycosaminoglycan (GAG) layer lining the urinary bladder is believed to be a protective barrier generally limiting mucosal absorption. Our objective was to evaluate uptake and conversion of 5-ALA following intravesical or oral administration. Using a rat model, Pp-IX content within epithelial and muscularis layers was quantitated by fluorescence confocal microscopy. Following intravesical administration, Pp-IX accumulated predominantly in the urothelium; whereas following oral administration, Pp-IX accumulated in both the urothelium and muscularis. Intravesical 5-ALA administration is feasible and may afford selective photosensitization of the urothelium for treatment of carcinoma in situ.

  17. Factors influencing the impact of oral health on the daily activities of adolescents, adults and older adults

    PubMed Central

    Bulgareli, Jaqueline Vilela; de Faria, Eduardo Tanajura; Cortellazzi, Karine Laura; Guerra, Luciane Miranda; Meneghim, Marcelo de Castro; Ambrosano, Glaucia Maria Bovi; Frias, Antonio Carlos; Pereira, Antonio Carlos

    2018-01-01

    ABSTRACT OBJECTIVE: Analyze if clinical, sociodemographic and access to dental services variables influence the impact of oral health on the daily activities of adolescents, adults and older adults. METHODS: A cross-sectional study with secondary data from the State Oral Health Survey (SB São Paulo 2015) conducted in 163 cities of São Paulo. A total of 17,560 individuals from three age groups: 15–19-year-old (n = 5,558), 35–44-year-old (n = 6,051), and older people of 65 years or more (n = 5,951) participated in the survey. The selection was made by probabilistic sample by conglomerates in two stages. The endpoint variable was the impact of oral health on daily activities, evaluated by the Oral Impacts on Daily Performances questionnaire, containing questions about eating, talking, oral hygiene, relaxation, sports practice, smile, study or work, social contact, and sleep. Oral Impacts on Daily Performances was dichotomized with and without impact. The independent variables were sociodemographic, clinical and access variables, divided into three blocks. A hierarchical multiple logistic regression analysis was performed considering the complex sampling plan of clusters. Each observation received a specific weight, depending on the location that resulted in weighted frequencies and adjusted for the design effect. RESULTS: The presence of oral health impact was observed in 27.9% of the individuals. In block 1, female gender and black/brown ethnic group had a greater chance of impact of oral health on quality of life, as well as the adults and the older adults in relation to adolescents. In block 2, family income up to R$1,500 was associated with the presence of impact. In block 3, individuals who reported toothache, used the public service and sought dental treatment had a greater chance of impact. CONCLUSIONS: Sociodemographic, clinical and access to health services variables influence the impact of oral health on the daily activities of adolescents, adults and

  18. Sublingual and oral morphine administration. Review and new findings.

    PubMed

    Robison, J M; Wilkie, D J; Campbell, B

    1995-12-01

    Clinical reports rave about the efficacy of sublingual morphine, but most research data suggest that sublingual morphine lacks the necessary physical characteristics to be absorbed through sublingual tissues. This article clarifies these assertions by reviewing the clinical literature that supports sublingual administration, the theories relevant to sublingual morphine administration, and the pharmacokinetic research that supports or negates the benefit of this route. Recommendations for clinical nursing practice are provided to guide decision-making in care of patients with cancer pain.

  19. Estimation of the total daily oral intake of NDMA attributable to drinking water.

    PubMed

    Fristachi, Anthony; Rice, Glenn

    2007-09-01

    Disinfection with chlorine and chloramine leads to the formation of many disinfection by-products including N-Nitrosodimethylamine (NDMA). Because NDMA is a probable human carcinogen, public health officials are concerned with its occurrence in drinking water. The goal of this study was to estimate NDMA concentrations from exogenous (i.e., drinking water and food) and endogenous (i.e., formed in the human body) sources, calculate average daily doses for ingestion route exposures and estimate the proportional oral intake (POI) of NDMA attributable to the consumption of drinking water relative to other ingestion sources of NDMA. The POI is predicted to be 0.02% relative to exogenous and endogenous NDMA sources combined. When only exogenous sources are considered, the POI was predicted to be 2.7%. The exclusion of endogenously formed NDMA causes the POI to increase dramatically, reflecting its importance as a potentially major source of exposure and uncertainty in the model. Although concentrations of NDMA in foods are small and human exposure to NDMA from foods is quite low, the contribution from food is predicted to be high relative to that of drinking water. The mean concentration of NDMA in drinking water would need to increase from 2.1 x 10(-3) microg/L to 0.10 microg/L, a 47-fold increase, for the POI to reach 1%, relative to all sources of NDMA considered in our model, suggesting that drinking water consumption is most likely a minor source of NDMA exposure.

  20. Comparison of prospective daily diaries and retrospective recall to measure oral contraceptive adherence.

    PubMed

    Huber, Larissa R Brunner; Broel, Elizabeth C; Mitchelides, Ashley N; Dmochowski, Jacek; Dulin, Michael; Scholes, Delia

    2013-10-01

    The purpose of this study was to determine if retrospective recall of oral contraceptive (OC) adherence provides data that are similar to data collected via daily diaries over the same time period. Factors associated with inconsistent agreement between prospective and retrospective measurements of adherence also were explored. A total of 185 women participated in a longitudinal, prospective cohort of OC users, and 113 of these women provided complete information on OC adherence during follow-ups. Concordance beyond chance was assessed using weighted kappa statistics, and logistic regression was used to identify factors associated with inconsistent reporting of adherence. There was substantial agreement between prospective and retrospective adherence information (weighted kappa=0.64; 95% CI: 0.52-0.77). Participants with a high school education or less and those who had problems with feeling sad while using OCs had increased odds of inconsistent reporting of adherence (OR=4.38, 95% CI: 1.41-13.61 and OR=3.52, 95% CI: 1.25-9.94, respectively). While prospective data collection via diaries may improve accuracy, the added expense and burden on study participants may not be necessary. However, the use of retrospective recall may not be appropriate for all study populations. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Weight change with oral contraceptive use and during the menstrual cycle. Results of daily measurements.

    PubMed

    Rosenberg, M

    1998-12-01

    Although weight gain is among the most common complaints of women using oral contraceptives (OC) and a frequent reason for discontinuation, studies demonstrate little basis for this perception. We explored this issue by analyzing the daily weights of 128 women during four cycles of triphasic OC use. The mean weight at the end of the fourth cycle of use was the same as baseline weight (average weight change, 0.0 pounds). The largest proportion of women, 52%, remained within 2 pounds (0.9 kg) of their starting weight, and 72% of women had either no weight change or a loss. Over each menstrual cycle, regular but minor weight shifts were observed, with the mean weight rising by one-half pound (0.2 kg) during the first weeks of each cycle and falling by the same amount during the last few days. These results emphasize the lack of association of OC use with weight gain but OC may be blamed at least in part, based on cyclic fluctuations. Counseling should emphasize weight gain as a misperception and stress the fact that a highly effective and safe form of contraception should not be ruled out or discontinued because of concern about weight.

  2. Intra-oral administration of rebamipide liquid prevents tongue injuries induced by X-ray irradiation in rats.

    PubMed

    Nakashima, Takako; Uematsu, Naoya; Sakurai, Kazushi

    2017-07-01

    Oral mucositis is a common and serious side effect in patients who undergo cytotoxic cancer therapies. The purpose of this study was to investigate the preventive effects of rebamipide on radiation-induced glossitis model in rats. Glossitis was induced by a single dose of 15 Gy of X-rays to the snouts of rats (day 0). A novel form of rebamipide liquid comprising its submicronized crystals was administered intra-orally. The preventive effect of rebamipide on tongue injuries was macroscopically evaluated on day 7 following irradiation. The pretreatment period, dosing frequency, and dose dependency of rebamipide were examined. Two percent rebamipide liquid, administered six times a day for 14 days from day -7 to day 6, significantly decreased the ulcer-like area. However, no significant effect was observed when rebamipide was given either from day -4 or from day -1. Four or six times daily, 2% rebamipide liquid significantly inhibited the ulcer-like injury area ratio, but not when given twice daily. Rebamipide liquid, 1, 2, and 4% six times daily significantly reduced the area ratios of total injury and ulcer-like injury in a dose-dependent manner. Gene expression and protein levels of proinflammatory cytokines and chemokines were dramatically elevated in the irradiated tongues of control rats on day 7 without rebamipide liquid treatment. They were dose-dependently and significantly suppressed in rebamipide-treated groups. Intra-oral administration of rebamipide liquid prevented oral mucositis dose-dependently accompanied by the suppression of inflammatory expression in the radiation-induced rats' glossitis model.

  3. Cost effectiveness of once-daily oral chelation therapy with deferasirox versus infusional deferoxamine in transfusion-dependent thalassaemia patients: US healthcare system perspective.

    PubMed

    Delea, Thomas E; Sofrygin, Oleg; Thomas, Simu K; Baladi, Jean-Francois; Phatak, Pradyumna D; Coates, Thomas D

    2007-01-01

    Deferasirox is a recently approved once-daily oral iron chelator that has been shown to reduce liver iron concentrations and serum ferritin levels to a similar extent as infusional deferoxamine. To determine the cost effectiveness of deferasirox versus deferoxamine in patients with beta-thalassaemia major from a US healthcare system perspective. A Markov model was used to estimate the total additional lifetime costs and QALYs gained with deferasirox versus deferoxamine in patients with beta-thalassaemia major and chronic iron overload from blood transfusions. Patients were assumed to be 3 years of age at initiation of chelation therapy and to receive prescribed dosages of deferasirox and deferoxamine that have been shown to be similarly effective in such patients. Compliance with chelation therapy and probabilities of iron overload-related cardiac disease and death by degree of compliance were estimated using data from published studies. Costs ($US, year 2006 values) of deferoxamine administration and iron overload-related cardiac disease were based on analyses of health insurance claims of transfusion-dependent thalassaemia patients. Utilities were based on a study of patient preferences for oral versus infusional chelation therapy, as well as published literature. Probabilistic and deterministic sensitivity analyses were employed to examine the robustness of the results to key assumptions. Deferasirox resulted in a gain of 4.5 QALYs per patient at an additional expected lifetime cost of $US126,018 per patient; the cost per QALY gained was $US28,255. The cost effectiveness of deferasirox versus deferoxamine was sensitive to the estimated costs of deferoxamine administration and the quality-of-life benefit associated with oral versus infusional therapy. Cost effectiveness was also relatively sensitive to the equivalent daily dose of deferasirox, and the unit costs of deferasirox and deferoxamine, and was more favourable in younger patients. Results of this analysis

  4. Pharmacokinetics of fluralaner in dogs following a single oral or intravenous administration.

    PubMed

    Kilp, Susanne; Ramirez, Diana; Allan, Mark J; Roepke, Rainer K A; Nuernberger, Martin C

    2014-03-07

    Fluralaner is a novel systemic insecticide and acaricide. The purpose of these studies was to investigate the pharmacokinetic properties of fluralaner in Beagle dogs following single oral or intravenous (i.v.) administration. Following the oral administration of 12.5, 25 or 50 mg fluralaner/kg body weight (BW), formulated as chewable tablets or i.v. administration of 12.5 mg fluralaner/kg BW, formulated as i.v. solution to 24 Beagles, plasma samples were collected until 112 days after treatment. Plasma concentrations of fluralaner were measured using HPLC-MS/MS. Pharmacokinetic parameters were calculated by non-compartmental methods. After oral administration, maximum plasma concentrations (C(max)) were reached within 1 day on average. Fluralaner was quantifiable in plasma for up to 112 days after single oral and i.v. treatment. The apparent half-life of fluralaner was 12-15 days and the mean residence time was 15-20 days. The apparent volume of distribution of fluralaner was 3.1 L/kg, and clearance was 0.14 L/kg/day. Fluralaner is readily absorbed after single-dose oral administration, and has a long elimination half-life, long mean residence time, relatively high apparent volume of distribution, and low clearance. These pharmacokinetic characteristics help to explain the prolonged activity of fluralaner against fleas and ticks on dogs after a single oral dose.

  5. Disintegration of chemotherapy tablets for oral administration in patients with swallowing difficulties.

    PubMed

    Siden, Rivka; Wolf, Matthew

    2013-06-01

    The administration of oral chemotherapeutic drugs can be problematic in patients with swallowing difficulties. Inability to swallow solid dosage forms can compromise compliance and may lead to poor clinical outcome. The current technique of tablet crushing to aid in administration is considered an unsafe practice. By developing a technique to disintegrate tablets in an oral syringe, the risk associated with tablet crushing can be avoided. The purpose of this study was to determine the feasibility of using disintegration in an oral syringe for the administration of oral chemotherapeutic tablets. Eight commonly used oral chemotherapeutic drugs were tested. Tablets were placed in an oral syringe and allowed to disintegrate in tap water. Various volumes and temperatures were tested to identify which combination allows for complete disintegration of the tablet in the shortest amount of time. The oral syringe disintegration method was considered feasible if disintegration occurred in ≤15 min and in ≤20 mL of water and the dispersion passed through an oral syringe tip. The following tablets were shown to disintegrate within 15 min and in <20 mL of water: busulfan, cyclophosphamide 50 mg, dasatinib, imatinib, methotrexate, and thioguanine. For these drugs, drug-specific information pamphlets can be prepared for patient or caregiver use. Mercaptopurine, cyclophosphamide 25 mg, and mitotane tablets did not pass the disintegration test. Disintegrating oral chemotherapeutic tablets in a syringe provides a closed system to administer hazardous drugs and allows for the safe administration of oral chemotherapeutic drugs in a tablet form to patients with swallowing difficulties.

  6. 77 FR 41415 - Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-13

    ... INFORMATION CONTACT: Astrid Lopez-Goldberg, Center for Drug Evaluation and Research, Food and Drug... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0563] Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration and...

  7. [Mucopenetrating nanoparticles: vehicles for the oral administration of paclitaxel].

    PubMed

    Zabaleta, V; Calleja, P; Espuelas, S; Corrales, L; Pío, R; Agüeros, M; Irache, J M

    2013-03-01

    Paclitaxel is an anticancer drug used as solution for perfusion for the treatment of certain types of cancers. In the last years, a number of strategies have been proposed for the development of an oral formulation of this drug. However, this task is quite complicated due to the poor aqueous solubility of paclitaxel as well as the fact that this compound is substrate of the intestinal P-glycoprotein and the cytochrome P450 enzymatic complex. In this work, we have developed pegylated nanoparticles with mucopenetrating properties in order to conduct paclitaxel onto the surface of the enterocyte. These nanoparticles displayed a size of about 180 nm and a drug loading close to 15% by weight. The pharmacokinetic study in mice has shown that these nanoparticles were capable to offer therapeutic plasma levels of paclitaxel up to 72 hours. In addition, the oral relative bioavailability of paclitaxel when loaded in nanoparticles pegylated with poly(ethylene glycol) 2000 (PEG) was found to be 85%. In a subcutaneous model of tumour in mice, these pegylated nanoparticles administered orally every 3 days have demonstrated a similar efficacy than Taxol® administered intravenously every day during 9 days. All of these results suggested that these pegylated nanoparticles were capable to cross the mucus layer of the gut and, then, reach the surface of the enterocytes. The PEG molecules would facilitate the adhesion of nanoparticles to this epithelial surface, minimise the pre-systemic metabolism of paclitaxel and, thus, promote its absorption. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  8. Metabolomic Analyses of Blood Plasma after Oral Administration of D-Glucosamine Hydrochloride to Dogs

    PubMed Central

    Osaki, Tomohiro; Azuma, Kazuo; Kurozumi, Seiji; Takamori, Yoshimori; Tsuka, Takeshi; Imagawa, Tomohiro; Okamoto, Yoshiharu; Minami, Saburo

    2012-01-01

    D-Glucosamine hydrochloride (GlcN∙HCl) is an endogenous amino monosaccharide synthesized from glucose that is useful in the treatment of joint diseases in both humans and animals. The aim of this study was to examine amino acid metabolism in dogs after oral administration of GlcN∙HCl. Accelerated fumarate respiration and elevated plasma levels of lactic acid and alanine were observed after administration. These results suggest that oral administration of GlcN∙HCl induces anaerobic respiration and starvation in cells, and we hypothesize that these conditions promote cartilage regeneration. Further studies are required to evaluate the expression of transforming growth factor-beta (TGF-β). PMID:23015778

  9. Oral transmucosal administration of dexmedetomidine for sedation in 4 dogs

    PubMed Central

    Cohen, Anne E.; Bennett, Sara L.

    2015-01-01

    Injectable dexmedetomidine (DM) is widely used for sedation, restraint, anxiolysis, and analgesia in veterinary medicine. Oral transmucosal dexmedetomidine (OTM DM) has been evaluated in horses, cats, and humans, but not in dogs. In this case series, OTM DM (mean dose of 32.6 μg/kg body weight) was given in the buccal pouch to 4 aggressive dogs in a hospital setting. Two of the dogs were subsequently euthanized, and in the other 2, sedation was reversed with atipamezole. Satisfactory sedation was achieved in all cases. PMID:26538668

  10. Oral transmucosal administration of dexmedetomidine for sedation in 4 dogs.

    PubMed

    Cohen, Anne E; Bennett, Sara L

    2015-11-01

    Injectable dexmedetomidine (DM) is widely used for sedation, restraint, anxiolysis, and analgesia in veterinary medicine. Oral transmucosal dexmedetomidine (OTM DM) has been evaluated in horses, cats, and humans, but not in dogs. In this case series, OTM DM (mean dose of 32.6 μg/kg body weight) was given in the buccal pouch to 4 aggressive dogs in a hospital setting. Two of the dogs were subsequently euthanized, and in the other 2, sedation was reversed with atipamezole. Satisfactory sedation was achieved in all cases.

  11. Oral chronic ethanol administration to rodents by agar gel diet.

    PubMed

    Bykov, I; Palmén, M; Piirainen, L; Lindros, K O

    2004-01-01

    Chronic ethanol administration to rodents requires specially designed equipment and is labor intensive. Here we report a new procedure. A commercial liquid diet preparation was made into a gel by addition of 0.5% agar. The gel, containing 5.3% ethanol, was offered in Falcon tubes equipped with a feeding opening. The gel consumption by C57/Bl mice resulted in high blood ethanol levels (average 43 mM). After 6 weeks, marked liver steatosis and significantly increased serum alanine aminotransferase levels had developed. Administration of ethanol in a nutritionally adequate gel provides a simple method for studies on chronic ethanol effects in rodents.

  12. Oral or vaginal misoprostol administration for induction of labor: a randomized, double-blind trial.

    PubMed

    Adair, C D; Weeks, J W; Barrilleaux, S; Edwards, M; Burlison, K; Lewis, D F

    1998-11-01

    To compare the efficacy and vaginal birth intervals after intravaginal or oral misoprostol for labor induction. One hundred seventy-eight women were randomized to one of two double-blind groups: 1) oral misoprostol 200 microg and one-half tablet placebo intravaginal or 2) oral placebo tablet and one-half tablet of a 100-microg misoprostol intravaginal (dose 50 microg). Doses were repeated every 6 hours until labor was established (maximum of three doses). Ninety-three subjects were assigned to oral misoprostol and 85 to intravaginal administration. Oral administration was accompanied by significantly shorter intervals to the onset of uterine contractility (133+/-78 minutes versus 168+/-93, P < .01) but a higher incidence of abnormal uterine contractile activity (tachysystole 38.7% versus 20.0%, P < .01; hyperstimulation syndrome 44.1% versus 21.2%, P < .01). No adverse maternal or neonatal outcomes were noted, nor were there differences in cesarean delivery rates or total lengths of labor. Oral administration of 200 microg misoprostol has similar efficacy to intravaginal administration of 50 microg but is associated with more frequent abnormal uterine contractility.

  13. Effects of oral administration of titanium dioxide fine-sized particles on plasma glucose in mice.

    PubMed

    Gu, Ning; Hu, Hailong; Guo, Qian; Jin, Sanli; Wang, Changlin; Oh, Yuri; Feng, Yujie; Wu, Qiong

    2015-12-01

    Titanium dioxide (TiO2) is an authorized additive used as a food colorant, is composed of nano-sized particles (NP) and fine-sized particles (FP). Previous study reported that oral administration of TiO2 NPs triggers an increase in plasma glucose of mice. However, no previous studies have focused on toxic effects of TiO2 FPs on plasma glucose homeostasis following oral administration. In the current study, mice were orally administered TiO2 FPs greater than 100 nm in size (64 mg/kg body weight per day), and effects on plasma glucose levels examined. Our results showed that titanium levels was not changed in mouse blood, livers and pancreases after mice were orally administered TiO2 FPs. Biochemical analyzes showed that plasma glucose and ROS levels were not affected by TiO2 FPs. Histopathological results showed that TiO2 FPs did not induce pathology changes in organs, especially plasma glucose homeostasis regulation organs, such as pancreas and liver. Western blotting showed that oral administration of TiO2 FPs did not induce insulin resistance (IR) in mouse liver. These results showed that, TiO2 FPs cannot be absorbed via oral administration and affect plasma glucose levels in mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Bioequivalence study between two formulations of ciclosporin A (Cyclavance® oral solution and Atopica® soft capsules) following a single oral administration to dogs.

    PubMed

    Navarro, C; Séguy, L; Vila, M; Birckel, P

    2016-03-12

    Ciclosporin is a selective immunomodulator used for the treatment of atopic dermatitis in dogs. A new 100 mg/ml oral solution formulation (Cyclavance®, Virbac) was developed as a pharmaceutical equivalent to the marketed capsule formulations (Atopica®, Novartis Animal Health) containing 25, 50 mg, or 100 mg of ciclosporin A. The aim of this study was to assess and compare the pharmacokinetic profiles and bioequivalence of the two formulations following a single oral administration to dogs. This randomised, two-period, two-sequence, crossover bioequivalence study was conducted in 40 healthy dogs under fasting conditions. Each dog received either one 50 mg capsule of Atopica® or 0.5 ml of Cyclavance®. After dosing, blood samples were collected during a 48-h time period at 0, 0.5, 1, 2, 4, 6, 12, 24, 36 and 48 h. Blood ciclosporin A concentrations were measured by using an HPLC-MS/MS method. Cmax, Tmax, t1/2, AUC0-t, AUC0-∞ and Kel were determined for the two ciclosporin formulations. Bioequivalence was to be concluded if the 90% confidence intervals were within the range of 80% to 125% for Cmax and AUC0-t. Dogs were monitored once daily throughout the study period for adverse effects. The 90% confidence intervals for Cyclavance®/Atopica® mean ratios of the log-transformed pharmacokinetic variables Cmax and AUC0-t were within the conventional bioequivalence range of 80% to 125% (Point estimate: 101.2% and 101.4% respectively). Except for salivation reported after administration of both products, or vomiting and diarrhoea reported after Atopica® administration, both formulations were well tolerated in the 40 healthy dogs over the 48-h study period. The two ciclosporin oral formulations demonstrated similar pharmacokinetic profiles and were found to be bioequivalent, and therefore, interchangeable.

  15. BEHAVIORAL AND NEUROCHEMICAL OUTCOMES OF REPEATED ORAL ADMINISTRATION OF CHLORPYRIFOS IN POSTNATAL/JUVENILE RATS.

    EPA Science Inventory

    Concern has been raised regarding potential adverse effects on the nervous system following childhood exposure to chlorpyrifos (O,O-diethyl-O-3,5,6-trichloro-2-pyridyl-phosphorothioate). This study examined the outcomes of daily oral dosing with chlorpyrifos, from early postnata...

  16. Preparation and evaluation of gelling granules to improve oral administration.

    PubMed

    Ito, Ikumi; Ito, Akihiko; Unezaki, Sakae

    2015-06-01

    We investigated the preparation of oral granules that are solid when stored and that will swell and gel via water absorption, to address problems experienced by patients when taking medication. Important physical properties of gelling granules include elasticity that is normally smooth, quick water absorption and swelling properties that allow easy swallowing. We selected gelatin (GEL), succinylated gelatin (SUC-GEL) and ι-carrageenan (CAR) as matrix polymers that can undergo gelation at room temperature or at cold temperatures. Saccharide and polyethylene glycol (PEG) were added to prepare the experimental granules. The best matrix gelling granule was SUC-GEL. When xylitol (XYL), sorbitol (SOR) and maltitol (MAL) were added, elasticity was improved, and PEG improved the granule's water absorption behavior, which is an important element involved in gelation. The best granules were prepared by selecting SUC-GEL as the matrix and adding a small amount of PEG and XYL in amounts equal to that of SUC-GEL.

  17. Comparative pharmacokinetics of chlorogenic acid after oral administration in rats

    PubMed Central

    Qi, Wei; Zhao, Ting; Yang, Wen-Wen; Wang, Guang-Hou; Yu, Hua; Zhao, Hai-Xiao; Yang, Chen; Sun, Li-Xin

    2011-01-01

    The present study was aimed at the comparison of the pharmacokinetics of pure chlorogenic acid and extract of Solanum lyratum Thunb. The animals were allocated to two groups, and were administered chlorogenic acid or extract of S. lyratum Thunb. at a dose of 50.0 mg/kg orally. Blood samples were collected up to 8 h post-dosing. Plasma chlorogenic acid analyses were performed using an HPLC method with UV detector. The pharmacokinetic parameters were evaluated using non-compartmental assessment. Significant differences existed in the two groups for AUC0−t, AUC0−∞ and CLz/F. The reliable HPLC method was successfully applied to the determination of chlorogenic acid in rat plasma at dosage of 50.0 mg/kg. PMID:29403709

  18. Clonic Seizures in GAERS Rats after Oral Administration of Enrofloxacin

    PubMed Central

    Bauquier, Sebastien H; Jiang, Jonathan L; Lai, Alan; Cook, Mark J

    2016-01-01

    The aim of this study was to evaluate the effect of oral enrofloxacin on the epileptic status of Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Five adult female GAERS rats, with implanted extradural electrodes for EEG monitoring, were declared free of clonic seizures after an 8-wk observation period. Enrofloxacin was then added to their drinking water (42.5 mg in 750 mL), and rats were observed for another 3 days. The number of spike-and-wave discharges and mean duration of a single discharge did not differ before and after treatment, but 2 of the 5 rats developed clonic seizures after treatment. Enrofloxacin should be used with caution in GAERS rats because it might induce clonic seizures. PMID:27298247

  19. Doxycycline depletion and residues in eggs after oral administration to laying hens.

    PubMed

    Gajda, Anna; Posyniak, Andrzej

    2015-01-01

    The depletion of doxycycline (DC) residues in eggs was determined after oral drug administration by drinking water to laying hens. The antibiotic was supplied to birds for 5 consecutive days and the eggs were collected during medication and 18 days after withdrawal. DC residues were determined by LC-MS/MS. DC was isolated from eggs with a solution of 0.02 M of oxalic acid (pH 4), 0.1 M Na2EDTA and acetonitrile. The limit of detection (LOD) and limit of quantification (LOQ) of the method were 2 and 5 µg kg(-1), respectively. Analyses were performed on whole egg, egg white and yolk separately. DC was detectable 24 h after the beginning of administration. The concentration of antibiotic increased daily, resulting in the highest DC concentration in whole eggs at the first day of the withdrawal period. Thirteen days after withdrawal, the content of DC in whole eggs was below the LOQ of the method. However, some differences were found in the depletion curve of DC between egg white and yolk. Residues of DC in egg white were much higher during treatment and 1 day after withdrawal, but later the concentration in egg white decreased fairly rapidly and a higher DC content in egg yolk was observed. The depletion period was shorter for egg white than for yolk, and DC was detected in the egg white until 12 days after withdrawal and 2 days more in egg yolk than in white. DC reached a peak faster in egg white, but the residues were detectable for longer period in the yolk.

  20. Effects of oral megestrol acetate administration on the hypothalamic-pituitary-adrenal axis of male bottlenose dolphins (Tursiops truncatus).

    PubMed

    Houser, Dorian S; Champagne, Cory D; Jensen, Eric D; Smith, Cynthia R; Cotte, Lara S; Meegan, Jenny M; Booth, Rebecca K; Wasser, Samuel K

    2017-07-15

    OBJECTIVE To evaluate the impact of oral megestrol acetate (MA) administration on adrenal function in male bottlenose dolphins (Tursiops truncatus). DESIGN Serial cross-sectional study. ANIMALS 8 adult male dolphins, all of which were receiving MA at various daily doses (range, 0 to 60 mg, PO) for the control of reproductive behavior. PROCEDURES Blood samples were collected every 2 weeks for 1 year from dolphins trained to voluntarily provide them. Cortisol, ACTH, and other hormone concentrations were measured in serum or plasma via radioimmunoassay or ELISA. Fecal samples, also provided by dolphins voluntarily, were assayed for glucocorticoid metabolite concentrations. Effects of daily MA dose on hormone concentrations were evaluated. RESULTS Daily MA doses as low as 10 mg strongly suppressed cortisol secretion in nearly all dolphins, and except for a single measurement, no dolphin had measurable serum concentrations at doses ≥ 20 mg. Variations in serum cortisol concentration were unrelated to season but were directly related to ACTH concentrations, suggesting primary effects upstream of the adrenal gland. Cessation of MA administration resulted in almost immediate restoration of measurable serum cortisol concentrations, although concentrations continued to rise in a few dolphins over the following weeks to months. CONCLUSIONS AND CLINICAL RELEVANCE Caution should be exercised when administering MA to control reproductive behavior in male dolphins. Because the hypothalamic-pituitary-adrenal axis appeared to be sensitive to even small doses of MA in dolphins, duration of treatment may be the most critical consideration.

  1. A Malay version of the Child Oral Impacts on Daily Performances (Child-OIDP) index: assessing validity and reliability.

    PubMed

    Yusof, Zamros Y M; Jaafar, Nasruddin

    2012-06-08

    The study aimed to develop and test a Malay version of the Child-OIDP index, evaluate its psychometric properties and report on the prevalence of oral impacts on eight daily performances in a sample of 11-12 year old Malaysian schoolchildren. The Child-OIDP index was translated from English into Malay. The Malay version was tested for reliability and validity on a non-random sample of 132, 11-12 year old schoolchildren from two urban schools in Kuala Lumpur. Psychometric analysis of the Malay Child-OIDP involved face, content, criterion and construct validity tests as well as internal and test-retest reliability. Non-parametric statistical methods were used to assess relationships between Child-OIDP scores and other subjective outcome measures. The standardised Cronbach's alpha was 0.80 and the weighted Kappa was 0.84 (intraclass correlation = 0.79). The index showed significant associations with different subjective measures viz. perceived satisfaction with mouth, perceived needs for dental treatment, perceived oral health status and toothache experience in the previous 3 months (p < 0.05). Two-thirds (66.7%) of the sample had oral impacts affecting one or more performances in the past 3 months. The three most frequently affected performances were cleaning teeth (36.4%), eating foods (34.8%) and maintaining emotional stability (26.5%). In terms of severity of impact, the ability to relax was most severely affected by their oral conditions, followed by ability to socialise and doing schoolwork. Almost three-quarters (74.2%) of schoolchildren with oral impacts had up to three performances affected by their oral conditions. This study indicated that the Malay Child-OIDP index is a valid and reliable instrument to measure the oral impacts of daily performances in 11-12 year old urban schoolchildren in Malaysia.

  2. Pharmacokinetics of terbinafine after oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

    PubMed

    Evans, Erika E; Emery, Lee C; Cox, Sherry K; Souza, Marcy J

    2013-06-01

    To determine pharmacokinetics after oral administration of a single dose of terbinafine hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 6 healthy adult Hispaniolan Amazon parrots. A single dose of terbinafine hydrochloride (60 mg/kg) was administered orally to each bird, which was followed immediately by administration of a commercially available gavage feeding formula. Blood samples were collected at the time of drug administration (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Plasma concentrations of terbinafine were determined via high-performance liquid chromatography. Data from 1 bird were discarded because of a possible error in the dose of drug administered. After oral administration of terbinafine, the maximum concentration for the remaining 5 fed birds ranged from 109 to 671 ng/mL, half-life ranged from 6 to 13.5 hours, and time to the maximum concentration ranged from 2 to 8 hours. No adverse effects were observed. Analysis of the results indicated that oral administration of terbinafine at a dose of 60 mg/kg to Amazon parrots did not result in adverse effects and may be potentially of use in the treatment of aspergillosis. Additional studies are needed to determine treatment efficacy and safety.

  3. Intraluminal Administration of Poly I:C Causes an Enteropathy That Is Exacerbated by Administration of Oral Dietary Antigen

    PubMed Central

    Araya, Romina E.; Jury, Jennifer; Bondar, Constanza

    2014-01-01

    Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics virally-induced activation of TLR3 signalling causing acute small intestine damage, but whether and how mucosal administration of poly I:C causes enteropathy is less clear. Our aim was to investigate the inflammatory pathways elicited after intraluminal administration of poly I:C and determine acute and delayed consequences of this locally induced immune activation. Intraluminal poly I:C induced rapid mucosal immune activation in C57BL/6 mice involving IFNβ and the CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile. Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin-sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration of gliadin. Our results indicate that small intestine pathology can be induced in mice by intraluminal administration of poly I:C and that this is exacerbated by subsequent oral delivery of a relevant dietary antigen. PMID:24915573

  4. Intraluminal administration of poly I:C causes an enteropathy that is exacerbated by administration of oral dietary antigen.

    PubMed

    Araya, Romina E; Jury, Jennifer; Bondar, Constanza; Verdu, Elena F; Chirdo, Fernando G

    2014-01-01

    Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics virally-induced activation of TLR3 signalling causing acute small intestine damage, but whether and how mucosal administration of poly I:C causes enteropathy is less clear. Our aim was to investigate the inflammatory pathways elicited after intraluminal administration of poly I:C and determine acute and delayed consequences of this locally induced immune activation. Intraluminal poly I:C induced rapid mucosal immune activation in C57BL/6 mice involving IFNβ and the CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile. Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin-sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration of gliadin. Our results indicate that small intestine pathology can be induced in mice by intraluminal administration of poly I:C and that this is exacerbated by subsequent oral delivery of a relevant dietary antigen.

  5. Cannabinoid disposition in oral fluid after controlled smoked, vaporized, and oral cannabis administration.

    PubMed

    Swortwood, Madeleine J; Newmeyer, Matthew N; Andersson, Maria; Abulseoud, Osama A; Scheidweiler, Karl B; Huestis, Marilyn A

    2017-06-01

    Oral fluid (OF) is an important matrix for monitoring drugs. Smoking cannabis is common, but vaporization and edible consumption also are popular. OF pharmacokinetics are available for controlled smoked cannabis, but few data exist for vaporized and oral routes. Frequent and occasional cannabis smokers were recruited as participants for four dosing sessions including one active (6.9% Δ 9 -tetrahydrocannabinol, THC) or placebo cannabis-containing brownie, followed by one active or placebo cigarette, or one active or placebo vaporized cannabis dose. Only one active dose was administered per session. OF was collected before and up to 54 (occasional) or 72 (frequent) h after dosing from cannabis smokers. THC, 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), tetrahydrocannabivarin (THCV), cannabidiol (CBD), and cannabigerol (CBG) were quantified by liquid chromatography-tandem mass spectrometry. OF cannabinoid C max occurred during or immediately after cannabis consumption due to oral mucosa contamination. Significantly greater THC C max and significantly later THCV, CBD, and CBG t last were observed after smoked and vaporized cannabis compared to oral cannabis in frequent smokers only. No significant differences in THC, 11-OH-THC, THCV, CBD, or CBG t max between routes were observed for either group. For occasional smokers, more 11-OH-THC and THCCOOH-positive specimens were observed after oral dosing than after inhaled routes, increasing % positive cannabinoid results and widening metabolite detection windows after oral cannabis consumption. Utilizing 0.3 µg/L THCV and CBG cut-offs resulted in detection windows indicative of recent cannabis intake. OF pharmacokinetics after high potency CBD cannabis are not yet available precluding its use currently as a marker of recent use. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Published 2016. This article is a U.S. Government work and is in the public domain in

  6. Rapid absorption of diclofenac and acetaminophen after their oral administration to cattle.

    PubMed

    Sawaguchi, Akiyo; Sasaki, Kazuaki; Miyanaga, Keisuke; Nakayama, Mitsuhiro; Nagasue, Masato; Shimoda, Minoru

    2016-10-01

    The oral pharmacokinetics of diclofenac (DF) were evaluated in cattle by analyzing plasma concentration-time data after its intravenous and oral administration in order to propose the oral administration of DF as effective route to avoid long withdraw period. DF was intravenously and orally administered at 1 mg/kg to cattle using a crossover design with a 4-week washout period. Plasma concentrations of DF were determined by a HPLC analysis. The mean absorption time (MAT) and absorption half-life (t 1/2ka ) were 1.61 ± 0.61 and 1.51 ± 0.38 hr, respectively, and bioavailability was nearly 100%. The oral pharmacokinetics of acetaminophen (AAP) were also evaluated in cattle. Plasma concentrations of AAP were determined by a HPLC analysis. MAT and t 1/2ka were 2.85 ± 0.93 and 1.53 ± 0.28 hr, respectively, and bioavailability was approximately 70%. In conclusion, the results of the present study indicate that DF and AAP are rapidly absorbed from the forestomach of cattle. Therefore, the appropriate efficacies of these drugs may be achieved via their oral administration, even in cattle.

  7. Rapid absorption of diclofenac and acetaminophen after their oral administration to cattle

    PubMed Central

    SAWAGUCHI, Akiyo; SASAKI, Kazuaki; MIYANAGA, Keisuke; NAKAYAMA, Mitsuhiro; NAGASUE, Masato; SHIMODA, Minoru

    2016-01-01

    The oral pharmacokinetics of diclofenac (DF) were evaluated in cattle by analyzing plasma concentration-time data after its intravenous and oral administration in order to propose the oral administration of DF as effective route to avoid long withdraw period. DF was intravenously and orally administered at 1 mg/kg to cattle using a crossover design with a 4-week washout period. Plasma concentrations of DF were determined by a HPLC analysis. The mean absorption time (MAT) and absorption half-life (t1/2ka) were 1.61 ± 0.61 and 1.51 ± 0.38 hr, respectively, and bioavailability was nearly 100%. The oral pharmacokinetics of acetaminophen (AAP) were also evaluated in cattle. Plasma concentrations of AAP were determined by a HPLC analysis. MAT and t1/2ka were 2.85 ± 0.93 and 1.53 ± 0.28 hr, respectively, and bioavailability was approximately 70%. In conclusion, the results of the present study indicate that DF and AAP are rapidly absorbed from the forestomach of cattle. Therefore, the appropriate efficacies of these drugs may be achieved via their oral administration, even in cattle. PMID:27320817

  8. A pilot study on the serum pharmacokinetics of nattokinase in humans following a single, oral, daily dose.

    PubMed

    Ero, Michael Penfield; Ng, Connie M; Mihailovski, Tamara; Harvey, Nathaniel R; Lewis, Brad Howard

    2013-01-01

    Nattokinase is a serine protease and is derived from natto, a traditional Japanese, fermented, soybean food meal. Multiple authors have described the significant fibrinolytic, antithrombotic, and antihypertensive effects of natto. Nattokinase has been growing in popularity for use as a dietary supplement for the benefit of cardiovascular health. Little is known regarding the pharmacokinetic and pharmacodynamic properties of this enzyme, and the bioavailability of nattokinase is currently unknown. This study intended to (1) detect nattokinase directly and immunologically, (2) show that nattokinase and/or its metabolites were detectable in human blood following ingestion of a commercial preparation, and (3) chart a pharmacokinetic dosing effect for nattokinase. The research team designed the pilot study as an in vivo, human clinical trial. Healthy human subjects responded to an advertisement and were screened. Subjects who satisfied both inclusion and exclusion criteria were enrolled into the study. Subjects were then instructed to orally ingest a single capsule containing a known concentration of nattokinase immediately following a baseline blood draw. Subsequent blood draws occurred over a 24-h period. This study was conducted in Oakland, California, at a clinical reference laboratory and was performed with the approval of an institutional review board (IRB) to ensure that appropriate ethical standards were met. Eleven healthy participants (five male, six female, ages 21-65), who met eligibility criteria, were enrolled. Administration of nattokinase occurred orally with the ingestion of a single daily dose (2000 FU) of nattokinase. Capsules, each containing approximately 100 mg of nattokinase, in softgel form (NSK-SD, Japan Bio Science Laboratory, Osaka, Japan), were used in the study. Baseline blood samples were collected, and participants were observed swallowing a single capsule of the nattokinase supplement before returning at 2, 4, 8, 12, 24, and 48 h post

  9. Comparison of oral versus rectal administration of acetaminophen with codeine in postoperative pediatric adenotonsillectomy patients.

    PubMed

    Owczarzak, Vicki; Haddad, Joseph

    2006-08-01

    To examine whether acetaminophen with codeine administered per rectum is an effective alternative for pain control compared with oral administration after an adenotonsillectomy. A prospective, randomized control study. Seventy-five children aged 1 to 5 were recruited for this study. Each child was assigned randomly to receive either rectal or oral postoperative pain medication. A journal with eight questions was kept for 10 days after the operation, and an overall survey of five questions was filled out at the first postoperative visit. Postoperative pain was adequately controlled in those patients receiving suppositories when compared with those patients receiving oral pain medication. Adverse effects and total number of doses given per day were similar. Parents found the suppositories easy to administer, and more parents would switch or consider switching from oral pain medication to suppositories if given the choice. The suppositories achieved equivalent pain control as oral medication with few side effects and good tolerance. Furthermore, many parents preferred the suppositories to oral medication in maintaining postoperative pain control because of ease of administration. If given the choice for future surgeries, many parents would switch or consider switching from oral pain medication to suppositories.

  10. Administration of tauroursodeoxycholic acid prevents endothelial dysfunction caused by an oral glucose load

    PubMed Central

    Walsh, Lauren K.; Restaino, Robert M.; Neuringer, Martha; Manrique, Camila; Padilla, Jaume

    2017-01-01

    Postprandial hyperglycemia leads to a transient impairment in endothelial function; however, the mechanisms remain largely unknown. Previous work in cell culture models demonstrate that high glucose results in endoplasmic reticulum (ER) stress and, in animal studies, ER stress has been implicated as a cause of endothelial dysfunction. Herein we tested the hypothesis that acute oral administration of tauroursodeoxycholic acid (TUDCA, 1500mg), a chemical chaperone known to alleviate ER stress, would prevent hyperglycemia-induced endothelial dysfunction. In 12 young healthy subjects (seven men, five women), brachial artery flow-mediated dilation (FMD) was assessed at baseline, 1 hour, and 2 hours post an oral glucose challenge. Subjects were tested on two separate visits in a single-blind randomized crossover design: after oral ingestion of TUDCA or placebo capsules. FMD was reduced from baseline during hyperglycemia under the placebo condition (−32% at 1 hr and −28% at 2 hr post oral glucose load; p<0.05 from baseline) but not under the TUDCA condition (−4% at 1 hr and +0.3% at 2 hr post oral glucose load; p>0.05 from baseline). Postprandial plasma glucose and insulin were not altered by TUDCA ingestion. Plasma oxidative stress markers 3-nitrotyrosine and TBARs remained unaltered throughout the oral glucose challenge in both conditions. These results suggest that hyperglycemia-induced endothelial dysfunction can be mitigated by oral administration of TUDCA, thus supporting the hypothesis that ER stress may contribute to endothelial dysfunction during postprandial hyperglycemia. PMID:27503949

  11. Nursing Administrators' Views on Oral Health in Long-Term Care Facilities: An exploratory study.

    PubMed

    Urata, Janelle Y; Couch, Elizabeth T; Walsh, Margaret M; Rowe, Dorothy J

    2018-04-01

    Purpose: To explore the knowledge, attitudes, and practices of supervising nurse administrators (SNAs) regarding the oral care provided to long-term care facility (LTCF) residents and the role of dental professionals in those facilities. Methods: The investigators of this study partnered with the National Association of Nursing Administrators to send this cross-sectional study consisting of a 35-item electronic survey to its members whose email addresses were in their database. Online software tabulated responses and calculated frequencies (percentages) of responses for each survey item. Results: Of the 2,359 potential participants, 171 (n=171) completed the survey for a 7% response rate. Only 25% of the respondents were familiar with the expertise of dental hygienists (DHs), however once informed, the majority were interested in having DHs perform oral health staff trainings, oral screenings, and dental referrals and initiate fluoride varnish programs. Most respondents correctly answered the oral health-related knowledge items, understood that oral health is important to general health, but reported that the LTCF residents' oral health was only "good" or "fair." Fewer than half, (48%) of the SNAs were "very satisfied" with the quality of oral care provided to the residents. While more than half reported that they had no dentist on staff or on-site dental equipment, 77% reported that they would consider on-site mobile oral care services. Oral health training for staff was provided primarily by registered nurses, however only 32% reported including identification of dental caries as part of the in-service training. Conclusion: This exploratory study lays the foundation for more extensive research investigating various strategies to improve the oral health of LTCF residents, including increased collaboration between DHs and SNAs. Copyright © 2018 The American Dental Hygienists’ Association.

  12. Urinary profile of methylprednisolone and its metabolites after oral and topical administrations.

    PubMed

    Matabosch, Xavier; Pozo, Oscar J; Monfort, Núria; Pérez-Mañá, Clara; Farré, Magi; Marcos, Josep; Segura, Jordi; Ventura, Rosa

    2013-11-01

    Methylprednisolone (MP) is prohibited in sports competitions when administered by systemic routes; however its use by topical administration is allowed. Therefore, analytical approaches to distinguish between these different administration pathways are required. A reporting level of 30ng/mL was established for this purpose. However, the suitability of that reporting level for MP is not known. In the present work, excretion profiles of MP and different metabolites after oral and topical administrations have been compared. A method for the quantification of MP and the qualitative detection of fifteen previously reported metabolites has been validated. The method involved an enzymatic hydrolysis, liquid-liquid extraction and analysis by liquid chromatography coupled to tandem mass spectrometry. The method was found to be linear, selective, precise and accurate. The high sensitivity (limit of detection 0.1ng/mL) and linear range (0.1-250ng/mL) achieved allowed for the quantification of MP at both the low concentrations present after topical administration and the high concentrations detected after oral intake. The method was applied to samples collected after oral (4 or 40mg) and topical administration (10mg of MP aceponate/day for 5 consecutive days) to healthy volunteers. After oral administration, MP and all metabolites were detected in urines collected up to at least 36h. Only MP and five metabolites were detected in samples obtained after topical treatment. As expected, concentrations of MP after topical administration were well below current reporting level (30ng/mL), however 3 out of 4 samples in range 8-24h after the low oral dose (4mg) were also below that concentration. Taking into account metabolites detected after both administration routes, metabolites 16β,17α,21-trihydroxy-6α-methylpregna-1,4-diene-3,11,20-trione (M8) and 17α,20α,21-trihydroxy-6α-methylpregna-1,4-diene-3,11-dione (M11) are best markers to differentiate between topical and oral

  13. Reducing Tumour Hypoxia via Oral Administration of Oxygen Nanobubbles

    PubMed Central

    Owen, Joshua; McEwan, Conor; Nesbitt, Heather; Bovornchutichai, Phurit; Averre, Raymond; Borden, Mark; McHale, Anthony P.; Callan, John F.

    2016-01-01

    Hypoxia has been shown to be a key factor inhibiting the successful treatment of solid tumours. Existing strategies for reducing hypoxia, however, have shown limited efficacy and/or adverse side effects. The aim of this study was to investigate the potential for reducing tumour hypoxia using an orally delivered suspension of surfactant-stabilised oxygen nanobubbles. Experiments were carried out in a mouse xenograft tumour model for human pancreatic cancer (BxPc-3 cells in male SCID mice). A single dose of 100 μL of oxygen saturated water, oxygen nanobubbles or argon nanobubbles was administered via gavage. Animals were sacrificed 30 minutes post-treatment (3 per group) and expression of hypoxia-inducible-factor-1α (HIF1α) protein measured by real time quantitative polymerase chain reaction and Western blot analysis of the excised tumour tissue. Neither the oxygen saturated water nor argon nanobubbles produced a statistically significant change in HIF1α expression at the transcriptional level. In contrast, a reduction of 75% and 25% in the transcriptional and translational expression of HIF1α respectively (p<0.001) was found for the animals receiving the oxygen nanobubbles. This magnitude of reduction has been shown in previous studies to be commensurate with an improvement in outcome with both radiation and drug-based treatments. In addition, there was a significant reduction in the expression of vascular endothelial growth factor (VEGF) in this group and corresponding increase in the expression of arrest-defective protein 1 homolog A (ARD1A). PMID:28036332

  14. Reducing Tumour Hypoxia via Oral Administration of Oxygen Nanobubbles.

    PubMed

    Owen, Joshua; McEwan, Conor; Nesbitt, Heather; Bovornchutichai, Phurit; Averre, Raymond; Borden, Mark; McHale, Anthony P; Callan, John F; Stride, Eleanor

    2016-01-01

    Hypoxia has been shown to be a key factor inhibiting the successful treatment of solid tumours. Existing strategies for reducing hypoxia, however, have shown limited efficacy and/or adverse side effects. The aim of this study was to investigate the potential for reducing tumour hypoxia using an orally delivered suspension of surfactant-stabilised oxygen nanobubbles. Experiments were carried out in a mouse xenograft tumour model for human pancreatic cancer (BxPc-3 cells in male SCID mice). A single dose of 100 μL of oxygen saturated water, oxygen nanobubbles or argon nanobubbles was administered via gavage. Animals were sacrificed 30 minutes post-treatment (3 per group) and expression of hypoxia-inducible-factor-1α (HIF1α) protein measured by real time quantitative polymerase chain reaction and Western blot analysis of the excised tumour tissue. Neither the oxygen saturated water nor argon nanobubbles produced a statistically significant change in HIF1α expression at the transcriptional level. In contrast, a reduction of 75% and 25% in the transcriptional and translational expression of HIF1α respectively (p<0.001) was found for the animals receiving the oxygen nanobubbles. This magnitude of reduction has been shown in previous studies to be commensurate with an improvement in outcome with both radiation and drug-based treatments. In addition, there was a significant reduction in the expression of vascular endothelial growth factor (VEGF) in this group and corresponding increase in the expression of arrest-defective protein 1 homolog A (ARD1A).

  15. Effects of short-term oral administration of propranolol on tear secretion in clinically normal dogs

    PubMed Central

    Ghaffari, Masoud Selk; Arzani, Vahid; Khorami, Nargess; Rajaei, Seyed Mehdi

    2011-01-01

    This study evaluated the effects of short-term oral administration of propranolol on tear secretion in 15 clinically normal crossbreed dogs. The treatment group (n = 8) received propranolol (2 mg/kg q8h) orally for 7 days. The control group (n = 7) received placebo during the study. Schirmer I tear tests were performed on both eyes 1 d prior to drug administration (T0), at 1 (T1), 3 (T3), and 7 (T7) days of treatment. Tear production in dogs, measured by STT, was not significantly reduced in both groups. PMID:22294794

  16. Proline-containing dipeptide GVS-111 retains nootropic activity after oral administration.

    PubMed

    Ostrovskaya, R U; Mirsoev, T K; Romanova, G A; Gudasheva, T A; Kravchenko, E V; Trofimov, C C; Voronina, T A; Seredenin, S B

    2001-10-01

    Experiments on rats trained passive avoidance task showed that N-phenyl-acetyl-L-prolyl-glycyl ethyl ester, peptide analog of piracetam (GVS-111, Noopept) after oral administration retained antiamnesic activity previously observed after its parenteral administration. Effective doses were 0.5-10 mg/kg. Experiments on a specially-developed model of active avoidance (massive one-session learning schedule) showed that GVS-111 stimulated one-session learning after single administration, while after repeated administration it increased the number of successful learners among those animals who failed after initial training. In this respect, GVS-111 principally differs from its main metabolite cycloprolylglycine and standard nootropic piracetam.

  17. Pharmacokinetics of voriconazole after oral administration of single and multiple doses in African grey parrots (Psittacus erithacus timneh).

    PubMed

    Flammer, Keven; Nettifee Osborne, Julie A; Webb, Donna J; Foster, Laura E; Dillard, Stacy L; Davis, Jennifer L

    2008-01-01

    To determine the pharmacokinetics and safety of orally administered voriconazole in African grey parrots. 20 clinically normal Timneh African grey parrots (Psittacus erithacus timneh). In single-dose trials, 12 parrots were each administered 6, 12, and 18 mg of voriconazole/kg orally and plasma concentrations of voriconazole were determined via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) was administered orally to 6 birds every 12 hours for 9 days; a control group (2 birds) received tap water. Treatment effects were assessed via observation, clinicopathologic analyses (3 assessments), and measurement of trough plasma voriconazole concentrations (2 assessments). Voriconazole's elimination half-life was short (1.1 to 1.6 hours). Higher doses resulted in disproportional increases in the maximum plasma voriconazole concentration and area under the curve. Trough plasma voriconazole concentrations achieved in the multiple-dose trial were lower than those achieved after administration of single doses. Polyuria (the only adverse treatment effect) developed in treated and control birds but was more severe in the treatment group. In African grey parrots, voriconazole has dose-dependent pharmacokinetics and may induce its own metabolism. Oral administration of 12 to 18 mg of voriconazole/kg twice daily is a rational starting dose for treatment of African grey parrots infected with Aspergillus or other fungal organisms that have a minimal inhibitory concentration for voriconazole < or = 0.4 microg/mL. Higher doses may be needed to maintain plasma voriconazole concentrations during long-term treatment. Safety and efficacy of various voriconazole treatment regimens in this species require investigation.

  18. Altered metabolism of orally administered loxoprofen in human subjects after an oral administration of loxoprofen for three consecutive days followed by a seven-day washout.

    PubMed

    Kim, In-Wha; Chung, Suk-Jae; Shim, Chang-Koo

    2002-04-01

    The effect of pretreatment (i.e., oral administration of loxoprofen for 3 consecutive days followed by a 7-day washout) on the pharmacokinetics and metabolism of the drug was studied in humans. In a control study, a Loxonin tablet (60 mg as loxoprofen anhydrous) was administered orally to 6 healthy male Korean subjects. In a pretreatment study, a Loxonin tablet was administered orally to the subjects once daily for 3 consecutive days. On the 10(th) day, a Loxonin tablet was administered orally to the subjects, and the concentrations of loxoprofen and the trans- and cis-alcohol metabolites in the plasma and urine were measured as a function of time. Using this pretreatment, the area under the curve (AUC) of the trans-alcohol metabolite of loxoprofen in the plasma, but not those of loxoprofen and the cis-alcohol metabolite, was increased (1.5-fold, p < 0.05), leading to increased contribution of the trans-alcohol metabolite to the total urinary recovery of loxoprofen (1.3-fold, p < 0.05). The urinary recovery of total metabolites, which was largely (> 90%) comprised of conjugate metabolites, was also increased as a result of the pretreatment (1.5-fold, p < 0.05). These results indicate that stereoselective reduction to trans-alcohol metabolites as well as the phase II metabolism of loxoprofen may be increased by such a pretreatment in human subjects. Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:973-979, 2002

  19. Metabolomic Analysis of Blood Plasma after Oral Administration of N-acetyl-d-Glucosamine in Dogs

    PubMed Central

    Osaki, Tomohiro; Kurozumi, Seiji; Sato, Kimihiko; Terashi, Taro; Azuma, Kazuo; Murahata, Yusuke; Tsuka, Takeshi; Ito, Norihiko; Imagawa, Tomohiro; Minami, Saburo; Okamoto, Yoshiharu

    2015-01-01

    N-acetyl-d-glucosamine (GlcNAc) is a monosaccharide that polymerizes linearly through (1,4)-β-linkages. GlcNAc is the monomeric unit of the polymer chitin. GlcNAc is a basic component of hyaluronic acid and keratin sulfate found on the cell surface. The aim of this study was to examine amino acid metabolism after oral GlcNAc administration in dogs. Results showed that plasma levels of ectoine were significantly higher after oral administration of GlcNAc than prior to administration (p < 0.001). To our knowledge, there have been no reports of increased ectoine concentrations in the plasma. The mechanism by which GlcNAc administration leads to increased ectoine plasma concentration remains unclear; future studies are required to clarify this mechanism. PMID:26262626

  20. Cerebrospinal fluid abacavir concentrations in HIV-positive patients following once-daily administration.

    PubMed

    Calcagno, A; Pinnetti, C; De Nicolò, A; Scarvaglieri, E; Gisslen, M; Tempestilli, M; D'Avolio, A; Fedele, V; Di Perri, G; Antinori, A; Bonora, S

    2018-06-01

    Abacavir is a widely used nucleotide reverse transcriptase inhibitor, for which cerebrospinal fluid (CSF) exposure has been previously assessed in twice-daily recipients. We studied abacavir CSF concentrations in 61 and nine HIV-positive patients taking abacavir once daily and twice daily, respectively. Patients on once-daily abacavir had higher plasma and CSF concentrations (96 vs. 22 ng ml -1 , P = 0.038 and 123 vs. 49 ng ml -1 , P = 0.038) but similar CSF-to-plasma ratios (0.8 vs. 0.5, P = 0.500). CSF abacavir concentrations were adequate in patients receiving once-daily treatment. © 2018 The British Pharmacological Society.

  1. Pharmacokinetics and selected pharmacodynamics of trazodone following intravenous and oral administration to horses undergoing fitness training.

    PubMed

    Knych, Heather K; Mama, Khursheed R; Steffey, Eugene P; Stanley, Scott D; Kass, Philip H

    2017-10-01

    OBJECTIVE To measure concentrations of trazodone and its major metabolite in plasma and urine after administration to healthy horses and concurrently assess selected physiologic and behavioral effects of the drug. ANIMALS 11 Thoroughbred horses enrolled in a fitness training program. PROCEDURES In a pilot investigation, 4 horses received trazodone IV (n = 2) or orally (2) to select a dose for the full study; 1 horse received a vehicle control treatment IV. For the full study, trazodone was initially administered IV (1.5 mg/kg) to 6 horses and subsequently given orally (4 mg/kg), with a 5-week washout period between treatments. Blood and urine samples were collected prior to drug administration and at multiple time points up to 48 hours afterward. Samples were analyzed for trazodone and metabolite concentrations, and pharmacokinetic parameters were determined; plasma drug concentrations following IV administration best fit a 3-compartment model. Behavioral and physiologic effects were assessed. RESULTS After IV administration, total clearance of trazodone was 6.85 ± 2.80 mL/min/kg, volume of distribution at steady state was 1.06 ± 0.07 L/kg, and elimination half-life was 8.58 ± 1.88 hours. Terminal phase half-life was 7.11 ± 1.70 hours after oral administration. Horses had signs of aggression and excitation, tremors, and ataxia at the highest IV dose (2 mg/kg) in the pilot investigation. After IV drug administration in the full study (1.5 mg/kg), horses were ataxic and had tremors; sedation was evident after oral administration. CONCLUSIONS AND CLINICAL RELEVANCE Administration of trazodone to horses elicited a wide range of effects. Additional study is warranted before clinical use of trazodone in horses can be recommended.

  2. Safety of fluralaner, a novel systemic antiparasitic drug, in MDR1(-/-) Collies after oral administration

    PubMed Central

    2014-01-01

    Background Fluralaner is a novel systemic ectoparasiticide for dogs providing long-acting flea- and tick-control after a single oral dose. This study investigated the safety of oral administration of fluralaner at 3 times the highest expected clinical dose to Multi Drug Resistance Protein 1 (MDR1(-/-)) gene defect Collies. Methods Sixteen Collies homozygous for the MDR1 deletion mutation were included in the study. Eight Collies received fluralaner chewable tablets once at a dose of 168 mg/kg; eight sham dosed Collies served as controls. All Collies were clinically observed until 28 days following treatment. Results No adverse events were observed subsequent to fluralaner treatment of MDR1(-/-) Collies at three times the highest expected clinical dose. Conclusions Fluralaner chewable tablets are well tolerated in MDR1(-/-) Collies following oral administration. PMID:24602342

  3. [Effect of Radix euphorbiae pekinensis extract on bioavailability of paclitaxel after their oral co-administration].

    PubMed

    Li, Minghua; Peng, Li; Yang, Fuheng; Liu, Sijia; Wang, Shengqi

    2015-06-01

    To evaluate the effect of Radix euphorbiae pekinensis extract on the permeability and bioavailability of paclitaxel co-administered orally. Based on Ussing Chamber and in vivo experiment, the permeability and bioavailability of paclitaxel were evaluated after oral co-administration with radix euphorbiae pekinensis in rats. The contents of paclitaxel in the permeates and the blood samples were determined using HPLC and LC-MS/MS method, respectively. In Radix euphorbiae pekinensis co-administration group, the Papp of the mucosal-to-serosal (M-S) transport or serosal-to-mucosal transport (S-M) of paclitaxel in the jejunum or ileum segment differed significantly from those in verapamil co-administration group and blank control group (P<0.05), but the Papp of S-M transport in the colon showed no significant difference from that in the blank control group. In the blank group, the average absolute bioavailability (AB%) of orally administered paclitaxel was only 2.81%, compared to that of 7.63% in radix euphorbiae pekinensis group. The average AB% in verapamil group was about 1.5 times that of the blank group. Co-administration of Radix euphorbiae pekinensis extract can increase the bioavailability of orally administered paclitaxel.

  4. COMPARATIVE METABOLISM OF ARSENIC IN MICE AFTER A SINGLE OR REPEATED ORAL ADMINISTRATION OF ARSENATE

    EPA Science Inventory

    COMPARATIVE METABOLISM OF ARSENIC IN MICE AFTER A SINGLE OR REPEATED ORAL ADMINISTRATION OF ARSENATE
    Michael F. Hughes*1, Elaina M. Kenyon1, Brenda C. Edwards1, Carol T. Mitchell1, Luz Maria Del Razo2 and David J. Thomas1
    1US EPA, ORD, NHEERL, ETD, PKB, Research Triangle Pa...

  5. TISSUE DISPOSITION OF DIMETHYLARSINIC ACID IN THE MOUSE AFTER ACUTE ORAL ADMINISTRATION

    EPA Science Inventory

    TISSUE DISPOSITION OF DIMETHYLARSINIC ACID IN THE MOUSE
    AFTER ACUTE ORAL ADMINISTRATION

    Michael F. Hughes, Ph.D., Brenda C. Edwards, Carol T. Mitchell and Elaina M. Kenyon, Ph.D. United States Environmental Protection Agency, Office of Research and Development, Nation...

  6. TISSUE DOSIMETRY, METABOLISM AND EXCRETION OF PENTAVALENT AND TRIVALENT DIMETHYLATED ARSENIC IN MICE AFTER ORAL ADMINISTRATION

    EPA Science Inventory

    Dimethylarsinic acid (DMA(V)) is a rat bladder carcinogen and the major urinary metabolite of inorganic arsenic in most mammals. This study examined the disposition of pentavalent and trivalent dimethylated arsenic in mice after acute oral administration. Adult female mice were...

  7. Oral Medications: Proper Use and Administration. Book 1, Bosnian and Russian. Book 2, Nuer and Spanish.

    ERIC Educational Resources Information Center

    Anoka County Community Health and Environmental Services, Coon Rapids, MN.

    These two guides provide information in English, Bosnian, Russian, Nuer, and Spanish on the proper use and administration of oral medications. Topics covered include the reasons for taking medication, information on the prescription label, following special instructions, asking questions of the pharmacist, safe storage of medicine, child-proof…

  8. Oral impacts on daily performances in white-collar port workers in Nellore, India - a cross-sectional study.

    PubMed

    Soundarya Chowdary, Mandava; Sudhir, Kudlur Maheswarappa; Reddy, Vuyurru Chandrasekhara; Krishna Kumar, Rachakorda Veera Venkata Sathya Sai; Srinivasulu, Gomasani

    2016-01-01

    Oral diseases not only cause pain, but severely impair large number of individuals and can affect various aspects of life, including oral functions, appearance and interpersonal relationships. The aim of the study was to assess the interrelationship between oral impact on daily performance (OIDP) scores, socio-demographic characteristics, dental caries experience and periodontal status. A cross-sectional descriptive epidemiological study was conducted on a sample of 250 white-collar port workers who were willing to participate. OIDP was assessed using pre-validated questionnaire. Oral health status was assessed using modified World Health Organisation (1997) Proforma. Test of association was conducted between the OIDP score, socio-demographic variables, and periodontal status; loss of attachment was determined by using chi-square statistics and Mann-Whitney test. Logistic regression was performed to identify significant predictors of OIDP scores by inputting clinical oral examination variables into the equation, stepwise. A total of 250 white-collar workers in the port participated in the study with mean age of 34.67 ± 6.36. Among them, 219 were males and 31 were females. The OIDP items most commonly affected by oral health status were eating and enjoying food (48.4%), cleaning teeth (48%), sleeping and relaxing (44.4%).There was statistically significant relationship between missing teeth in the decayed missing filled teeth component and OIDP score (p < 0.001). The participants with caries have a greater odd (2.11) of having OIDP score ≥ 1 than those without caries. The participants with missing teeth have a greater odd (3.60) of having OIDP score ≥ 1. The participants in the age group of 31-40 years had a greater odd (2.80) of having OIDP score ≥ 1. Oral health had an impact on the quality of life of white-collar workers in the port. Physical functions of teeth like eating and cleaning of teeth, sleeping and relaxing were more affected.

  9. Effects of oral and intravenous administration of buspirone on food-cocaine choice in socially housed male cynomolgus monkeys.

    PubMed

    Czoty, Paul W; Nader, Michael A

    2015-03-13

    Drugs acting at D3 dopamine receptors have been suggested as medications for cocaine dependence. These experiments examined the effects of intravenously and orally administered buspirone, a D2-like receptor antagonist with high affinity for D3 and D4 receptors, on the relative reinforcing strength of cocaine in group-housed male cynomolgus monkeys. Use of socially housed monkeys permitted the assessment of whether social status, known to influence D2-like receptor availability, modulates the behavioral effects of buspirone. Buspirone was administered acutely to monkeys self-administering cocaine under a food-drug choice procedure in which a cocaine self-administration dose-effect curve was determined daily. When administered by either route, buspirone significantly decreased cocaine choice in dominant-ranked monkeys. In subordinate monkeys, however, i.v. buspirone was ineffective on average, and oral buspirone increased choice of lower cocaine doses. The effects of buspirone only differed according to route of administration in subordinate monkeys. Moreover, it is noteworthy that the effects of buspirone were similar to those of the D3 receptor-selective antagonist PG01037 and qualitatively different than those of less selective drugs that act at D2-like or serotonin (5-HT)1A receptors, suggesting a D3 and possibly D4 receptor mechanism of action for buspirone. Taken together, the data support the utility of drugs targeting D3/D4 receptors as potential treatments for cocaine addiction, particularly in combination with enriching environmental manipulations.

  10. Oral fluid/plasma cannabinoid ratios following controlled oral THC and smoked cannabis administration.

    PubMed

    Lee, Dayong; Vandrey, Ryan; Milman, Garry; Bergamaschi, Mateus; Mendu, Damodara R; Murray, Jeannie A; Barnes, Allan J; Huestis, Marilyn A

    2013-09-01

    Oral fluid (OF) is a valuable biological alternative for clinical and forensic drug testing. Evaluating OF to plasma (OF/P) cannabinoid ratios provides important pharmacokinetic data on the disposition of drug and factors influencing partition between matrices. Eleven chronic cannabis smokers resided on a closed research unit for 51 days. There were four 5-day sessions of 0, 30, 60, and 120 mg oral ∆(9)-tetrahydrocannabinol (THC)/day followed by a five-puff smoked cannabis challenge on Day 5. Each session was separated by 9 days ad libitum cannabis smoking. OF and plasma specimens were analyzed for THC and metabolites. During ad libitum smoking, OF/P THC ratios were high (median, 6.1; range, 0.2-348.5) within 1 h after last smoking, decreasing to 0.1-20.7 (median, 2.1) by 13.0-17.1 h. OF/P THC ratios also decreased during 5-days oral THC dosing, and after the smoked cannabis challenge, median OF/P THC ratios decreased from 1.4 to 5.5 (0.04-245.6) at 0.25 h to 0.12 to 0.17 (0.04-5.1) at 10.5 h post-smoking. In other studies, longer exposure to more potent cannabis smoke and oromucosal cannabis spray was associated with increased OF/P THC peak ratios. Median OF/P 11-nor-9-carboxy-THC (THCCOOH) ratios were 0.3-2.5 (range, 0.1-14.7) ng/μg, much more consistent in various dosing conditions over time. OF/P THC, but not THCCOOH, ratios were significantly influenced by oral cavity contamination after smoking or oromucosal spray of cannabinoid products, followed by time-dependent decreases. Establishing relationships between OF and plasma cannabinoid concentrations is essential for making inferences of impairment or other clinical outcomes from OF concentrations.

  11. Oral fluid/plasma cannabinoid ratios following controlled oral THC and smoked cannabis administration

    PubMed Central

    Lee, Dayong; Vandrey, Ryan; Milman, Garry; Bergamaschi, Mateus; Mendu, Damodara R.; Murray, Jeannie A.; Barnes, Allan J.; Huestis, Marilyn A.

    2013-01-01

    BACKGROUND Oral fluid (OF) is a valuable biological alternative for clinical and forensic drug testing. Evaluating OF to plasma (OF/P) cannabinoid ratios provides important pharmacokinetic data on the disposition of drug and factors influencing partition between matrices. METHODS Eleven chronic cannabis smokers resided on a closed research unit for 51 days. There were four 5-day sessions of 0, 30, 60, and 120 mg oral Δ9-tetrahydrocannabinol (THC)/per day followed by a 5-puff smoked cannabis challenge on Day 5. Each session was separated by 9 days ad-libitum cannabis smoking. OF and plasma specimens were analyzed for THC and metabolites. RESULTS During ad-libitum smoking, OF/P THC ratios were high (median 6.1, range 0.2– 348.5) within 1 h after last smoking, decreasing to 0.1–20.7 (median 2.1) by 13.0–17.1 h. OF/P THC ratios also decreased during 5-days oral THC dosing, and after the smoked cannabis challenge, median OF/P THC ratios decreased from 1.4–5.5 (0.04–245.6) at 0.25 h to 0.12–0.17 (0.04–5.1) at 10.5 h post smoking. In other studies, longer exposure to more potent cannabis smoke and oromucosal cannabis spray was associated with increased OF/P THC peak ratios. Median OF/P 11-nor-9-carboxy-THC (THCCOOH) ratios were 0.3–2.5 (range 0.1–14.7) ng/µg, much more consistent in various dosing conditions over time. CONCLUSIONS OF/P THC, but not THCCOOH, ratios were significantly influenced by oral cavity contamination after smoking or oromucosal spray of cannabinoid products, followed by time-dependent decreases. Establishing relationships between OF and plasma cannabinoid concentrations is essential for making inferences of impairment or other clinical outcomes from OF concentrations. PMID:23831756

  12. Serum and tissue concentrations of gallium after oral administration of gallium nitrate and gallium maltolate to neonatal calves.

    PubMed

    Monk, Caroline S; Sweeney, Raymond W; Bernstein, Lawrence R; Fecteau, Marie-Eve

    2016-02-01

    To determine serum and tissue concentrations of gallium (Ga) after oral administration of gallium nitrate (GaN) and gallium maltolate (GaM) to neonatal calves. 8 healthy neonatal calves. Calves were assigned to 1 of 2 groups (4 calves/group). Gallium (50 mg/kg) was administered as GaN or GaM (equivalent to 13.15 mg of Ga/kg for GaN and 7.85 mg of Ga/kg for GaM) by oral gavage once daily for 5 days. Blood samples were collected 0, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after Ga administration on day 1; 4 and 24 hours after Ga administration on days 2, 3, and 4; and 4, 12, and 24 hours after Ga administration on day 5. On day 6, calves were euthanized and tissue samples were obtained. Serum and tissue Ga concentrations were measured by use of mass spectrometry. Data were adjusted for total Ga dose, and comparisons were made between the 2 groups. Calves receiving GaM had a significantly higher dose-adjusted area under the curve and dose-adjusted maximum serum Ga concentration than did calves receiving GaN. Despite receiving less Ga per dose, calves receiving GaM had tissue Ga concentrations similar to those for calves receiving GaN. In this study, calves receiving GaM had significantly higher Ga absorption than did calves receiving GaN. These findings suggested that GaM might be useful as a prophylactic agent against Mycobacterium avium subsp paratuberculosis infection in neonatal calves.

  13. Evaluation of adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs.

    PubMed

    Luna, Stelio P L; Basílio, Ana C; Steagall, Paulo V M; Machado, Luciana P; Moutinho, Flávia Q; Takahira, Regina K; Brandão, Cláudia V S

    2007-03-01

    To evaluate adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs. 36 adult dogs. Values for CBC, urinalysis, serum biochemical urinalyses, and occult blood in feces were investigated before and 7, 30, 60, and 90 days after daily oral administration (n = 6 dogs/group) of lactose (1 mg/kg, control treatment), etodolac (15 mg/kg), meloxicam (0.1 mg/kg), carprofen (4 mg/kg), and ketoprofen (2 mg/kg for 4 days, followed by 1 mg/kg daily thereafter) or flunixin (1 mg/kg for 3 days, with 4-day intervals). Gastroscopy was performed before and after the end of treatment. For serum gamma-glutamyltransferase activity, values were significantly increased at day 30 in dogs treated with lactose, etodolac, and meloxicam within groups. Bleeding time was significantly increased in dogs treated with carprofen at 30 and 90 days, compared with baseline. At 7 days, bleeding time was significantly longer in dogs treated with meloxicam, ketoprofen, and flunixin, compared with control dogs. Clotting time increased significantly in all groups except those treated with etodolac. At day 90, clotting time was significantly shorter in flunixin-treated dogs, compared with lactose-treated dogs. Gastric lesions were detected in all dogs treated with etodolac, ketoprofen, and flunixin, and 1 of 6 treated with carprofen. Carprofen induced the lowest frequency of gastrointestinal adverse effects, followed by meloxicam. Monitoring for adverse effects should be considered when nonsteroidal anti-inflammatory drugs are used to treat dogs with chronic pain.

  14. Perspectives on oral pulmonary hypertension therapies recently approved by the U.S. Food and Drug Administration.

    PubMed

    Hill, Nicholas S; Badesch, David; Benza, Raymond L; D'Eletto, Thomas A; Farber, Harrison W; Gomberg-Maitland, Mardi; Hassoun, Paul M; Preston, Ioana

    2015-02-01

    In the past 18 months, the U.S. Food and Drug Administration approved macitentan, riociguat, and treprostinil as oral agents for the treatment of pulmonary arterial hypertension (PAH); riociguat also became the first agent approved for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). These new agents are welcome additional therapeutic options for PAH and CTEPH. However, their use can be complicated by potential drug interactions, adverse effects, dosing complexity, and cost. Macitentan, the newest endothelin receptor antagonist, showed significant benefits in a long-term event-driven trial of morbidity and mortality. Dosed once daily and with minimal liver toxicity, it has potential drug interactions with potent CYP 3A4 inhibitors and inducers, and can decrease hemoglobin levels. Riociguat is approved for PAH and clinically inoperable CTEPH to improve exercise capacity and functional status. Riociguat requires dose titration beginning with 1 mg up to 2.5 mg three times a day, as tolerated, and should be used with caution in patients with underlying risk factors for systemic hypotension. Oral treprostinil, approved to improve exercise capacity in PAH, is associated with gastrointestinal side effects and headaches that are often dose limiting. Doses can begin with 0.125 mg or 0.25 mg twice a day with gradual increases on up to a weekly basis, as tolerated. Thrice daily dosing and administration with a meal can improve tolerance. These newer agents represent advances, but their specific roles in relation to pre-existing therapies are undergoing further evaluation. Therefore, close collaboration with clinicians at centers with therapeutic expertise is highly recommended to optimize patient outcomes.

  15. Immunomodulation of Experimental Autoimmune Encephalomyelitis by Oral Administration of Copolymer 1

    NASA Astrophysics Data System (ADS)

    Teitelbaum, Dvora; Arnon, Ruth; Sela, Michael

    1999-03-01

    The activity of copolymer 1 (Cop 1, Copax-one, glatiramer acetate) in suppressing experimental autoimmune encephalomyelitis (EAE) and in the treatment of multiple sclerosis patients when injected parenterally has been extensively demonstrated. In the present study we addressed the question of whether Cop 1 can induce oral tolerance to EAE similar to myelin basic protein (MBP). We now have demonstrated that oral Cop 1 inhibited EAE induction in both rats and mice. Furthermore, oral Cop 1 was more effective than oral MBP in suppressing EAE in rats. The beneficial effect of oral Cop 1 was found to be associated with specific inhibition of the proliferative and Th1 cytokine secretion responses to MBP of spleen cells from Cop 1-fed mice and rats. In all of these assays, oral Cop 1 was more effective than oral MBP. The tolerance induced by Cop 1 could be adoptively transferred with spleen cells from Cop 1-fed animals. Furthermore, Cop 1-specific T cell lines, which inhibit EAE induction in vivo, could be isolated from the above spleen cells. These T cell lines secrete the anti-inflammatory cytokines IL-10 and transforming growth factor type β , but not IL-4, in response to both Cop 1 and MBP. In conclusion, oral Cop 1 has a beneficial effect on the development of EAE that is associated with down-regulation of T cell immune responses to MBP and is mediated by Th2/3 type regulatory cells. These results suggest that oral administration of Cop 1 may modulate multiple sclerosis as well.

  16. Oral anticoagulant dosing, administration, and storage: a cross-sectional survey of Canadian health care providers.

    PubMed

    Piran, Siavash; Schulman, Sam; Panju, Mohamed; Pai, Menaka

    2018-01-01

    Direct oral anticoagulant (DOAC) use is increasing worldwide. However, if not taken or prescribed correctly, DOACs have serious side effects. It is crucial that healthcare providers (HCPs) offer patients accurate information and counselling around DOACs, to optimize safe and effective use. To assess knowledge around oral anticoagulant indication, dosing, storage, and administration, an electronic survey was distributed to HCPs across Canada from June to August 2017, with 18 questions on the practical use of oral anticoagulants. A total of 191 responses were received: 100 from nurse practitioners, 42 from pharmacists, 27 from Hematologists, 5 from Thrombosis specialists, 4 from internists, 9 from residents and fellows, and 2 each from family physicians and registered nurses. Only 51 (26.7%) of the respondents correctly identified all the approved indications for warfarin and 4 DOACs. Only 101 (52.9%) correctly identified that DOACs are not approved for treatment of heparin-induced thrombocytopenia, cerebral sinus venous thrombosis, or mechanical prosthetic valves. 112 (58.6%) felt comfortable or very comfortable prescribing oral anticoagulants. Half of the respondents knew that dabigatran should not be crushed, however only 85 (44.5%) knew that it should not be exposed to moisture. 94 (49%) knew that higher dose rivaroxaban should be taken with food. The results of our study demonstrate that there are important knowledge gaps around HCPs' practical understanding of oral anticoagulants. Future research should focus on educational interventions to improve HCPs' knowledge around indications, dosing, storage, and administration, with the goal of enhancing patient safety.

  17. Oral administration of a recombinant cholera toxin B subunit promotes mucosal healing in the colon.

    PubMed

    Baldauf, K J; Royal, J M; Kouokam, J C; Haribabu, B; Jala, V R; Yaddanapudi, K; Hamorsky, K T; Dryden, G W; Matoba, N

    2017-07-01

    Cholera toxin B subunit (CTB) is a component of a licensed oral cholera vaccine. However, CTB has pleiotropic immunomodulatory effects whose impacts on the gut are not fully understood. Here, we found that oral administration in mice of a plant-made recombinant CTB (CTBp) significantly increased several immune cell populations in the colon lamina propria. Global gene expression analysis revealed that CTBp had more pronounced impacts on the colon than the small intestine, with significant activation of TGFβ-mediated pathways in the colon epithelium. The clinical relevance of CTBp-induced impacts on colonic mucosa was examined. In a human colon epithelial model using Caco2 cells, CTBp, but not the non-GM1-binding mutant G33D-CTBp, induced TGFβ-mediated wound healing. In a dextran sodium sulfate (DSS) acute colitis mouse model, oral administration of CTBp protected against colon mucosal damage as manifested by mitigated body weight loss, decreased histopathological scores, and blunted escalation of inflammatory cytokine levels while inducing wound healing-related genes. Furthermore, biweekly oral administration of CTBp significantly reduced disease severity and tumorigenesis in the azoxymethane/DSS model of ulcerative colitis and colon cancer. Altogether, these results demonstrate CTBp's ability to enhance mucosal healing in the colon, highlighting its potential application in ulcerative colitis therapy besides cholera vaccination.

  18. Effects of oral powder electrolyte administration on packed cell volume, plasma chemistry parameters, and incidence of colic in horses participating in a 6-day 162-km trail ride.

    PubMed

    Walker, Wade T; Callan, Robert J; Hill, Ashley E; Tisher, Kelly B

    2014-08-01

    This study evaluated the effects of administering oral powder electrolytes on packed cell volume (PCV), plasma chemistry parameters, and incidence of colic in horses participating on a 6-day 162-km trail ride in which water was not offered ad libitum. Twenty-three horses received grain with powder electrolytes daily while 19 control horses received grain only. Horses were ridden approximately 32 km a day at a walk or trot. Packed cell volume and plasma chemistry parameters were analyzed daily. Episodes of colic were diagnosed and treated by a veterinarian unaware of treatment group allocation. Blood parameters and incidence of colic were compared between treatment groups. Electrolyte administration did not alter PCV or plasma chemistry parameters compared to controls. The incidence of colic was significantly higher in treated horses (P = 0.05). Oral powder electrolytes did not enhance hydration status or electrolyte homeostasis and may be associated with colic in horses participating on long distance trail rides similar to this model.

  19. Oral temperatures of the elderly in nursing homes in summer and winter in relation to activities of daily living

    NASA Astrophysics Data System (ADS)

    Nakamura, K.; Tanaka, Masatoshi; Motohashi, Yutaka; Maeda, Akira

    This study was conducted to clarify the seasonal difference in body temperature in summer and winter, and to document the thermal environment of the elderly living in nursing homes. The subjects were 57 healthy elderly people aged >=63 years living in two nursing homes in Japan. One of the homes was characterized by subjects with low levels of activities of daily living (ADL). Oral temperatures were measured in the morning and afternoon, with simultaneous recording of ambient temperature and relative humidity. Oral temperatures in summer were higher than in winter, with statistically significant differences (P<0.05) of 0.25 (SD 0.61) °C in the morning and 0.24 (SD 0.50) °C in the afternoon. Differences between oral temperatures in summer and winter tended to be greater in subjects with low ADL scores, even when their room temperature was well-controlled. In conclusion, the oral temperatures of the elderly are lower in winter than summer, particularly in physically inactive people. It appears that those with low levels of ADL are more vulnerable to large changes in ambient temperature.

  20. Tolerance to effects of high-dose oral δ9-tetrahydrocannabinol and plasma cannabinoid concentrations in male daily cannabis smokers.

    PubMed

    Gorelick, David A; Goodwin, Robert S; Schwilke, Eugene; Schwope, David M; Darwin, William D; Kelly, Deanna L; McMahon, Robert P; Liu, Fang; Ortemann-Renon, Catherine; Bonnet, Denis; Huestis, Marilyn A

    2013-01-01

    Oral cannabinoids are taken for medicinal or recreational purposes, yet little is known about tolerance to their effects after high-dose extended exposure. The development of tolerance to effects of around-the-clock oral synthetic Δ9-tetrahydrocannabinol (THC) (20 mg every 3.5-6 h) was evaluated in 13 healthy male daily cannabis smokers residing on a secure research unit: 40 mg on Day 1; 100 mg on Days 2-4; 120 mg on Days 5-6. Systolic and diastolic blood pressure (BP), heart rate, and symptoms of subjective intoxication (100 mm visual-analogue scales, VAS) were assessed the morning of Day 1 (before any oral THC), and on Days 2, 4 and 6, every 30 min for 3 h after the first morning THC dose. Morning subjective intoxication ratings increased from Days 1 to 2, and then declined on Days 4 and 6. The morning THC dose increased intoxication ratings on Day 2, but had less effect on Days 4 and 6, a pattern consistent with tolerance. THC lowered BP and increased heart rate over the six days. Plasma THC and 11-OH-THC concentrations increased significantly over the first five days of dosing. Six days of around-the-clock, oral THC produced tolerance to subjective intoxication, but not to cardiovascular effects.

  1. Oral administration of Dictyostelium differentiation-inducing factor 1 lowers blood glucose levels in streptozotocin-induced diabetic rats.

    PubMed

    Kawaharada, Ritsuko; Nakamura, Akio; Takahashi, Katsunori; Kikuchi, Haruhisa; Oshima, Yoshiteru; Kubohara, Yuzuru

    2016-06-15

    Differentiation-inducing factor 1 (DIF-1), originally discovered in the cellular slime mold Dictyostelium discoideum, and its derivatives possess pharmacological activities, such as the promotion of glucose uptake in non-transformed mammalian cells in vitro. Accordingly, DIFs are considered promising lead candidates for novel anti-diabetic drugs. The aim of this study was to assess the anti-diabetic and toxic effects of DIF-1 in mouse 3T3-L1 fibroblast cells in vitro and in diabetic rats in vivo. Main methods We investigated the in vitro effects of DIF-1 and DIF-1(3M), a derivative of DIF-1, on glucose metabolism in 3T3-L1 cells by using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS). We also examined the effects of DIF-1 on blood glucose levels in streptozotocin (STZ)-induced rats. CE-TOF-MS revealed that 20μM DIF-1 and 20μM DIF-1(3M) promoted glucose uptake and metabolism in 3T3-L1 cells. Oral administration of DIF-1 (30mg/kg) significantly lowered basal blood glucose levels in STZ-treated rats and promoted a decrease in blood glucose levels after oral glucose loading (2.5g/kg) in the rats. In addition, daily oral administration of DIF-1 (30mg/kg/day) for 1wk significantly lowered the blood glucose levels in STZ-treated rats but did not affect their body weight and caused only minor alterations in the levels of other blood analytes. These results indicate that DIF-1 may be a good lead compound for the development of anti-diabetic drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. [Role of intraosteal administration of antibiotics in treatment of local oral mucinous carcinoma].

    PubMed

    Ivanov, V M; Ivanova, O V; Sheĭkin, M V

    2013-01-01

    The problems of prophylaxis of infectious complications in the treatment of oral local mucinous carcinoma are considered relevant to 204 respective cases. More favourable results of the combined and complex treatment of the patients were shown when a multidisciplinary approach was used with obligatory participation of stomatologists. Special stomatologic prophylactic and therapeutic procedures with using reamberin orally and intravenously in the chemo- and radiotherapy and adequate antibiotic therapy during the surgical operation resulted in less frequent infectious complications, that was in favour of the patients life quality. Intraosteal administration of antibiotics was shown preferable.

  3. Oral MSG administration alters hepatic expression of genes for lipid and nitrogen metabolism in suckling piglets.

    PubMed

    Chen, Gang; Zhang, Jun; Zhang, Yuzhe; Liao, Peng; Li, Tiejun; Chen, Lixiang; Yin, Yulong; Wang, Jinquan; Wu, Guoyao

    2014-01-01

    This experiment was conducted to investigate the effects of oral administration of monosodium glutamate (MSG) on expression of genes for hepatic lipid and nitrogen metabolism in piglets. A total of 24 newborn pigs were assigned randomly into one of four treatments (n = 6/group). The doses of oral MSG administration, given at 8:00 and 18:00 to sow-reared piglets between 0 and 21 days of age, were 0 (control), 0.06 (low dose), 0.5 (intermediate dose), and 1 (high dose) g/kg body weight/day. At the end of the 3-week treatment, serum concentrations of total protein and high-density lipoprotein cholesterol in the intermediate dose group were elevated than those in the control group (P < 0.05). Hepatic mRNA levels for fatty acid synthase, acetyl-coA carboxylase, insulin-like growth factor-1, glutamate-oxaloacetate transaminase, and glutamate-pyruvate transaminase were higher in the middle-dose group (P < 0.05), compared with the control group. MSG administration did not affect hepatic mRNA levels for hormone-sensitive lipase or carnitine palmitoyl transferase-1. We conclude that oral MSG administration alters hepatic expression of certain genes for lipid and nitrogen metabolism in suckling piglets.

  4. The efficacy and safety of oral pharmacokinetically enhanced amoxycillin-clavulanate 2000/125 mg, twice daily, versus oral amoxycillin-clavulanate 1000/125 mg, three times daily, for the treatment of bacterial community-acquired pneumonia in adults.

    PubMed

    Petitpretz, Patrick; Chidiac, Christian; Soriano, Francisco; Garau, Javier; Stevenson, Katharine; Rouffiac, Elisabeth

    2002-08-01

    This double-blind, double-dummy, parallel-group study was designed to show that a pharmacokinetically enhanced formulation of oral amoxycillin-clavulanate (16:1, 2000/125 mg), twice daily, is at least as effective clinically and microbiologically as oral amoxycillin-clavulanate 1000/125 mg, three times daily, in the 10 day treatment of community-acquired pneumonia (CAP) in adults. The pharmacokinetically enhanced formulation is designed to provide higher serum concentrations of amoxycillin for a longer period than standard dosing to achieve coverage of Streptococcus pneumoniae isolates with amoxycillin-clavulanic acid minimum inhibitory concentrations (MICs) up to and including 4 mg/l. A total of 344 patients with CAP from 77 centres received amoxycillin-clavulanate 2000/125 mg twice daily for 10 days (169 patients) or amoxycillin-clavulanate 1000/125 mg three times daily for 10 days (175 patients). The most common pathogen isolated was S. pneumoniae (52.3% of patients, amoxycillin-clavulanate 2000/125 mg group; 46.8% of patients, amoxycillin-clavulanate 1000/125 mg group). In the clinical per-protocol (PP) population at test of cure (days 18-39), the clinical success rate in the amoxycillin-clavulanate 2000/125 mg group was at least as good as in the amoxycillin-clavulanate 1000/125 mg group (91.5 and 93.0%, respectively; 95% CI, -8.3, 5.4). The radiological and bacteriological success rates at test of cure for the PP populations were 92.4 and 90.6% in the amoxycillin-clavulanate 2000/125 mg group and 93.9 and 84.4% in the amoxycillin-clavulanate 1000/125 mg group, respectively. The clinical, bacteriological and radiological success rates at the end of therapy (days 11-17) for the PP populations were all over 85%. Both regimens were well tolerated, with no differences in adverse events between the groups. Amoxycillin-clavulanate 2000/125 mg, twice daily, is well tolerated and at least as effective clinically as amoxycillin-clavulanate 1000/125 mg, three times

  5. Pharmacokinetics of oral neratinib during co-administration of ketoconazole in healthy subjects

    PubMed Central

    Abbas, Richat; Hug, Bruce A; Leister, Cathie; Burns, Jaime; Sonnichsen, Daryl

    2011-01-01

    AIM The primary objective was to evaluate the pharmacokinetics of a single dose of neratinib, a potent, low-molecular-weight, orally administered, irreversible pan-ErbB (ErbB-1, -2, -4) receptor tyrosine kinase inhibitor, during co-administration with ketoconazole, a potent CYP3A4 inhibitor. METHODS This was an open-label, randomized, two-period, crossover study. Fasting healthy adults received a single oral dose of neratinib 240 mg alone and with multiple oral doses of ketoconazole 400 mg. Blood samples were collected up to 72 h after each neratinib dose. Plasma concentration data were analyzed using a noncompartmental method. The least square geometric mean ratios [90% confidence interval (CI)] of Cmax(neratinib+ketoconazole) : Cmax(neratinib alone), and AUC(neratinib+ketoconazole) : AUC(neratinib alone) were assessed. RESULTS Twenty-four subjects were enrolled. Compared with neratinib administered alone, co-administration of ketoconazole increased neratinib Cmax by 3.2-fold (90% CI: 2.4, 4.3) and AUC by 4.8-fold (3.6, 6.5). Median tmax was 6.0 h with both regimens. Ketoconazole decreased mean apparent oral clearance of neratinib from 346 l h−1 to 87.1 l h−1 and increased mean elimination half-life from 11.7 h to 18.0 h. The incidence of adverse events was comparable between the two regimens (50% neratinib alone, 65% co-administration with ketoconazole). CONCLUSION Co-administration of neratinib with ketoconazole, a potent CYP3A inhibitor, increased neratinib Cmax by 3.2-fold and AUC by 4.8-fold compared with administration of neratinib alone. These results indicate that neratinib is a substrate of CYP3A and is susceptible to interaction with potent CYP3A inhibitors and, thus, dose adjustments may be needed if neratinib is administered with such compounds. PMID:21395644

  6. Daily morphine administration increases impulsivity in rats responding under a 5‐choice serial reaction time task

    PubMed Central

    Maguire, DR; Henson, C

    2016-01-01

    Background and Purpose Repeated administration of a μ opioid receptor agonist can enhance some forms of impulsivity, such as delay discounting. However, it is unclear whether repeated administration alters motor impulsivity. Experimental Approach We examined the effects of acute administration of morphine and amphetamine prior to and during daily morphine administration in rats responding under a five‐choice serial reaction time task. Rats (n = 5) were trained to detect a brief flash of light presented randomly in one of five response holes; responding in the target hole delivered food, whereas responding in the wrong hole or responding prior to illumination of the target stimulus (premature response) initiated a timeout. Premature responding served as an index of motor impulsivity. Key Results Administered acutely, morphine (0.1–10 mg·kg−1, i.p.) increased omissions and modestly, although not significantly, premature responding without affecting response accuracy; amphetamine (0.1–1.78 mg·kg−1, i.p.) increased premature responding without changing omissions or response accuracy. After 3 weeks of 10 mg·kg−1·day−1 morphine, tolerance developed to its effects on omissions whereas premature responding increased approximately fourfold, compared with baseline. Effects of amphetamine were not significantly affected by daily morphine administration. Conclusions and Implications These data suggest that repeated administration of morphine increased effects of morphine on motor impulsivity, although tolerance developed to other effects, such as omissions. To the extent that impulsivity is a risk factor for drug abuse, repeated administration of μ opioid receptor agonists, for recreational or therapeutic purposes, might increase impulsivity and thus the risk for drug abuse. PMID:26776751

  7. Comparative Proteomic Analysis of Liver Steatosis and Fibrosis after Oral Hepatotoxicant Administration in Sprague-Dawley Rats.

    PubMed

    McDyre, B Claire; AbdulHameed, Mohamed Diwan M; Permenter, Matthew G; Dennis, William E; Baer, Christine E; Koontz, Jason M; Boyle, Molly H; Wallqvist, Anders; Lewis, John A; Ippolito, Danielle L

    2018-02-01

    The past decade has seen an increase in the development and clinical use of biomarkers associated with histological features of liver disease. Here, we conduct a comparative histological and global proteomics analysis to identify coregulated modules of proteins in the progression of hepatic steatosis or fibrosis. We orally administered the reference chemicals bromobenzene (BB) or 4,4'-methylenedianiline (4,4'-MDA) to male Sprague-Dawley rats for either 1 single administration or 5 consecutive daily doses. Livers were preserved for histopathology and global proteomics assessment. Analysis of liver sections confirmed a dose- and time-dependent increase in frequency and severity of histopathological features indicative of lipid accumulation after BB or fibrosis after 4,4'-MDA. BB administration resulted in a dose-dependent increase in the frequency and severity of inflammation and vacuolation. 4,4'-MDA administration resulted in a dose-dependent increase in the frequency and severity of periportal collagen accumulation and inflammation. Pathway analysis identified a time-dependent enrichment of biological processes associated with steatogenic or fibrogenic initiating events, cellular functions, and toxicological states. Differentially expressed protein modules were consistent with the observed histology, placing physiologically linked protein networks into context of the disease process. This study demonstrates the potential for protein modules to provide mechanistic links between initiating events and histopathological outcomes.

  8. Safety of fluralaner oral solution, a novel systemic antiparasitic treatment for chickens, in laying hens after oral administration via drinking water.

    PubMed

    Prohaczik, Angella; Menge, Monika; Huyghe, Bruno; Flochlay-Sigognault, Annie; Traon, Gaëlle Le

    2017-08-08

    Poultry mites are the most significant pest affecting production systems in the egg-laying industry. Fluralaner is a novel systemic insecticide and acaricide that is effective against poultry mites (Dermanyssus gallinae, Ornithonyssus sylviarum) in chickens after oral administration. This study investigated the safety of oral administration of a 1% solution of fluralaner in drinking water to laying hens at the recommended treatment dose and at multiples of this dose. One hundred-twenty healthy 28-week-old laying hens, weighing 1.4-2.1 kg at first administration, were included in the study, and allocated to 4 treatment groups of 30 hens each receiving daily doses of 0, 0.5, 1.5 and 2.5 mg fluralaner/kg body weight, equivalent to 0, 1, 3, and 5 times the recommended dose of fluralaner. The product was administered via drinking water on a total of six occasions, as 3-day treatment periods twice with an interval of 4 days with no treatment (treatment on days 1, 2, 3 and 8, 9, 10), representing 3 times the recommended number of administrations. Hens supplied with non-medicated drinking water served as controls. During the study, all hens were clinically observed, and their health was carefully monitored including body weight, food and water consumption, hematology, clinical chemistry, and withdrawal reflex test. Eggs laid over the study were evaluated for main characteristics (e.g. weight, shape, strength, shell thickness and soundness, albumen height, yolk color, Haugh unit and presence of blood and/or meat spots). Following euthanasia of the hens at the end of the second treatment period (day 11) or 18 days later (day 29), complete gross post-mortem examination, including organ weight determination, and histopathological examination of multiple tissues were conducted. There were no clinical findings related to fluralaner treatment. Statistically significant differences between the treated groups and the control group were observed for some clinical pathology

  9. Pharmacokinetics of butorphanol after intravenous, intramuscular, and oral administration in Hispaniolan Amazon parrots (Amazona ventralis).

    PubMed

    Guzman, David Sanchez-Migallon; Flammer, Keven; Paul-Murphy, Joanne R; Barker, Steven A; Tully, Thomas N

    2011-09-01

    Previous studies have validated the clinical use of opioids with kaap-receptor affinities for pain management in birds. Butorphanol, a kappa opioid receptor agonist and a mu opioid receptor antagonist, is currently considered by many clinicians to be the opioid of choice for this use. However, despite studies reporting the analgesic properties of butorphanol in psittacine birds, dosing intervals have not been established for any psittacine species. The goals of this study in the Hispaniolan Amazon parrot (Amazona ventralis) were to evaluate the pharmacokinetics of butorphanol tartrate after intravenous (IV), intramuscular (IM), and oral (PO) administration and to determine the bioavailability of butorphanol tartrate after oral administration. Twelve Hispaniolan Amazon parrots were used in the study, with a complete-crossover experimental design and a 3-month period separating each part of the study. The birds were randomly assigned to 3 groups (n = 4) for each stage. Butorphanol tartrate was administered once at a dose of 5 mg/kg in the basilic vein or pectoral muscles or as an oral solution delivered via feeding tube into the crop for the IV, IM, and PO studies, respectively. After butorphanol administration, blood samples were collected at 1, 5, 15, 30, 60, 90, 120, 180, and 240 minutes for the IV and IM studies and at 5, 15, 30, 60, 90, 120, 180, 240, and 300 minutes for the PO study. Because of the size limitation of the birds, naive pooling of datum points was used to generate a mean plasma butorphanol concentration at each time point. For each study, birds in each group (n = 4) were bled 3 times after dosing. Plasma butorphanol concentrations were determined by high-performance liquid chromatography/tandem mass spectrometry, and pharmacokinetic parameters were calculated. Butorphanol tartrate was found to have high bioavailability and rapid elimination following IM administration. In contrast, oral administration resulted in low bioavailability (< 10%), thus

  10. Assessing the validity and reliability of the Malagasy version of Oral Impacts on Daily Performance (OIDP): a cross-sectional study.

    PubMed

    Razanamihaja, Noeline; Ranivoharilanto, Eva

    2017-01-01

    Evaluating health needs includes measures of the impact of state of health on the quality of life. This entails evaluating the psychosocial aspects of health. To achieve this, several tools for measuring the quality of life related to oral health have been developed. However, it is vital to evaluate the psychometric properties of these tools so they can be used in a new context and on a new population. The purpose of this study was to evaluate the reliability and validity of the Malagasy version of a questionnaire for studying the impacts of oral-dental health on daily activities (Oral Impacts on Daily Performance), and analyse the interrelations between the scores obtained and the oral health indicators. A cross-sectional study was performed for the transcultural adaptation of the Oral Impacts on Daily Performance questionnaire forward translated and back-translated from English to Malagasy and from Malagasy to English, respectively. The psychometric characteristics of the Malagasy version of the Oral Impacts on Daily Performance were then evaluated in terms of internal reliability, test-retest, and construct, criteria and discriminant validity. Four hundred and six adults responded in face-to-face interviews to the Malagasy version of the Oral Impacts on Daily Performance questionnaire. Nearly 74% of the participants indicated impacts of their oral health on their performance in their daily lives during the 6 months prior to the survey. The activities most affected were: "smiling", "eating" and "sleeping and relaxing". Cronbach's alpha was 0.87. The construct validity was demonstrated by a significant association between the Oral Impacts on Daily Performance scores and the subjective evaluation of oral health ( p <0.001). Discriminant validity was demonstrated by the fact that the Oral Impacts on Daily Performance scores were significantly higher in subjects with more than ten missing teeth, compared to those with fewer than ten missing teeth ( p  < 0

  11. Pharmacokinetics of penciclovir after oral administration of its prodrug famciclovir to horses.

    PubMed

    Tsujimura, Koji; Yamada, Masayuki; Nagata, Shun-ichi; Yamanaka, Takashi; Nemoto, Manabu; Kondo, Takashi; Kurosawa, Masahiko; Matsumura, Tomio

    2010-03-01

    We investigated the pharmacokinetics of penciclovir after oral administration of its prodrug famciclovir to horses. Following an oral dose of famciclovir at 20 mg/kg, maximum plasma concentrations of penciclovir occurred between 0.75 and 1.5 hr (mean 0.94 + or - 0.38 hr) after dosing and were in the range 2.22 to 3.56 microg/ml (mean 2.87 + or - 0.61 microg/ml). The concentrations of penciclovir declined in a biphasic manner after the peak concentration was attained. The mean half-life of the rapid elimination phase was 1.73 + or - 0.34 hr whereas that of the slow elimination phase was 34.34 + or - 13.93 hr. These pharmacokinetic profiles observed were similar to those of another antiherpesvirus drug, acyclovir, previously reported in horses following oral dosing of its prodrug valacyclovir.

  12. Daily vs every other day administration of G-CSF following autologous peripheral stem cell transplantation: a prospective randomized study.

    PubMed

    Ozkan, Hasan Atilla; Ozer, Ufuk Guney; Bal, Cengiz; Gulbas, Zafer

    2013-10-01

    The purpose of the study was to evaluate whether every other day administration of G-CSF was as safe and efficient as daily administration of G-CSF on neutrophil engraftment following autologous peripheral stem cell transplantation (APSCT). Duration of G-CSF administration, incidence of blood stream infections, duration of febrile neutropenia, duration of non-prophylactic antibiotic therapy, transfusion requirements, duration of hospitalization and G-CSF costs were also studied. Forty-seven patients with diagnosis of lymphoma and multiple myeloma undergoing APSCT were randomized to receive post-transplant daily or every other day G-CSF therapy both beginning on day +1. Both groups were comparable with regard to patient characteristics. There was no significant difference in time to neutrophil engraftment (p=0.31). The duration of G-CSF administration was significantly less in the every other day group (p<0.001). There were no detectable differences seen in the number of febrile days, duration of non-prophylactic antibiotics, the incidence of blood stream infections, transfusion requirements and the duration of hospitalization. There was a trend towards a faster platelet recovery in the every other day group, although the difference was not statistically significant (p=0.059). The number of doses of G-CSF used per transplant is significantly reduced, resulting in a significant reduction in drug costs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Once-daily, oral levofloxacin monotherapy for low-risk neutropenic fever in cancer patients: a pilot study in China

    PubMed Central

    He, Lixian; Zhao, Su; Weng, Heng; Yang, Guowang

    2015-01-01

    This pilot study assesses the safety and efficacy of once-daily, oral levofloxacin monotherapy in Chinese patients with low-risk febrile neutropenia. In this prospective, single-arm, open-label, multicenter clinical trial, 46 adult Chinese patients with solid tumors and low-risk febrile neutropenia were included. Patients received oral levofloxacin monotherapy (500 mg orally/day) until day 12, followed by 7 days of follow-up (day 19). Body temperature was measured three times per day. On days 2, 3, 5–7, 9, 12, and 19, disease symptoms and vital signs were recorded, adverse drug reactions were assessed, and blood samples were collected to determine the whole-blood cell count and the absolute neutrophil count. Blood cultures and chest radiographs were performed simultaneously until negative results were found. Oral levofloxacin was effective and well tolerated in 97.6% of patients irrespective of the cancer type and cause of fever. Body temperature began to decline in 24.4, 68.3, and 90.2% of patients, respectively, at 12, 24, and 48 h after initiating levofloxacin therapy. On days 5 and 7, 95.1 and 97.6% of the patients had complete defervescence, respectively. The median time for absolute neutrophil count recovery to at least 1500/mm3 after initiation of treatment was 3 days. Only one patient reported mild diarrhea. This pilot study showed that oral levofloxacin quickly and effectively reduced fever, initiated neutrophil recovery, and was well tolerated in Chinese low-risk febrile neutropenic patients with solid tumors. Further study is needed to compare patient data of levofloxacin with the standard amoxicillin/ciprofloxacin protocol in this population for both safety and efficacy. PMID:25486597

  14. Effects of Oral Glucosamine Hydrochloride Administration on Plasma Free Amino Acid Concentrations in Dogs

    PubMed Central

    Azuma, Kazuo; Osaki, Tomohiro; Tsuka, Takeshi; Imagawa, Tomohiro; Okamoto, Yoshiharu; Takamori, Yoshimori; Minami, Saburo

    2011-01-01

    We examined the effects of oral glucosamine hydrochloride (GlcN), N-acetyl-d-glucosamine (GlcNAc) and d-glucose (Glc) administration on plasma total free amino acid (PFAA) concentrations in dogs. The PFAA concentrations increased in the control group and the GlcNAc group at one hour after feeding, and each amino acid concentration increased. On the other hand, in the GlcN group and the Glc group PFAA concentrations decreased at one hour after feeding. A significant decrease in amino acid concentration was observed for glutamate, glycine and alanine. Our results suggest the existence of differences in PFAA dynamics after oral administration of GlcN and GlcNAc in dogs. PMID:21673884

  15. Pharmacokinetics of tramadol and its major metabolites in alpacas following intravenous and oral administration.

    PubMed

    Edmondson, M A; Duran, S H; Boothe, D M; Stewart, A J; Ravis, W R

    2012-08-01

    Tramadol, a centrally acting opioid analgesic with monamine reuptake inhibition, was administered to six alpacas (43-71 kg) randomly assigned to two treatment groups, using an open, single-dose, two-period, randomized cross-over design at a dose of 3.4-4.4 mg/kg intravenously (i.v.) and, after a washout period, 11 mg/kg orally. Serum samples were collected and stored at -80°C until assayed by HPLC. Pharmacokinetic parameters were calculated. The mean half-lives (t(1/2)) i.v. were 0.85±0.463 and 0.520±0.256 h orally. The Cp(0) i.v. was 2467±540 ng/mL, and the C(max) was 1202±1319 ng/mL orally. T(max) occurred at 0.111±0.068 h orally. The area under the curve (AUC(0-∞)) i.v. was 895±189 and 373±217 ng*h/mL orally. The volume of distribution (V(d[area])) i.v. was 5.50±2.66 L/kg. Total body clearance (Cl) i.v. was 4.62±1.09 h; Cl/F for oral administration was 39.5±23 L/h/kg. The i.v. mean residence time (MRT) was 0.720±0.264. Oral adsorption (F) was low (5.9-19.1%) at almost three times the i.v. dosage with a large inter-subject variation. This may be due to binding with the rumen contents or enzymatic destruction. Assuming linear nonsaturable pharmacokinetics and absorption processes, a dosage of 6.7 times orally would be needed to achieve the same i.v. serum concentration of tramadol. The t(1/2) of all three metabolites was longer than the parent drug; however, O-DMT, N-DMT, and Di-DMT metabolites were not detectable in all of the alpacas. Because of the poor bioavailability and adverse effects noted in this study, the oral administration of tramadol in alpacas cannot be recommended without further research. © 2011 Blackwell Publishing Ltd.

  16. Minor oral surgery without stopping daily low-dose aspirin therapy: a study of 51 patients.

    PubMed

    Madan, Gautam A; Madan, Sonal G; Madan, Gauri; Madan, A D

    2005-09-01

    The risk of excessive bleeding prompts physicians to stop low-dose long-term aspirin regimens before surgery, which puts the patient at risk from adverse thrombotic events. We hypothesize that most minor oral surgical procedures can be carried out safely without stopping low-dose aspirin. All minor oral surgery patients at our hospital (Madan Dental Hospital, Ahmedabad, India) from May 2002 to May 2003, who were also on long-term low-dose aspirin therapy regimens (acetylsalicylic acid 75 mg to 100 mg/day), were included. Investigation of bleeding time and platelet count was performed. If within normal limits, aspirin was not stopped before surgery. Patients were operated under local anesthesia on an outpatient basis. All wounds were sutured and followed up at 24, 48, and 72 hours, 1 week, and 2 weeks after the procedure. The study included 51 patients (32 males, 19 females), ranging in age from 45 to 70 years. Preoperative values were within normal limits for all patients. Aspirin was not stopped for a single patient. There was no excessive intraoperative bleeding in all cases except 1; there was no postoperative bleeding in all cases. We conclude that most minor oral surgery procedures can be carried out safely without stopping long-term low-dose aspirin regimen.

  17. Promotion or suppression of experimental metastasis of B16 melanoma cells after oral administration of lapachol

    SciTech Connect

    Maeda, Masayo; Murakami, Manabu; Takegami, Tsutomu

    Lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone] is a vitamin K antagonist with antitumor activity. The effect of lapachol on the experimental metastasis of murine B16BL6 melanoma cells was examined. A single oral administration of a high toxic dose of lapachol (80-100 mg/kg) 6 h before iv injection of tumor cells drastically promoted metastasis. This promotion of metastasis was also observed in T-cell-deficient mice and NK-suppressed mice. In vitro treatment of B16BL6 cells with lapachol promoted metastasis only slightly, indicating that lapachol promotes metastasis primarily by affecting host factors other than T cells and NK cells. A single oral administration of warfarin, the most commonlymore » used vitamin K antagonist, 6 h before iv injection of tumor cells also drastically promoted the metastasis of B16BL6 cells. The promotion of metastasis by lapachol and warfarin was almost completely suppressed by preadministration of vitamin K3, indicating that the promotion of metastasis by lapachol was derived from vitamin K antagonism. Six hours after oral administration of lapachol or warfarin, the protein C level was reduced maximally, without elongation of prothrombin time. These observations suggest that a high toxic dose of lapachol promotes metastasis by inducing a hypercoagulable state as a result of vitamin K-dependent pathway inhibition. On the other hand, serial oral administration of low non-toxic doses of lapachol (5-20 mg/kg) weakly but significantly suppressed metastasis by an unknown mechanism, suggesting the possible use of lapachol as an anti-metastatic agent.« less

  18. Supraspinally-administered agmatine attenuates the development of oral fentanyl self-administration

    PubMed Central

    Wade, Carrie L.; Schuster, Daniel J.; Domingo, Kristine M.; Kitto, Kelley F.; Fairbanks, Carolyn A.

    2009-01-01

    The decarboxylation product of arginine, agmatine, has effectively reduced or prevented opioid-induced tolerance and dependence when given either systemically (intraperitoneally or subcutaneously) or centrally (intrathecally or intracerebroventricularly). Systemically administered agmatine also reduces the escalation phase of intravenous fentanyl self-administration in rats. The present study assessed whether centrally (intracerebroventricular, i.c.v.) delivered agmatine could prevent the development of fentanyl self-administration in mice. Mice were trained to respond under a fixed-ratio 1 (FR1) schedule for either fentanyl (0.7 μg/70 μl, p.o.) or food reinforcement. Agmatine (10 nmol/5 μl), injected i.c.v. 12-14h before the first session and every other evening (12-14h before session) for 2 weeks, completely attenuated oral fentanyl self-administration (but not food-maintained responding) compared to saline-injected controls. When agmatine was administered after fentanyl self-administration had been established (day 8) it had no attenuating effects on bar pressing. This dose of agmatine does not decrease locomotor activity as assessed by rotarod. The present findings significantly extend the previous observation that agmatine prevents opioid-maintained behavior to a chronic model of oral fentanyl self-administration as well as identifying a supraspinal site of action for agmatine inhibition of drug addiction. PMID:18495108

  19. Field trial of GABA-fortified rice plants and oral administration of milled rice in spontaneously hypertensive rats.

    PubMed

    Kowaka, Emi; Shimajiri, Yasuka; Kawakami, Kouhei; Tongu, Miki; Akama, Kazuhito

    2015-06-01

    Hypertension is one of the most critical risk factors accompanying cardiovascular diseases. γ-Aminobutyric acid (GABA) is a non-protein amino acid that functions as a major neurotransmitter in mammals and also as a blood-pressure lowering agent. We previously produced GABA-fortified rice lines of a popular Japonica rice cultivar 'Koshihikari' by genetic manipulation of GABA shunt-related genes. In the study reported here, we grew these same novel rice lines in a field trial and administered the milled rice orally to rats. The yield parameters of the transgenic rice plants were almost unchanged compared to those of untransformed cv. 'Koshihikari' plants, while the rice grains of the transgenic plants contained a high GABA content (3.5 g GABA/kg brown rice; 0.75-0.85 GABA g/kg milled rice) in a greenhouse trial. Oral administration of a diet containing 2.5% GABA-fortified rice, with a daily intake for 8 weeks, had an approximately 20 mmHg anti-hypertensive effect in spontaneous hypertensive rats but not in normotensive Wistar-Kyoto rats. These results suggest that GABA-fortified rice may be applicable as a staple food to control or prevent hypertension.

  20. Pharmacokinetics of brotizolam in healthy subjects following intravenous and oral administration

    PubMed Central

    Jochemsen, Roeline; Wesselman, J. G. J.; Hermans, J.; van Boxtel, C. J.; Breimer, D. D.

    1983-01-01

    1 Pharmacokinetics and bioavailability of brotizolam after i.v. and oral administration were studied in healthy young volunteers. 2 Kinetic parameters after i.v. administration were: volume of distribution 0.66 ± 0.19 1/kg, total plasma clearance 113 ± 28 ml/min, distribution half-life 11 ± 6 min, and elimination half-life 4.8 ± 1.4 h (mean values ± s.d.). 3 Kinetic parameters after oral administration were: absorption lag-time 8 ± 12 min, absorption half-life 10 ± 11 min, and elimination half-life 5.1 ± 1.2 h (mean values ± s.d.). 4 Bioavailability of brotizolam was 70 ± 22% when calculated by comparing oral and intravenous area-under-curve values, corrected for intra-individual half-life differences. An alternative calculation method, which is relatively independent of large clearance variations, provided a bioavailability of 70 ± 24% (range: 47-117%). PMID:6661374

  1. Oral Administration of Recombinant Lactococcus lactis Expressing the Cellulase Gene Increases Digestibility of Fiber in Geese.

    PubMed

    Zhou, Haizhu; Gao, Yunhang; Gao, Guang; Lou, Yujie

    2015-12-01

    Enhancing cellulose digestibility in animals is important for improving the utilization of forage, which can decrease the amount of food used in animal production. The aim of the present study was to achieve recombinant expression of the cellulase gene in Lactococcus lactis and evaluate the effects of oral administration of the recombinant L. lactis on fiber digestibility in geese. Cellulase (Cell) and green fluorescent protein (GFP) genes were cloned into a L. lactis expression vector (pNZ8149) to construct the recombinant expression plasmid (pNZ8149-GFP-Cell). Then, the recombinant expression plasmid was transformed into L. lactis (NZ3900) competent cells by electroporation to obtain recombinant L. lactis (pNZ8149-GFP-Cell/NZ3900) in which protein expression was induced by Nisin. Expression of GFP and Cell by the recombinant L. lactis was confirmed using SDS-PAGE, fluorescence detection, and Congo red assays. A feeding experiment showed that oral administration of pNZ8149-GFP-Cell/NZ3900 significantly increased the digestibility of dietary fiber in geese fed either a maize stalk diet or a rice chaff diet. Therefore, oral administration of recombinant L. lactis cells expressing the cellulase gene increases fiber digestibility in geese, offering a way to increase the utilization of dietary fiber in geese.

  2. Detection of capecitabine (Xeloda®) on the skin surface after oral administration

    NASA Astrophysics Data System (ADS)

    Huang, Mao-Dong; Fuss, Harald; Lademann, Jürgen; Florek, Stefan; Patzelt, Alexa; Meinke, Martina C.; Jung, Sora

    2016-04-01

    Palmoplantar erythrodysesthesia (PPE), or hand-foot syndrome, is a cutaneous toxicity under various chemotherapeutics contributing to the most frequent side effects in patients treated with capecitabine (Xeloda®). The pathomechanism of PPE has been unclear. Here, the topical detection of capecitabine in the skin after oral application was shown in 10 patients receiving 2500 mg/m2/day capecitabine. Sweat samples were taken prior to and one week after oral administration of capecitabine. Using high-resolution continuum source absorption spectrometry, the changes in concentrations of fluorine, which is an ingredient of capecitabine, were quantified and statistically analyzed. Here, we show an increase in fluorine concentrations from 40±10 ppb (2±0.5 pM) before capecitabine administration to 27.7±11.8 ppm (14.6±6.5 nM) after application, p<0.001. The results show the secretion of capecitabine on the skin surface after oral administration, indicating a local toxic effect as a possible pathomechanism of PPE.

  3. Flurbiprofen concentration in soft tissues is higher after topical application than after oral administration

    PubMed Central

    Kai, Shuken; Kondo, Eiji; Kawaguchi, Yasuyuki; Kitamura, Nobuto; Yasuda, Kazunori

    2013-01-01

    Aim To compare tissue concentrations of flurbiprofen resulting from topical application and oral administration according to the regulatory approved dosing guidelines. Method Sixteen patients were included in this study. Each patient was randomly assigned to the topical application or oral administration group. In each group, a pair of tapes or a tablet, containing a total of 40 mg flurbiprofen, was administered twice at 16 and 2 h before the surgery. Results The flurbiprofen concentration in the fat, tendon, muscle and periosteum tissues was significantly higher (P < 0.0330) after topical application (992 ng g−1 [95% CI 482, 1503], 944 [95% CI 481, 1407], 492 [95% CI 248, 735], and 455 [95% CI 153, 756], respectively) than after oral administration (150 ng g−1 [95% CI 84, 217], 186 [95% CI 118, 254], 82 [95% CI 49, 116],and 221 [95% CI, 135, 307], respectively). Conclusion Topical application is an effective method to deliver flurbiprofen to the human body, particularly to soft tissues near the body surface. PMID:22822928

  4. Improved stability and immunological potential of tetanus toxoid containing surface engineered bilosomes following oral administration.

    PubMed

    Jain, Sanyog; Harde, Harshad; Indulkar, Anura; Agrawal, Ashish Kumar

    2014-02-01

    The present study was designed with the objective to investigate the stability and potential of glucomannan-modified bilosomes (GM-bilosomes) in eliciting immune response following oral administration. GM-bilosomes exhibited desired quality attributes simultaneously maintaining the chemical and conformation stability of the tetanus toxoid (TT) entrapped in to freeze dried formulations. The GM-bilosomes exhibited excellent stability in different simulated biological fluids and sustained release profile up to 24 h. GM-bilosomes elicited significantly higher (P<0.05) systemic immune response (serum IgG level) as compared to bilosomes, niosomes and alum adsorbed TT administered through oral route. More importantly, GM-bilosomes were found capable of inducing mucosal immune response, i.e. sIgA titre in salivary and intestinal secretions as well as cell mediated immune response (IL-2 and IFN-γ levels in spleen homogenate) which was not induced by i.m. TT, the conventional route of immunization. Conclusively, GM-bilosomes could be considered as a promising carrier and adjuvant system for oral mucosal immunization. This team reports on the development and effects of a glucomannan-modified bilosome as an oral vaccine vector, using tetanus toxoid in the experiments. These GM-bilosomes not only elicited significantly higher systemic immune response as compared to bilosomes, niosomes and alum adsorbed orally administered TT, but also demonstrated mucosal immune response induction as well as cell mediated immune responses, which were not induced by the conventional route of immunization. © 2014.

  5. Oral drug self-administration: an overview of laboratory animal studies.

    PubMed

    Meisch, R A

    2001-06-01

    Many abused drugs can be established as orally delivered reinforcers for rhesus monkeys and other animals. Benzodiazepines, barbiturates, opioids, psychomotor stimulants, dissociative anesthetics, and ethanol can come to serve as reinforcers when taken by mouth. The principal problems in establishing drugs as reinforcers by the oral route of administration are (1) aversive taste, (2) delay in onset of central nervous system effects, and (3) consumption of low volumes of drug solution. Strategies have been devised to successfully overcome these problems, and orally delivered drugs can be established as effective reinforcers. Reinforcing actions are demonstrated by consumption of greater volumes of drug solution than volumes of the water vehicle, and supporting evidence for reinforcing effects consists of the maintenance of behavior under intermittent schedules of reinforcement and the generation of orderly dose-response functions. This article presents an overview of studies of behavior reinforced by oral drug reinforcement. Factors that control oral drug intake include dose, schedule of reinforcement, food restriction, and alternative reinforcers. Many drugs, administered by the experimenter, can alter oral drug reinforcement. Relative reinforcing effects can be assessed by choice procedures and by persistence of behavior across increases in schedule size. In general, reinforcing effects increase directly with dose. Rhesus monkeys prefer combinations of reinforcing drugs to the component drugs. The taste of drug solutions may act as a conditioned reinforcer and a discriminative stimulus. Consequences of drug intake include tolerance and physiological dependence. Findings with orally self-administered drugs are similar to many findings with other positive reinforcers, including intravenously self-administered drugs.

  6. Therapeutic efficacy induced by the oral administration of Agaricus blazei Murill against Leishmania amazonensis.

    PubMed

    Valadares, Diogo G; Duarte, Mariana C; Ramírez, Laura; Chávez-Fumagalli, Miguel A; Lage, Paula S; Martins, Vivian T; Costa, Lourena E; Ribeiro, Tatiana G; Régis, Wiliam C B; Soto, Manuel; Fernandes, Ana Paula; Tavares, Carlos A P; Coelho, Eduardo A F

    2012-10-01

    The development of therapeutic alternatives to treat leishmaniasis has received considerable attention. The present study aimed to investigate the efficacy of the Agaricus blazei Murill water extract (AbM) to treat BALB/c mice infected with Leishmania amazonensis. First, a dose-titration curve was performed. The most well-defined concentration able to induce the most effective results in the infected animals, considering a daily administration of the product, was that of 100 mg kg(-1) day(-1). In this context, the AbM was administered orally, beginning on day 0 up to 20 days postinfection. Additional animals were treated with amphotericin B (AmpB, 5 mg kg(-1) day(-1)) by peritoneal route for the same period of time, while the control group received distilled water. The animals were evaluated at 14 weeks post-infection, at which time the parasitological and immunological parameters were analyzed. Mice treated with the AbM presented a 60% reduction in the inflammation of infected footpads as compared to untreated control-infected mice. Moreover, in the treated mice, as compared to the untreated controls, approximately 60 and 66% reductions could be observed in the parasite burdens of the footpad and draining lymph nodes, respectively. In addition, no parasites could be detected in the spleen of treated mice at week 14 postinfection. These treated animals produced significantly higher levels of interferon gamma (IFN-γ) and nitric oxide (NO), higher levels of parasite-specific IgG2a isotype antibodies, and lower levels of interleukin (IL)-4, and IL-10 in the spleen and lymph node cell cultures than did the controls. Differences could be observed by comparing animals treated with AbM to those treated with AmpB, as indicated by a significant reduction in tissue parasitism, higher levels of IFN-γ and NO, and lower levels of IL-4 and IL-10, as well as by a decreased hepatic toxicity. In conclusion, the present study's data show that the A. blazei Murill water extract

  7. Implications of chronic daily anti-oxidant administration on the inflammatory response to intracortical microelectrodes

    NASA Astrophysics Data System (ADS)

    Potter-Baker, Kelsey A.; Stewart, Wade G.; Tomaszewski, William H.; Wong, Chun T.; Meador, William D.; Ziats, Nicholas P.; Capadona, Jeffrey R.

    2015-08-01

    Objective. Oxidative stress events have been implicated to occur and facilitate multiple failure modes of intracortical microelectrodes. The goal of the present study was to evaluate the ability of a sustained concentration of an anti-oxidant and to reduce oxidative stress-mediated neurodegeneration for the application of intracortical microelectrodes. Approach. Non-functional microelectrodes were implanted into the cortex of male Sprague Dawley rats for up to sixteen weeks. Half of the animals received a daily intraperitoneal injection of the natural anti-oxidant resveratrol, at 30 mg kg-1. The study was designed to investigate the biodistribution of the resveratrol, and the effects on neuroinflammation/neuroprotection following device implantation. Main results. Daily maintenance of a sustained range of resveratrol throughout the implantation period resulted in fewer degenerating neurons in comparison to control animals at both two and sixteen weeks post implantation. Initial and chronic improvements in neuronal viability in resveratrol-dosed animals were correlated with significant reductions in local superoxide anion accumulation around the implanted device at two weeks after implantation. Controls, receiving only saline injections, were also found to have reduced amounts of accumulated superoxide anion locally and less neurodegeneration than controls at sixteen weeks post-implantation. Despite observed benefits, thread-like adhesions were found between the liver and diaphragm in resveratrol-dosed animals. Significance. Overall, our chronic daily anti-oxidant dosing scheme resulted in improvements in neuronal viability surrounding implanted microelectrodes, which could result in improved device performance. However, due to the discovery of thread-like adhesions, further work is still required to optimize a chronic anti-oxidant dosing regime for the application of intracortical microelectrodes.

  8. Pharmacokinetics after oral and intravenous administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis).

    PubMed

    Souza, Marcy J; Sanchez-Migallon Guzman, David; Paul-Murphy, Joanne R; Cox, Sherry K

    2012-08-01

    To determine pharmacokinetics after IV and oral administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 9 healthy adult Hispaniolan Amazon parrots (3 males, 5 females, and 1 of unknown sex). Tramadol (5 mg/kg, IV) was administered to the parrots. Blood samples were collected from -5 to 720 minutes after administration. After a 3-week washout period, tramadol (10 and 30 mg/kg) was orally administered to parrots. Blood samples were collected from -5 to 1,440 minutes after administration. Three formulations of oral suspension (crushed tablets in a commercially available suspension agent, crushed tablets in sterile water, and chemical-grade powder in sterile water) were evaluated. Plasma concentrations of tramadol and its major metabolites were measured via high-performance liquid chromatography. Mean plasma tramadol concentrations were > 100 ng/mL for approximately 2 to 4 hours after IV administration of tramadol. Plasma concentrations after oral administration of tramadol at a dose of 10 mg/kg were < 40 ng/mL for the entire time period, but oral administration at a dose of 30 mg/kg resulted in mean plasma concentrations > 100 ng/mL for approximately 6 hours after administration. Oral administration of the suspension consisting of the chemical-grade powder resulted in higher plasma tramadol concentrations than concentrations obtained after oral administration of the other 2 formulations; however, concentrations differed significantly only at 120 and 240 minutes after administration. Oral administration of tramadol at a dose of 30 mg/kg resulted in plasma concentrations (> 100 ng/mL) that have been associated with analgesia in Hispaniolan Amazon parrots.

  9. Reduction in labile plasma iron during treatment with deferasirox, a once-daily oral iron chelator, in heavily iron-overloaded patients with β-thalassaemia

    PubMed Central

    Daar, Shahina; Pathare, Anil; Nick, Hanspeter; Kriemler-Krahn, Ulrike; Hmissi, Abdel; Habr, Dany; Taher, Ali

    2009-01-01

    This subgroup analysis evaluated the effect of once-daily oral deferasirox on labile plasma iron (LPI) levels in patients from the prospective, 1-yr, multicentre ESCALATOR study. Mean baseline liver iron concentration and median serum ferritin levels were 28.6 ± 10.3 mg Fe/g dry weight and 6334 ng/mL respectively, indicating high iron burden despite prior chelation therapy. Baseline LPI levels (0.98 ± 0.82 μmol/L) decreased significantly to 0.12 ± 0.16 μmol/L, 2 h after first deferasirox dose (P=0.0006). Reductions from pre- to post-deferasirox administration were also observed at all other time points. Compared to baseline, there was a significant reduction in preadministration LPI that reached the normal range at week 4 and throughout the remainder of the study (P≤0.02). Pharmacokinetic analysis demonstrated an inverse relationship between preadministration LPI levels and trough deferasirox plasma concentrations. Once-daily dosing with deferasirox ≥20 mg/kg/d provided sustained reduction in LPI levels in these heavily iron-overloaded patients, suggesting 24-h protection from LPI. Deferasirox may therefore reduce unregulated tissue iron loading and prevent further end-organ damage. PMID:19191863

  10. Antinociceptive effects after oral administration of tramadol hydrochloride in Hispaniolan Amazon parrots (Amazona ventralis).

    PubMed

    Sanchez-Migallon Guzman, David; Souza, Marcy J; Braun, Jana M; Cox, Sherry K; Keuler, Nicholas S; Paul-Murphy, Joanne R

    2012-08-01

    To evaluate antinociceptive effects on thermal thresholds after oral administration of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). Animals-15 healthy adult Hispaniolan Amazon parrots. 2 crossover experiments were conducted. In the first experiment, 15 parrots received 3 treatments (tramadol at 2 doses [10 and 20 mg/kg] and a control suspension) administered orally. In the second experiment, 11 parrots received 2 treatments (tramadol hydrochloride [30 mg/kg] and a control suspension) administered orally. Baseline thermal foot withdrawal threshold was measured 1 hour before drug or control suspension administration; thermal foot withdrawal threshold was measured after administration at 0.5, 1.5, 3, and 6 hours (both experiments) and also at 9 hours (second experiment only). For the first experiment, there were no overall effects of treatment, hour, period, or any interactions. For the second experiment, there was an overall effect of treatment, with a significant difference between tramadol hydrochloride and control suspension (mean change from baseline, 2.00° and -0.09°C, respectively). There also was a significant change from baseline for tramadol hydrochloride at 0.5, 1.5, and 6 hours after administration but not at 3 or 9 hours after administration. Tramadol at a dose of 30 mg/kg, PO, induced thermal antinociception in Hispaniolan Amazon parrots. This dose was necessary for induction of significant and sustained analgesic effects, with duration of action up to 6 hours. Further studies with other types of noxious stimulation, dosages, and intervals are needed to fully evaluate the analgesic effects of tramadol hydrochloride in psittacines.

  11. Efficacy of orally administered maropitant citrate in preventing vomiting associated with hydromorphone administration in dogs.

    PubMed

    Hay Kraus, Bonnie L

    2014-05-15

    To evaluate the effectiveness of orally administered maropitant citrate in preventing vomiting after hydromorphone hydrochloride administration in dogs. Randomized, blinded, prospective clinical study. 40 dogs with American Society of Anesthesiologists status of I or II, > 6 months of age, and weighing between 24 and 58.2 kg (52.8 and 128.04 lb). Dogs were randomly selected to receive maropitant (2.0 to 4.0 mg/kg [0.9 to 1.8 mg/lb]) or placebo (lactose monohydrate) orally 2 hours prior to receiving hydromorphone (0.1 mg/kg [0.045 mg/lb], IM). A blinded observer recorded the occurrence of vomiting or signs of nausea (eg, salivation or lip-licking) during a 30-minute period after hydromorphone administration. Two-tailed Fisher exact tests were used to compare the incidences of vomiting and signs of nausea with or without vomiting between treatment groups. Results-Of the 20 dogs receiving maropitant, none vomited but 12 (60%) developed signs of nausea. Of the 20 dogs receiving placebo, 5 (25%) vomited and 11 (55%) developed signs of nausea; overall, 16 of 20 (80%) dogs in the placebo treatment group vomited or developed signs of nausea. Compared with the effects of placebo, maropitant significantly decreased the incidence of vomiting but not signs of nausea in dogs administered hydromorphone. Among the 40 study dogs, the incidence of vomiting associated with hydromorphone administration was 25%. Oral administration of maropitant prevented vomiting but not signs of nausea associated with hydromorphone administration in dogs.

  12. Routine use of daily oral vitamin K to treat infants with cystic fibrosis.

    PubMed

    Cottam, Sophie T; Connett, Gary J

    2015-10-01

    Vitamin K is routinely administered after birth in the UK to prevent haemorrhagic disease of the newborn. Despite this, vitamin K-deficient coagulopathy still occurs in infants with high morbidity and mortality. Up to 50% of late onset bleeding presents with intracranial haemorrhage. The risk of developing vitamin K coagulopathy is higher in infants with cystic fibrosis (CF) and those that are exclusively breast fed due to low vitamin K levels in breast milk and intestinal changes in bacterial flora. Oral vitamin K supplementation is a simple addition to routine CF treatment during infancy to prevent complications from significant coagulopathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Pharmacokinetics of meloxicam after intravenous, intramuscular, and oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

    PubMed

    Molter, Christine M; Court, Michael H; Cole, Gretchen A; Gagnon, David J; Hazarika, Suwagmani; Paul-Murphy, Joanne R

    2013-03-01

    To compare pharmacokinetics after IV, IM, and oral administration of a single dose of meloxicam to Hispaniolan Amazon parrots (Amazona ventralis). 11 healthy parrots. Cohorts of 8 of the 11 birds comprised 3 experimental groups for a crossover study. Pharmacokinetics were determined from plasma concentrations measured via high-performance liquid chromatography after IV, IM, and oral administration of meloxicam at a dose of 1 mg/kg. Initial mean ± SD plasma concentration of 17.3 ± 9.0 μg/mL was measured 5 minutes after IV administration, whereas peak mean concentration was 9.3 ± 1.8 μg/mL 15 minutes after IM administration. At 12 hours after administration, mean plasma concentrations for IV (3.7 ± 2.5 μg/mL) and IM (3.5 ± 2.2 μg/mL) administration were similar. Peak mean plasma concentration (3.5 ± 1.2 μg/mL) was detected 6 hours after oral administration. Absolute systemic bioavailability of meloxicam after IM administration was 100% but was lower after oral administration (range, 49% to 75%). Elimination half-lives after IV, IM, and oral administration were similar (15.9 ± 4.4 hours, 15.1 ± 7.7 hours, and 15.8 ± 8.6 hours, respectively). Pharmacokinetic data may provide useful information for use of meloxicam in Hispaniolan Amazon parrots. A mean plasma concentration of 3.5 μg/mL would be expected to provide analgesia in Hispaniolan Amazon parrots; however, individual variation may result in some birds having low plasma meloxicam concentrations after IV, IM, or oral administration. After oral administration, meloxicam concentration slowly reached the target plasma concentration, but that concentration was not sustained in most birds.

  14. Differential Effects of Oral and Intravenous Lipid Administration on Key Molecules Related to Energy Homeostasis

    PubMed Central

    Vamvini, Maria T.; Hamnvik, Ole-Petter; Sahin-Efe, Ayse; Gavrieli, Anna; Dincer, Fadime; Farr, Olivia M.

    2016-01-01

    Context: The spectrum of lipid-induced changes in the secretion of hormones important in energy homeostasis has not yet been fully elucidated. Objective: To identify potential incretin-like effects in response to lipid administration, we examined the short-term effect of iv vs oral lipids on key molecules regulating energy homeostasis. Design, Intervention, and Participants: After a 10-hour overnight fast, 26 subjects were randomized to receive an oral lipid load, a 10% iv lipid emulsion, a 20% iv lipid emulsion, or an iv saline infusion. We obtained blood samples at 30-minute intervals for the first 2 hours and hourly thereafter for a total of 6 hours. Main Outcome Measures: Circulating levels of insulin, glucose, c-peptide, free fatty acids, incretins (glucagon-like peptide-1, gastric inhibitory polypeptide), glucagon, peptide YY, ghrelin, fibroblast growth factor 21, fetuin A, irisin, omentin, and adiponectin were measured. Results: Oral lipid ingestion resulted in higher glucagon-like peptide-1, gastric inhibitory polypeptide, glucagon, and peptide YY levels, compared with the other three groups (incremental area under the curve P = .003, P < .001, P < .001, P < .001, respectively). The 20% lipid emulsion, leading to higher free fatty acid levels, resulted in greater insulin, c-peptide, and fibroblast growth factor 21 responses compared with placebo and the other two groups (incremental area under the curve P = .002, P = .005, P < .001, P < .001, respectively). Omentin, adiponectin, fetuin A, and irisin levels were not affected by either mode of lipid administration. Conclusions: Metabolic responses to lipids depend on the route of administration. Only iv lipids trigger a dose-dependent fibroblast growth factor 21 secretion, which is nonglucagon mediated. Intravenous lipids also induce hyperinsulinemia without concurrent decreases in glucose, a phenomenon observed in insulin-resistant states. Orally administered lipids mostly affect gastrointestinal tract

  15. Oral administration of erythrocyte membrane antigen does not suppress anti-Rh(D) antibody responses in humans.

    PubMed Central

    Barnes, R M; Duguid, J K; Roberts, F M; Risk, J M; Johnson, P M; Finn, R; Hardy, J; Napier, J A; Clarke, C A

    1987-01-01

    The effects of prior oral administration of erythrocyte membrane preparations (Oral Rh antigen) on the serum anti-Rh(D) antibody response has been evaluated in non-sensitized Rh(D)-negative male volunteers, and in female volunteers sensitized previously by Rh(D)-positive fetal blood during pregnancy. Sixty-one percent (11/18) of males who received oral Rh antigen (either D-positive or D-negative) before intravenous challenge with Rh(D)-positive cells produced detectable antibodies; of these 11, six received oral Rh(D)-negative antigen and five received oral Rh(D)-positive antigen. Seventy-two percent (13/18) of control males, who had received no prior oral Rh antigen, produced antibodies following challenge with Rh(D)-positive cells. Three out of six pre-sensitized females who received oral D-positive or D-negative Rh antigen for 4 weeks, but without intravenous challenge, increased their anti-Rh(D) antibody levels which peaked after 11-18 weeks: two had received Rh(D)-positive antigen, and one Rh(D)-negative antigen. These data indicate that administration of oral Rh antigen before parenteral immunization does not significantly suppress the anti-Rh(D) antibody response. Indeed, oral administration of either Rh(D)-positive or Rh(D)-negative antigen can boost systemic antibody in pre-sensitized females. These results do not support the rationale of treating Rh-sensitized pregnant women with oral Rh antigen. PMID:3113783

  16. Oral Administration of Interferon Tau Enhances Oxidation of Energy Substrates and Reduces Adiposity in Zucker Diabetic Fatty Rats

    PubMed Central

    Tekwe, Carmen D.; Lei, Jian; Yao, Kang; Rezaei, Reza; Li, Xilong; Dahanayaka, Sudath; Carroll, Raymond J.; Meininger, Cynthia J.; Bazer, Fuller W.; Wu, Guoyao

    2013-01-01

    Male Zucker diabetic fatty (ZDF) rats were used to study effects of oral administration of interferon tau (IFNT) in reducing obesity. Eighteen ZDF rats (28 days of age) were assigned randomly to receive 0, 4 or 8 μg IFNT/kg body weight (BW) per day (n=6/group) for 8 weeks. Water consumption was measured every two days. Food intake and BW were recorded weekly. Energy expenditure in 4-, 6-, 8-, and 10-week-old rats was determined using indirect calorimetry. Starting at 7 weeks of age, urinary glucose and ketone bodies were tested daily. Rates of glucose and oleate oxidation in liver, brown adipose tissue, and abdominal adipose tissue, leucine catabolism in skeletal muscle, and lipolysis in white and brown adipose tissues were greater for rats treated with 8 μg IFNT/kg BW/day in comparison with control rats. Treatment with 8 μg IFNT/kg BW/day increased heat production, reduced BW gain and adiposity, ameliorated fatty liver syndrome, delayed the onset of diabetes, and decreased concentrations of glucose, free fatty acids, triacylglycerol, cholesterol, and branched-chain amino acids in plasma, compared to control rats. Oral administration of 8 μg IFNT/kg BW/day ameliorated oxidative stress in skeletal muscle, liver and adipose tissue, as indicated by decreased ratios of oxidized glutathione to reduced glutathione and increased concentrations of the antioxidant tetrahydrobiopterin. These results indicate that IFNT stimulates oxidation of energy substrates and reduces obesity in ZDF rats and may have broad important implications for preventing and treating obesity-related diseases in mammals. PMID:23804503

  17. Oral Administration of Linoleic Acid Induces New Vessel Formation and Improves Skin Wound Healing in Diabetic Rats.

    PubMed

    Rodrigues, Hosana G; Vinolo, Marco A R; Sato, Fabio T; Magdalon, Juliana; Kuhl, Carolina M C; Yamagata, Ana S; Pessoa, Ana Flávia M; Malheiros, Gabriella; Dos Santos, Marinilce F; Lima, Camila; Farsky, Sandra H; Camara, Niels O S; Williner, Maria R; Bernal, Claudio A; Calder, Philip C; Curi, Rui

    2016-01-01

    Impaired wound healing has been widely reported in diabetes. Linoleic acid (LA) accelerates the skin wound healing process in non-diabetic rats. However, LA has not been tested in diabetic animals. We investigated whether oral administration of pure LA improves wound healing in streptozotocin-induced diabetic rats. Dorsal wounds were induced in streptozotocin-induced type-1 diabetic rats treated or not with LA (0.22 g/kg b.w.) for 10 days. Wound closure was daily assessed for two weeks. Wound tissues were collected at specific time-points and used to measure fatty acid composition, and contents of cytokines, growth factors and eicosanoids. Histological and qPCR analyses were employed to examine the dynamics of cell migration during the healing process. LA reduced the wound area 14 days after wound induction. LA also increased the concentrations of cytokine-induced neutrophil chemotaxis (CINC-2αβ), tumor necrosis factor-α (TNF-α) and leukotriene B4 (LTB4), and reduced the expression of macrophage chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1). These results together with the histological analysis, which showed accumulation of leukocytes in the wound early in the healing process, indicate that LA brought forward the inflammatory phase and improved wound healing in diabetic rats. Angiogenesis was induced by LA through elevation in tissue content of key mediators of this process: vascular-endothelial growth factor (VEGF) and angiopoietin-2 (ANGPT-2). Oral administration of LA hastened wound closure in diabetic rats by improving the inflammatory phase and angiogenesis.

  18. Renal, gastrointestinal, and hemostatic effects of oral administration of meloxicam to Hispaniolan Amazon parrots (Amazona ventralis).

    PubMed

    Dijkstra, Bas; Guzman, David Sanchez-Migallon; Gustavsen, Kate; Owens, Sean D; Hass, Carlyle; Kass, Philip H; Paul-Murphy, Joanne R

    2015-04-01

    To investigate renal, gastrointestinal, and hemostatic effects associated with oral administration of multiple doses of meloxicam to healthy Hispaniolan Amazon parrots (Amazona ventralis). 12 Hispaniolan Amazon parrots. Birds were assigned to receive meloxicam oral suspension (1.6 mg/kg, PO, q 12 h) and 2.5 mL of tap water inserted into the crop by use of a gavage tube (n = 8) or the equivalent volume of tap water only (control group; 4) for 15 days. Urine and feces were collected 2 hours after treatment administration each day. Feces were evaluated for occult blood. Results of a CBC and serum biochemical analysis and measured N-acetyl-β-d-glucosaminidase (NAG) activity and whole blood clotting time were evaluated before, during, and after completion of treatments. Results of urinalysis and measured urine NAG activity were also evaluated. Birds treated with meloxicam had a significant increase in number of WBCs and decrease in PCV from before to after treatment. The PCV also decreased significantly, compared with results for the control group; however, WBC count and PCV for all birds remained within reference ranges throughout the study. One parrot treated with meloxicam had a single high value for urine NAG activity. Meloxicam administered orally at the dosage used in this study caused no apparent negative changes in several renal, gastrointestinal, or hemostatic variables in healthy Hispaniolan Amazon parrots. Additional studies to evaluate adverse effects of NSAIDs in birds will be needed.

  19. [Effects of ranitidine on pharmacokinetics of rhein from Dachengqi Decoction in rats after oral administration].

    PubMed

    Ren, Yan-yi; Gong, Han-lin; Tang, Wen-fu; Wan, Mei-fua; Huang, Xi

    2009-09-01

    To explore the effects of ranitidine on pharmacokinetics of rhein in rats after oral administration of Dachengqi Decoction (DCQD), a compound traditional Chinese herbal medicine. Twelve male Sprague-Dawley rats were divided into DCQD group and DCQD plus ranitidine group, and were orally administered with DCQD at a dose of 10 g/kg or DCQD (10 g/kg) combined with ranitidine (150 mg/kg), respectively. Blood samples were gathered after a series of time intervals. Metabolism of rhein was determined with a reversed-phase high-performance liquid chromatography with internal standard of 1, 8-dihydroxyanthraquinone and the data were analyzed with DAS 2.1 program. The pharmacokinetic parameters were compared between the two groups. The pharmacokinetic parameters of rhein in the DCQD group, including peak concentration (C(max)), area under the plasma concentration-time curve (AUC), distribution phase half-life (t(1/2alpha)), elimination rate constant (K(10)) and central to peripheral transfer rate constant (K(12)), were significantly different to those in the DCQD plus ranitidine group (P<0.05, P<0.01). There were no significant differences in the other parameters between the two groups. Ranitidine can influence the pharmacokinetics of rhein in rats after oral administration of DCQD.

  20. Pharmacokinetics of enrofloxacin following oral and subcutaneous administration in the common ringtail possum (Pseudocheirus peregrinus).

    PubMed

    Scheelings, T F; Devi, J L; Woodward, A P; Whittem, T

    2015-10-01

    [Correction added on 23 March 2015, after first online publication: Terminal half-life values of enrofloxacin is corrected in the fourth sentence of the abstract] Clinically healthy common ringtail possums (n = 5) received single doses of 10 mg/kg enrofloxacin orally and then 2 weeks later subcutaneously. Serial plasma samples were collected over 24 h for each treatment phase, and enrofloxacin concentrations were determined using a validated HPLC assay. Pharmacokinetic parameters were determined by noncompartmental analysis. Following oral administration, plasma concentrations were of therapeutic relevance (Cmax median 5.45 μg/mL, range 2.98-6.9 μg/mL), with terminal-phase half-life (t½ ) shorter than in other species (median 3.09 h, range 1.79-5.30 h). In contrast, subcutaneous administration of enrofloxacin did not achieve effective plasma concentrations, with plasma concentrations too erratic to fit the noncompartmental model except in one animal. On the basis of the AUC:MIC, enrofloxacin administered at 10 mg/kg orally, but not subcutaneously, is likely to be effective against a range of bacterial species that have been reported in common ringtail possums. © 2015 John Wiley & Sons Ltd.

  1. Improved oral bioavailability and brain transport of Saquinavir upon administration in novel nanoemulsion formulations.

    PubMed

    Vyas, Tushar K; Shahiwala, Aliasgar; Amiji, Mansoor M

    2008-01-22

    The aim of this investigation was to develop novel oil-in-water (o/w) nanoemulsions containing Saquinavir (SQV), an anti-HIV protease inhibitor, for enhanced oral bioavailability and brain disposition. SQV was dissolved in different types of edible oils rich in essential polyunsaturated fatty acids (PUFA) to constitute the internal oil phase of the nanoemulsions. The external phase consisted of surfactants Lipoid-80 and deoxycholic acid dissolved in water. The nanoemulsions with an average oil droplet size of 100-200 nm, containing tritiated [(3)H]-SQV, were administered orally and intravenously to male Balb/c mice. The SQV bioavailability as well as distribution in different organ systems was examined. SQV concentrations in the systemic circulation administered in flax-seed oil nanoemulsions were threefold higher as compared to the control aqueous suspension. The oral bioavailability and distribution to the brain, a potential sanctuary site for HIV, were significantly enhanced with SQV delivered in nanoemulsion formulations. In comparing SQV in flax-seed oil nanoemulsion with aqueous suspension, the maximum concentration (C(max)) and the area-under-the-curve (AUC) values were found to be five- and threefold higher in the brain, respectively, suggesting enhanced rate and extent of SQV absorption following oral administration of nanoemulsions. The results of this study show that oil-in-water nanoemulsions made with PUFA-rich oils may be very promising for HIV/AIDS therapy, in particular, for reducing the viral load in important anatomical reservoir sites.

  2. Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration.

    PubMed

    Harigae, Takahiro; Nakagawa, Kiyotaka; Miyazawa, Taiki; Inoue, Nao; Kimura, Fumiko; Ikeda, Ikuo; Miyazawa, Teruo

    2016-01-01

    Curcumin (CUR), the main polyphenol in turmeric, is poorly absorbed and rapidly metabolized following oral administration, which severely curtails its bioavailability. Poly-(lactic-co-glycolic acid)-based CUR nanoparticles (CUR-NP) have recently been suggested to improve CUR bioavailability, but this has not been fully verified. Specifically, no data are available about curcumin glucuronide (CURG), the major metabolite of CUR found in the plasma following oral administration of CUR-NP. Herein, we investigated the absorption and metabolism of CUR-NP and evaluated whether CUR-NP improves CUR bioavailability. Following oral administration of CUR-NP in rats, we analyzed the plasma and organ distribution of CUR and its metabolites using high-performance liquid chromatography-tandem mass spectrometry. To elucidate the mechanism of increased intestinal absorption of CUR-NP, we prepared mixed micelles comprised of phosphatidylcholine and bile salts and examined the micellar solubility of CUR-NP. Additionally, we investigated the cellular incorporation of the resultant micelles into differentiated Caco-2 human intestinal cells. Following in vivo administration of CUR-NP, CUR was effectively absorbed and present mainly as CURG in the plasma which contained significant amounts of the metabolite compared with other organs. Thus, CUR-NP increased intestinal absorption of CUR rather than decreasing metabolic degradation and conversion to other metabolites. In vitro, CUR encapsulated in CUR-NP was solubilized in mixed micelles; however, whether the micelles contained CUR or CUR-NP had little influence on cellular uptake efficiency. Therefore, we suggest that the high solubilization capacity of CUR-NP in mixed micelles, rather than cellular uptake efficiency, explains the high intestinal absorption of CUR-NP in vivo. These findings provide a better understanding of the bioavailability of CUR and CUR-NP following oral administration. To improve the bioavailability of CUR, future

  3. Pharmacokinetics of oral neratinib during co-administration of ketoconazole in healthy subjects.

    PubMed

    Abbas, Richat; Hug, Bruce A; Leister, Cathie; Burns, Jaime; Sonnichsen, Daryl

    2011-04-01

    The primary objective was to evaluate the pharmacokinetics of a single dose of neratinib, a potent, low-molecular-weight, orally administered, irreversible pan-ErbB (ErbB-1, -2, -4) receptor tyrosine kinase inhibitor, during co-administration with ketoconazole, a potent CYP3A4 inhibitor. This was an open-label, randomized, two-period, crossover study. Fasting healthy adults received a single oral dose of neratinib 240 mg alone and with multiple oral doses of ketoconazole 400 mg. Blood samples were collected up to 72 h after each neratinib dose. Plasma concentration data were analyzed using a noncompartmental method. The least square geometric mean ratios [90% confidence interval (CI)] of C(max) (neratinib+ketoconazole): C(max) (neratinib alone), and AUC(neratinib+ketoconazole): AUC(neratinib alone) were assessed. Twenty-four subjects were enrolled. Compared with neratinib administered alone, co-administration of ketoconazole increased neratinib C(max) by 3.2-fold (90% CI: 2.4, 4.3) and AUC by 4.8-fold (3.6, 6.5). Median t(max) was 6.0 h with both regimens. Ketoconazole decreased mean apparent oral clearance of neratinib from 346 lh(-1) to 87.1 lh(-1) and increased mean elimination half-life from 11.7 h to 18.0 h. The incidence of adverse events was comparable between the two regimens (50% neratinib alone, 65% co-administration with ketoconazole). Co-administration of neratinib with ketoconazole, a potent CYP3A inhibitor, increased neratinib C(max) by 3.2-fold and AUC by 4.8-fold compared with administration of neratinib alone. These results indicate that neratinib is a substrate of CYP3A and is susceptible to interaction with potent CYP3A inhibitors and, thus, dose adjustments may be needed if neratinib is administered with such compounds. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

  4. A phase I and pharmacokinetic study of a powder-filled capsule formulation of oral irinotecan (CPT-11) given daily for 5 days every 3 weeks in patients with advanced solid tumors.

    PubMed

    Pitot, Henry C; Adjei, Alex A; Reid, Joel M; Sloan, Jeff A; Atherton, Pamela J; Rubin, Joseph; Alberts, Steven R; Duncan, Barbara A; Denis, Louis; Schaaf, Larry J; Yin, Donghua; Sharma, Amarnath; McGovren, Patrick; Miller, Langdon L; Erlichman, Charles

    2006-08-01

    Intravenous (i.v.) irinotecan is a cytotoxic topoisomerase I inhibitor with broad clinical activity in metastatic colorectal cancer and other tumors. The development of an oral formulation of irinotecan could enhance convenience and lessen the expense of palliative irinotecan delivery. This phase I study evaluated the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and pharmacokinetics (PK) of irinotecan given as a powder-filled capsule (PFC) daily for 5 days every 3 weeks. Patients with advanced solid tumors received escalating doses of oral irinotecan daily for 5 days every 3 weeks. Plasma samples were collected following the first and fifth doses of irinotecan during Cycle 1 to determine the PK of irinotecan and its major circulating metabolites: SN-38, SN-38G, and APC. 20 patients (median age 61.5 years, range 40-75; M/F 12/8; ECOG PS 0=5, 1=11, 2=4) received oral irinotecan at dose levels of 30 (n=3), 40 (n=3), 50 (n=6), and 60 (n=8) mg/m(2)/day. Of the eight patients enrolled at 60 mg/m(2), three patients experienced DLT (> or = grade 3) consisting of nausea (three patients), vomiting (three patients), diarrhea (two patients), and febrile neutropenia (two patients) for which all the three patients required hospitalization. Treatment of six patients at the 50-mg/m(2) dose level resulted in no DLT. Other toxicities observed include abdominal pain, alopecia, anorexia, and asthenia. After oral administration, irinotecan was rapidly absorbed into systemic circulation and converted to the active metabolite SN-38. Increasing dose levels resulted in a dose-dependent increase in mean exposure parameters (Cmax and AUC) of irinotecan and metabolites. Systemic exposure parameters (Cmax and AUC(0-24)) of irinotecan and SN-38 were comparable between days 1 and 5. The extent of conversion from irinotecan to SN-38 was approximately threefold higher after the oral administration compared to that previously observed after i.v. administration. The exposure

  5. Withdrawal times of oxytetracycline and tylosin in eggs of laying hens after oral administration.

    PubMed

    Muñoz, Rubén; Cornejo, Javiera; Maddaleno, Aldo; Araya-Jordán, Carolina; Iragüen, Daniela; Pizarro, Nicolás; San Martín, Betty

    2014-06-01

    Antimicrobials administered to laying hens may be distributed into egg white or yolk, indicating the importance of evaluating withdrawal times (WDTs) of the pharmaceutical formulations. In the present study, oxytetracycline and tylosin's WDTs were estimated. The concentration and depletion of these molecules in eggs were linked to their pharmacokinetic and physicochemical properties. Twenty-seven Leghorn hens were used: 12 treated with oxytetracycline, 12 treated with tylosin, and 3 remained as an untreated control group. After completion of therapies, eggs were collected daily and drug concentrations in egg white and yolk were assessed. The yolk was used as the target tissue to evaluate the WDT; the results were 9 and 3 days for oxytetracycline and tylosin, respectively. In particular, oxytetracycline has a good oral bioavailability, a moderate apparent volume of distribution, a molecular weight of 460 g/mol, and is lightly liposoluble. Tylosin, a hydrosoluble compound, with a molecular weight of 916 g/mol, has a low oral bioavailability and a low apparent volume of distribution, too. Present results suggest that the WDTs of the studied antimicrobials are strongly influenced by their oral bioavailability, the distribution, and the molecular weight and solubility, and that these properties also influence the distribution between the egg yolk and white.

  6. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase.

    PubMed

    Sumi, H; Hamada, H; Nakanishi, K; Hiratani, H

    1990-01-01

    The existence of a potent fibrinolytic enzyme (nattokinase, NK) in the traditional fermented food called 'natto', was reported by us previously. It was confirmed that oral administration of NK (or natto) produced a mild and frequent enhancement of the fibrinolytic activity in the plasma, as indicated by the fibrinolytic parameters, and the production of tissue plasminogen activator. NK capsules were also administered orally to dogs with experimentally induced thrombosis, and lysis of the thrombi was observed by angiography. The results obtained suggest that NK represents a possible drug for use not only in the treatment of embolism but also in the prevention of the disease, since NK has a proven safety and can be massproduced.

  7. Excretion profile of boldenone and its metabolites after oral administration to veal calves.

    PubMed

    Ferretti, G; Palleschi, L; Marchiafava, C; delli Quadri, F; Fantozzi, L; Ferranti, C; Cammarata, P; Macrì, A; Montesissa, C; Draisci, R

    2007-04-25

    The residue profiles of boldenone (17beta-Bol), its epimer (17alpha-Bol) and the related compound androsta-1,4-diene-3,17-dione (ADD), were investigated by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in urine of male calves orally treated with boldenone, boldenone esters, and/or ADD. In all the experiments with the administered steroids residues of 17alpha-Bol decreased rapidly after end of treatment; detectable amounts of 17alpha-Bol were however noticed along the withdrawal observation period after end of treatment. Differently, residues of 17beta-Bol were detectable only shortly after administration. This in vivo research concerning oral treatments of cattle with boldenone related substances proves ADD to be a very active boldenone precursor in bovine animals.

  8. Pharmacokinetics of flunixin meglumine in mature swine after intravenous, intramuscular and oral administration

    PubMed Central

    2013-01-01

    Background The purpose of this study was to determine intravenous (IV), intramuscular (IM) and oral (PO) FM PK in mature swine. Appropriate pain management for lameness in swine is a critical control point for veterinarians and producers, but science-based guidance on optimal housing, management and treatment of lameness is deficient. Six mature swine (121–168 kg) were administered an IV, IM, or PO dose of flunixin meglumine at a target dose of 2.2 mg/kg in a cross-over design with a 10 day washout period between treatments. Plasma samples collected up to 48 hours post-administration were analyzed by high pressure liquid chromatography and mass spectrometry (HPLC-MS) followed by non-compartmental pharmacokinetic analysis. Results No adverse effects were observed with flunixin meglumine administration for all routes. Flunixin meglumine was administered at an actual mean dose of 2.21 mg/kg (range: 2.05-2.48 mg/kg) IV, IM and PO. A mean peak plasma concentration (CMAX) for IM and PO administration was 3748 ng/ml (range: 2749–6004 ng/ml) and 946 ng/ml (range: 554–1593 ng/ml), respectively. TMAX was recorded at 1.00 hour (range: 0.50-2.00 hours) and 0.61 hours (range: 0.17-2.00 hours) after PO and IM administration. Half-life (T ½ λz) for IV, IM and PO administration was 6.29 hours (range: 4.84-8.34 hours), 7.49 hours (range: 5.55-12.98 hours) and 7.08 hours (range: 5.29-9.15 hours) respectively. In comparison, bioavailability (F) for PO administration was 22% (range: 11-44%) compared to IM F at 76% (range: 54-92%). Conclusions The results of the present study suggest that FM oral administration is not the most effective administration route for mature swine when compared to IV and IM. Lower F and Cmax of PO-FM in comparison to IM-FM suggest that PO-FM is less likely to be an effective therapeutic administration route. PMID:23941181

  9. Templates of patient brochures for the preparation, administration and safe-handling of oral chemotherapy.

    PubMed

    Siden, Rivka; Kem, Ravie; Ostrenga, Andrew; Nicksy, Darcy; Bernhardt, Brooke; Bartholomew, Joy

    2014-06-01

    The increased use of oral chemotherapy for the treatment of cancer introduces new challenges for patients and caregivers. Among them are the ability to swallow oral solid dosage forms, the proper administration of the agents and the safe-handling of chemotherapeutic drugs in the home. Since these drugs are hazardous, proper preparation, administration, and disposition introduces a variety of safety issues. The increased toxicity of these drugs coupled with complicated dosing regimens and the occasional need to dilute the drug or measure a liquid dosage form require careful instruction of the patient and/or caregivers. The purpose of this project was to create templates for writing patient instruction brochures. A group of clinicians specializing in oncology from several institutions in the United States and Canada met through a series of conference calls. The group included pharmacists with a specialty in pediatric oncology, investigational drug pharmacists, and an oncology nurse practitioner. National guidelines and practices at each institution were used for the creation of templates to be used in developing templates for medication and formulation-specific instruction brochures. The group developed six templates. The templates ranged in scope from instructions on the administration of intact tablets or capsules to directions on opening capsules or crushing tablets and mixing the content with foods or liquids. Thirty-three drug-specific brochures were developed using the templates. Templates of patient brochures and drug-specific brochures on the safe handling of chemotherapy in the home can be created using a collaborative, multi-institutional approach.

  10. Oral administration of aflatoxin G₁ induces chronic alveolar inflammation associated with lung tumorigenesis.

    PubMed

    Liu, Chunping; Shen, Haitao; Yi, Li; Shao, Peilu; Soulika, Athena M; Meng, Xinxing; Xing, Lingxiao; Yan, Xia; Zhang, Xianghong

    2015-02-03

    Our previous studies showed oral gavage of aflatoxin G₁ (AFG₁) induced lung adenocarcinoma in NIH mice. We recently found that a single intratracheal administration of AFG₁ caused chronic inflammatory changes in rat alveolar septum. Here, we examine whether oral gavage of AFG₁ induces chronic lung inflammation and how it contributes to carcinogenesis. We evaluated chronic lung inflammatory responses in Balb/c mice after oral gavage of AFG₁ for 1, 3 and 6 months. Inflammatory responses were heightened in the lung alveolar septum, 3 and 6 months after AFG₁ treatment, evidenced by increased macrophages and lymphocytes infiltration, up-regulation of NF-κB and p-STAT3, and cytokines production. High expression levels of superoxide dismutase (SOD-2) and hemoxygenase-1 (HO-1), two established markers of oxidative stress, were detected in alveolar epithelium of AFG₁-treated mice. Promoted alveolar type II cell (AT-II) proliferation in alveolar epithelium and angiogenesis, as well as increased COX-2 expression were also observed in lung tissues of AFG₁-treated mice. Furthermore, we prolonged survival of the mice in the above model for another 6 months to examine the contribution of AFG₁-induced chronic inflammation to lung tumorigenesis. Twelve months later, we observed that AFG₁ induced alveolar epithelial hyperplasia and adenocarcinoma in Balb/c mice. Up-regulation of NF-κB, p-STAT3, and COX-2 was also induced in lung adenocarcinoma, thus establishing a link between AFG₁-induced chronic inflammation and lung tumorigenesis. This is the first study to show that oral administration of AFG₁ could induce chronic lung inflammation, which may provide a pro-tumor microenvironment to contribute to lung tumorigenesis. Copyright © 2014. Published by Elsevier Ireland Ltd.

  11. Absorption of Bupivacaine after Administration of a Lozenge as Topical Treatment for Pain from Oral Mucositis.

    PubMed

    Mogensen, Stine; Sverrisdóttir, Eva; Sveinsdóttir, Kolbrún; Treldal, Charlotte; Jensen, Kenneth; Jensen, Anders Bonde; Kristensen, Claus Andrup; Jacobsen, Jette; Kreilgaard, Mads; Petersen, Janne; Andersen, Ove

    2017-01-01

    The aim was to investigate systemic exposure after administration of a novel bupivacaine lozenge in healthy individuals with normal mucosa and in head and neck cancer (HNC) patients with oral mucositis. A lozenge containing 5, 10, 25 and 50 mg bupivacaine, respectively, was administered as single dose to 10 healthy individuals, and a lozenge containing 25 mg bupivacaine was administered as single dose to 10 HNC patients with oral mucositis and as multiple doses to five patients with HNC. Blood samples were collected for 6 hr from the healthy individuals and 3 hr from the patients with HNC, respectively, after administration. The plasma concentration-time profiles of bupivacaine were fitted to pharmacokinetic models using nonlinear mixed-effects modelling, evaluating demographics and health status as covariates. The population pharmacokinetics (PK) of bupivacaine lozenge was best described by a two-compartment distribution model with absorption transit compartments. All the observed plasma concentrations were well below the bupivacaine concentrations (2000-2250 ng/ml) which have caused toxic symptoms. The PK model suggested that relative bioavailability was two times higher in HNC patients with oral mucositis grade 1-2 and three times higher in HNC patients with oral mucositis grade 3-4 than in the healthy individuals. Simulations showed that the plasma concentrations would be below the toxic limit after repeated dosing every second hour with 25 mg bupivacaine for five days. The 25-mg bupivacaine lozenges were safe without systemic toxic levels of bupivacaine or risk of side effects. Based on PK simulations of repeated doses of 25 mg every two hours for 16 hr a day, the lozenges can be administered with minimum risk of exceeding the toxic limit. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  12. Comparative pharmacokinetics of arctigenin in normal and type 2 diabetic rats after oral and intravenous administration.

    PubMed

    Zeng, Xiao-yan; Dong, Shu; He, Nan-nan; Jiang, Chun-jie; Dai, Yue; Xia, Yu-feng

    2015-09-01

    Arctigenin is the main active ingredient of Fructus Arctii for the treatment of type 2 diabetes. In this study, the pharmacokinetics of arctigenin in normal and type 2 diabetic rats following oral and intravenous administration was investigated. As compared to normal rats, Cmax and AUC(0-10h) values of oral arctigenin in diabetic rats increased by 356.8% and 223.4%, respectively. In contrast, after intravenous injection, the Cmax and AUC(0-10h) values of arctigenin showed no significant difference between diabetic and normal rats. In order to explore how the bioavailability of oral arctigenin increased under diabetic condition, the absorption behavior of arctigenin was evaluated by in situ single-pass intestinal perfusion (SPIP). The results indicated that arctigenin was a substrate of P-glycoprotein (P-gp). The absorption difference of arctigenin in the normal and diabetic rats could be eliminated by the pretreatment of classic P-gp inhibitor verapamil, suggesting that P-gp might be the key factor causing the absorption enhancement of arctigenin in diabetic rats. Further studies revealed that the uptake of rhodamine 123 (Rho123) in diabetic rats was significantly higher, indicating that diabetes mellitus might impair P-gp function. Consistently, a lower mRNA level of P-gp in the intestine of diabetic rats was found. In conclusion, the absorption of arctigenin after oral administration was promoted in diabetic rats, which might be partially attribute to the decreased expression and impaired function of P-gp in intestines. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Making the leap from daily oral dosing to long-acting injectables: lessons from the antipsychotics.

    PubMed

    Remenar, Julius F

    2014-06-02

    There are now long-acting versions of six antipsychotic drugs on the U.S. market, and with them, five unique combinations of molecular form and delivery strategy long-acting-injectable-antipsychotics (LAIAs) show evidence of reduced relapses of schizophrenia, but their introduction has been slow, taking at least nine years after the approval of each oral drug. Oily solutions of lipophilic prodrugs were the first to enter the LAIA market, but they relied on esterification of a hydroxyl handle that was lost with the emergence of the atypical antipsychotics. A review of the literature and patents shows that companies tested many different approaches before reaching the currently marketed versions, including aqueous suspensions of poorly soluble salts, polymeric microspheres, and new approaches to making prodrugs. Yet, very little has been published to support faster development of safe long-acting injectables (LAIs). This review introduces some of the critical considerations in creating an LAI; then it analyzes the existing products and discusses areas where further research is needed. The available literature suggests that lipophilic prodrugs may be inherently safer than poorly soluble salts as LAIs. Other areas needing additional study include (1) the range of physical properties acceptable for LAIs and the effect of prodrug tail length in achieving them, and (2) the role of physiological responses at the injection site in the release of drug from a depot.

  14. Oral administration of antimicrobials increase antimicrobial resistance in E. coli from chicken--a systematic review.

    PubMed

    Simoneit, C; Burow, E; Tenhagen, B-A; Käsbohrer, A

    2015-01-01

    Antimicrobials play an important role in animal and human health care. It was the aim of this systematic review to assess the effects of oral administration of antimicrobials on the development of antimicrobial resistance (AMR) in Escherichia coli (E. coli) from chickens. Moreover, the effects of the administration of more than one antimicrobial and of different dosages were studied. Literature was searched in November 2012 from the electronic databases ISI Web of Science, PubMed, Scopus and a national literature database (DIMDI) as well as the database ProQuest LLC. The search was updated in March 2014. Original studies describing a treatment (A) and a control group of either non-treatment (C) or initial value (0) and determining AMR in E. coli at different sample points (SP) were included. The literature search resulted in 35 full text articles on the topic, seven (20%) of which contained sufficient information on the administered antimicrobial and the impact of treatment on AMR. Most papers described the use of more than one antimicrobial, several dosages, controls (non-treatment or pre-treatment) and measured AMR at different SPs leading to a total of 227 SPs on the impact of the use of antimicrobials on AMR in chickens. 74% of the SPs (168/227) described a higher AMR-rate in E. coli from treated animals than from controls. After the administration of a single antimicrobial, AMR increased at 72% of the SPs. Administration of more than one antimicrobial increased AMR at 82% of the SPs. Higher dosages were associated with similar or higher AMR rates. The limited number of studies for each antimicrobial agent and the high variability in the resistance effect call for more well designed studies on the impact of oral administration on AMR development and spread. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Pharmacokinetics of mequindox and its metabolites in rats after intravenous and oral administration.

    PubMed

    Li, Guanghui; Yang, Fan; He, Limin; Ding, Huanzhong; Sun, Na; Liu, Yingchun; Liu, Yiming; Shan, Qi; Li, Yafei; Zeng, Zhenling

    2012-12-01

    Pharmacokinetics of mequindox (MEQ) and its metabolites were determined in rats after intravenous (i.v.) and oral (p.o.) administration of MEQ at a single dose of 10 mg kg(-1) bodyweight. After both administrations, MEQ and five of its metabolites were quantified, except M4, whereas M1 and M2 were the predominant ones. The areas under the concentration-time curves (h ng mL(-1)) of MEQ, M1, M2, M3, M5 and M10 after i.v. administration were 7559±495, 6354±2761, 5586±2337, 1034±160, 2370±791 and 1813±622, respectively, whereas after p.o. administration, remained as 2809±40, 4361±3544, 4351±1046, 1444±814, 3864±305 and 1213±569, respectively. The elimination half-lives (h) of these compounds after i.v. administration were 3.48±0.80, 4.20±0.76, 6.25±2.41, 4.77±1.54, 4.69±1.62 and 16.89±5.15, respectively, and were 3.21±0.40, 3.66±1.06, 4.20±1.03, 8.91±5.99, 4.20±2.02 and 20.84±10.85 after p.o. administration, respectively. After p.o. administration, the bioavailability of MEQ was 37.16%. The results showed that MEQ was extensively metabolized in rats and rapidly absorbed after p.o. administration. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Effects of Oral Prednisone Administration on Serum Cystatin C in Dogs.

    PubMed

    Muñoz, J; Soblechero, P; Duque, F J; Macías-García, B; Ruiz, P; Zaragoza, C; Barrera, R

    2017-11-01

    Oral administration of glucocorticoid alters serum cystatin C (sCysC) concentration in humans. To determine if oral administration of prednisone alters sCysC in dogs without pre-existing renal disease. Forty six dogs were included: 10 dogs diagnosed with steroid responsive meningitis arteritis (SRMA; group A), 20 dogs diagnosed of pituitary-dependent hyperadrenocorticism (PDH; group B), and 16 healthy control dogs (group C). Retrospective observational study. SRMA diagnosed dogs were administered prednisone 4 mg/kg/24 h PO 7 days, reducing the dose to 2 mg/kg/24 h 7 days before medication withdrawal. In group A, sampling was performed at days 0, 7, 14 and a final control at day 21. Blood and urine samples were collected in the 3 groups, and in group A, sampling was performed at all time points (days 1, 7, 14, and 21). In group A, sCysC was significantly higher at day 7 compared to the control group (0.4 ± 0.04 mg/L vs. 0.18 ± 0.03 mg/L mean ± SEM respectively P < 0.01); sCysC values decreased to basal at day 14 when the dose was decreased and after 1 week of withdrawal of prednisone (0.27 ± 0.03 mg/L for group A at day 14 and 0.15 ± 0.02 mg/L at day 21; P > 0.05). Dogs with PDH included in group B did not have significant differences in sCysC (0.22 ± 0.03 mg/L) compared to control (P > 0.05). Oral administration of prednisone unlike altered endogenous glucocorticoid production, increases sCysC in dogs in a dose-dependent fashion. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  17. Experimental study of biological effects of leads and aluminum following oral administration.

    PubMed Central

    Krasovskiĭ, G N; Vasukovich, L Y; Chariev, O G

    1979-01-01

    A wide spectrum of the biological effects of lead and aluminum ions is noted during short-term and long-term oral administration to laboratory animals. The general toxic and gonadotoxic effects of these metals during a short-term experiment appeared to be identical, and the correlation of these effects was preserved during chronic experiments. Lead (0.03 mg/l.) and aluminum (0.5 mg/l.) concentrations in water may be dangerous to the health of the population, and hygienic standards are recommended for inclusion in the standard for drinking water quality. PMID:446457

  18. Oral fluid and plasma 3,4-methylenedioxymethamphetamine (MDMA) and metabolite correlation after controlled oral MDMA administration.

    PubMed

    Desrosiers, Nathalie A; Barnes, Allan J; Hartman, Rebecca L; Scheidweiler, Karl B; Kolbrich-Spargo, Erin A; Gorelick, David A; Goodwin, Robert S; Huestis, Marilyn A

    2013-05-01

    Oral fluid (OF) offers a noninvasive sample collection for drug testing. However, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) in OF has not been adequately characterized in comparison to plasma. We administered oral low-dose (1.0 mg/kg) and high-dose (1.6 mg/kg) MDMA to 26 participants and collected simultaneous OF and plasma specimens for up to 143 h after dosing. We compared OF/plasma (OF/P) ratios, time of initial detection (t first), maximal concentrations (C max), time of peak concentrations (t max), time of last detection (t last), clearance, and 3,4-methylenedioxyamphetamine (MDA)-to-MDMA ratios over time. For OF MDMA and MDA, C max was higher, t last was later, and clearance was slower compared to plasma. For OF MDA only, t first was later compared to plasma. Median (range) OF/P ratios were 5.6 (0.1-52.3) for MDMA and 3.7 (0.7-24.3) for MDA. OF and plasma concentrations were weakly but significantly correlated (MDMA: R(2) = 0.438, MDA: R(2) = 0.197, p < 0.0001). Median OF/P ratios were significantly higher following high dose administration: MDMA low = 5.2 (0.1-40.4), high = 6.0 (0.4-52.3, p < 0.05); MDA low = 3.3 (0.7-17.1), high = 4.1 (0.9-24.3, p < 0.001). There was a large inter-subject variation in OF/P ratios. The MDA/MDMA ratios in plasma were higher than those in OF (p < 0.001), and the MDA/MDMA ratios significantly increased over time in OF and plasma. The MDMA and MDA concentrations were higher in OF than in plasma. OF and plasma concentrations were correlated, but large inter-subject variability precludes the estimation of plasma concentrations from OF.

  19. Effects of oral administration of energy drinks on blood chemistry, tissue histology and brain acetylcholine in rabbits.

    PubMed

    Ebuehi, O A T; Ajayl, O E; Onyeulor, A L; Awelimobor, D

    2011-01-01

    Energy drinks are canned or bottled carbonated beverages that contain large amounts of caffeine and sugar with additional ingredients, such as B-Vitamins, amino acids and herbal stimulants. Previous reports have shown that consumption of large amounts of these energy drinks may result in adverse health consequences. The present study is to ascertain if oral administration of energy drinks, such as "power horse" and "red bull", may affect blood chemistry, tissue histology and acetyl choline levels in rabbits. Five ml of power horse and red bull energy drinks, caffeine and saline (control) were orally administered daily for 36 days to rabbits. Body weight, feed and water intake were measured every other day. The blood samples were taken by cardiac puncture for blood chemistry measurement and their liver, heart and brain tissues were used for histological assay. The plasma, liver, brain and heart acetylcholine levels were also determined. There were no significant differences in the body weight, feed intake and organ weights of rabbits administered energy drinks or caffeine as compared to the control. The blood chemistry results showed that the activities of the aspartate and alanine amino transferase, concentrations of plasma creatinine, uric acid and albumin were increased in the control as compared to the red bull and caffeine administered rabbits. The concentrations of total protein, total cholesterol, triglyceride, high density lipoprotein (HDL) and low density lipoprotein (LDL) and glucose concentrations were increased in power horse and red bull administered rabbits as compared to caffeine administered rabbits and control rabbits. The concentrations of plasma and brain acetylcholine of rabbits administered power horse and red bull were significantly higher than in the control, while it was lower in liver and heart acetyl choline levels. The histopathological findings of the brain and liver show that there were no obvious histopathological abnormalities in the

  20. Bioavailability of diazepam after intravenous, oral and rectal administration in adult epileptic patients.

    PubMed Central

    Dhillon, S; Oxley, J; Richens, A

    1982-01-01

    1 The absorption of single doses of diazepam in six adult epileptic subjects following intravenous, oral and rectal administration were studied in order to evaluate the usefulness of the latter in emergency situations in the adult. 2 Diazepam tablets (Valium, Roche) and rectal solution (Valium solution for intravenous administration) produced similar peak serum concentrations after delays of 15-90 min. 3 Two suppository formulations showed statistically significant differences in absorption characteristics. 4 Serum diazepam levels above 400 ng ml-1 (suggested to be necessary for a satisfactory anticonvulsant effect) were reached in only a few subjects after rectal doses of 10-20 mg of solution, and then usually after a delay of over 2 h. PMID:7059446

  1. [Comparative pharmacokinetics of paracetamol in humans following single oral and rectal administration (author's transl)].

    PubMed

    Liedtke, R; Berner, G; Haase, W; Nicolai, W; Staab, R; Wagener, H H

    1979-01-01

    The pharmacokinetic behaviour of N-acetyl-p-aminophenol (paracetamol) after single dose applications of 500 mg and 1000 mg dosages in the form of liquids, tablets and suppositories was compared. The estimation of the pharmacokinetic constants by a simultaneous curve fitting with a direct search procedure, based on an open two-compartment model, showed for the liquid as well as for the tablet formulation a good conformable and dosage proportional behaviour of the relative bioavailability. In opposite to the oral application, the suppositories had a significantly reduced invasion kinetics with a comparable elimination kinetics characterized by a lowering of Cmax and an increase of Tmax-values with comparable AUCs. The calculation of collapse-coefficients showed, with the exception of one suppository formulation, for all administrations a pharmacokinetic behaviour deviating from an open one-compartment model. The clinical consequences resulting from the pharmacokinetic behaviour of the different galenic formulations and routes of administrations are discussed.

  2. A 5-month toxicity study of the ethanol extract of the leaves of Heliotropium indicum in Sprague Dawley rats after oral administration.

    PubMed

    Owolabi, M A; Oribayo, O O; Ukpo, G E; Mbaka, G O; Akindehin, O E

    2015-01-01

    Heliotropium indicum Linn. (Boraginaceae) is used in Nigerian traditional medicine to treat tuberculosis with treatment lasting for 3 months; however, information on its toxicity is scarce. This study investigated the safety of the leaves of Heliotropium indicum after a 5 month oral administration. The leaves of H. indicum were dried; extracted in 70% ethanol and concentrated to dryness. Swiss mice were administered orally with single doses of the extract (0.5 to 12.0 g/kg b.wt /day); mortality was examined for up to 14 days. In another study, the plant material (0.5 to 2.0 g/kg b.wt /day) were administered daily by oral gavage to Sprague Dawley rats. Body weight was monitored weekly, hematological, biochemical and organ parameters were determined at the end of the 1st, 2nd and 5th months of extract administration. The oral administration of the ethanol extract of H. indicum caused dose-dependent mortality. The LD50 was 9.78 g/kg b.wt for the Swiss mice; no harmful effect was observed on the liver and kidney except the testes which exhibited considerable inflammatory changes at the highest dose of 2.0 g/kg b.wt./day after the 5th month treatment. No significant difference (P>0.05) was shown in the enzyme study, marginal increase occurred in some haematological parameters. The increase in body weight of the treated rats after its initial reduction was consistent and significantly different (P<0.05) from their initial body weight. Prolonged administration of the crude leaf extract of H. indicum is considered to be safe and nontoxic at the doses studied. However, there is a probability of a negative effect on the testes at a higher dose of the extract.

  3. Regulation of operant oral ethanol self-administration: a dose-response curve study in rats.

    PubMed

    Carnicella, Sebastien; Yowell, Quinn V; Ron, Dorit

    2011-01-01

    Oral ethanol self-administration procedures in rats are useful preclinical tools for the evaluation of potential new pharmacotherapies as well as for the investigation into the etiology of alcohol abuse disorders and addiction. Determination of the effects of a potential treatment on a full ethanol dose-response curve should be essential to predict its clinical efficacy. Unfortunately, this approach has not been fully explored because of the aversive taste reaction to moderate to high doses of ethanol, which may interfere with consumption. In this study, we set out to determine whether a meaningful dose-response curve for oral ethanol self-administration can be obtained in rats. Long-Evans rats were trained to self-administer a 20% ethanol solution in an operant procedure following a history of excessive voluntary ethanol intake. After stabilization of ethanol self-administration, the concentration of the solution was varied from 2.5 to 60% (v/v), and operant and drinking behaviors, as well as blood ethanol concentration (BEC), were evaluated following the self-administration of a 20, 40, and 60% ethanol solution. Varying the concentration of ethanol from 2.5 to 60% after the development of excessive ethanol consumption led to a typical inverted U-shaped dose-response curve. Importantly, rats adapted their level and pattern of responding to changes in ethanol concentration to obtain a constant level of intake and BEC, suggesting that their operant behavior is mainly driven by the motivation to obtain a specific pharmacological effect of ethanol. This procedure can be a useful and straightforward tool for the evaluation of the effects of new potential pharmacotherapies for the treatment of alcohol abuse disorders. Copyright © 2010 by the Research Society on Alcoholism.

  4. Sedative and antinociceptive effects of dexmedetomidine and buprenorphine after oral transmucosal or intramuscular administration in cats.

    PubMed

    Porters, Nathalie; Bosmans, Tim; Debille, Mariëlla; de Rooster, Hilde; Duchateau, Luc; Polis, Ingeborgh

    2014-01-01

    To compare sedation and antinociception after oral transmucosal (OTM) and intramuscular (IM) administration of a dexmedetomidine-buprenorphine combination in healthy adult cats. Randomized, 'blinded' crossover study, with 1 month washout between treatments. Six healthy neutered female cats, weighing 5.3-7.5 kg. A combination of dexmedetomidine (40 μg kg(-1) ) and buprenorphine (20 μg kg(-1) ) was administered by either the OTM (buccal cavity) or IM (quadriceps muscle) route. Sedation was measured using a numerical rating scale, at baseline and at various time points until 6 hours after treatment. At the same time points, analgesia was scored using a dynamic and interactive visual analogue scale, based on the response to an ear pinch, and by the cat's response to a mechanical stimulus exerted by a pressure rate onset device. Physiological and adverse effects were recorded, and oral pH measured. Signed rank tests were performed, with significance set at p < 0.05. Data are presented as median and range. There were no differences in sedation or antinociception scores between OTM and IM dosing at any of the time points. Nociceptive thresholds increased after both treatments but without significant difference between groups. Buccal pH remained between 8 and 8.5. Salivation was noted after OTM administration (n = 2) and vomiting after both OTM (n = 4), and IM (n = 3) dosing. In healthy adult cats, OTM administration of dexmedetomidine and buprenorphine resulted in comparable levels of sedation and antinociception to IM dosing. The OTM administration may offer an alternative route to administer this sedative-analgesic combination in cats. © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  5. Changes in oral ethanol self-administration patterns resulting from ethanol concentration manipulations.

    PubMed

    Slawecki, C J; Samson, H H

    1997-09-01

    A variety of initiation procedures have been used to develop oral ethanol consumption. Using the sucrose-substitution procedure, oral self-administration of ethanol-water solutions with ethanol concentrations as high as 40% can be initiated in food- and fluid-sated rats. An important question for these models is the relationship between ethanol concentration and self-administration patterns after initiation. This study examined the differential patterns of ethanol self-administration maintained by a range of ethanol solutions (10 to 30%) over a 5-week period, compared with rats maintained on 10% ethanol for 5 weeks. In 43 male Long Evans rats, the sucrose-substitution procedure was used to initiate responding maintained by 10% ethanol on a Fixed Ratio 4 schedule of reinforcement. The ethanol concentration presented was then increased to 30% in stepwise fashion and then returned to 10% [Ethanol Concentration Manipulation (ECM) group, n = 32], or 10% ethanol was maintained as the reinforcer for 5 weeks [Control (Con) group, n = 11]. Significant increases in ethanol intake and decreases in responding were associated with increased ethanol concentration. Although no overall differences in total session responding were observed in either group between week 1 and week 5 (10E vs. 10E), examination of changes in initial low responders of the ECM group revealed significant increases in responding that were not observed in the initial low responders of the Con group. Significant increases in momentary response rates were observed on both the ECM and Con groups, independent of the ethanol concentration presented. Increases in response rate in the ECM group were the result of increases in initial low rate and high rate responders; however, the increased response rates in the Con group were the result of increases only in the initial low rate responders. These data suggest that the ECM procedure can aid in the initiation of ethanol self-administration and may be particularly

  6. Oral metformin-ascorbic acid co-administration ameliorates alcohol-induced hepatotoxicity in rats.

    PubMed

    Adeneye, A A; Benebo, A S

    2007-01-01

    Alcoholic liver disease remains a major cause of liver failure worldwide with no available curative or prophylactic therapy as at present. High dose metformin is reported to ameliorate liver injuries in both human and animal models of acute and chronic alcoholic liver injuries. The aim of the present in vivo animal study was to determine whether metformin-ascorbic acid co-administration also prevents alcoholic hepatotoxicity in chronic alcohol exposure. In the present study, ameliorating effect of 200 mg/ kg/day of ascorbic acid (Asc), 500 mg/kg/day of metformin (Met) and their co-administration (Met-Asc) were investigated in 5 groups of 50% ethanol-treated male Wistar rats for 2 weeks of the experiment. The body weight of each rat was taken on days 1, 7, and 14 of the experiment, respectively. On day 15, fasted blood samples for plasma lipids and liver enzyme markers were collected via cardiac puncture from the rats under diethyl ether anaesthesia. Results showed that administration of graded oral doses of 50% ethanol for 14 days significantly (p<0.001) elevated the plasma liver enzymes--aspartate aminotransferase (AST), alanine aminotansferase (ALT) and alkaline phosphatase (ALP). Two weeks of ethanol treatment also induced alterations in the plasma triglycerides (PTG), total cholesterol (PTC), high density lipoprotein (HDL-c), and low density lipoprotein (LDL-c). However, these elevations were significantly (p<0.05) attenuated by Asc, Met, and Met-Asc after 14 days of oral treatment, with Met-Asc having higher significant (p<0.001) ameliorating effect than Asc alone but with comparative effect to that of Met alone. High dose metformin-ascorbic acid co-administration protected the liver against the deleterious effects of chronic high dose alcohol and the hepatoprotective effect of Met-Asc appeared to be due mainly to the metformin molecule of the drug combination. However, further studies would be required to evaluate the mechanisms underlying the observed

  7. Comparative single-dose pharmacokinetics of clonazepam following intravenous, intramuscular and oral administration to healthy volunteers.

    PubMed

    Crevoisier, C; Delisle, M C; Joseph, I; Foletti, G

    2003-01-01

    The objective was to assess the single-dose pharmacokinetics of clonazepam following i.m., p.o. and i.v. administration. In an open-label, three-way crossover study, 12 healthy volunteers were randomized to receive a single dose of 2 mg clonazepam either by the i.m., p.o. or i.v. route. Serial blood samples were collected up to 120 h after drug administration. Plasma concentrations of clonazepam were determined by electron-capture gas-liquid chromatography. The absorption rates of clonazepam after i.m. and p.o. administration of clonazepam were significantly different from each other, as reflected by the respective mean values of maximum plasma concentration (C(max) 11.0 vs. 14.9 ng.ml(-1)) and time to reach maximum concentration (t(max) 3.1 vs. 1.7 h). Secondary plasma peaks of clonazepam were observed in 9 volunteers after i.m. injection (C(max) 9.9 ng.ml(-1); t(max) 10.4 h). A comparison of the area under the plasma concentration-time curves (AUC) shows that the i.m. route is equivalent to the oral route (AUC(0- infinity ) 620 vs. 561 ng.h.ml(-1)). Clonazepam was almost completely absorbed after i.m. and p.o. administration, as shown by the mean absolute bioavailability of 93 and 90%, respectively. No significant differences existed between the elimination half-lives (i.v. 38.0 h; i.m. 43.6 h; p.o. 39.0 h). The average clearance and volume of distribution (V(Z)) were 55 ml.min(-1) and 180 liters, respectively. In conclusion, the observed differences in C(max) and t(max) after i.m. and p.o. administration were consistent with a slower absorption rate of clonazepam after i.m. injection. The systemic exposure to clonazepam was not affected by the route of extravascular administration. Statistical evaluation of these kinetic data showed differences in the absorption rate, so that clonazepam given by the i.m. route is not bioequivalent to the oral route. On the basis of the results of this study, we would recommend the same i.m. and p.o. dose in epileptic patients

  8. Oral administration of myostatin-specific recombinant Saccharomyces cerevisiae vaccine in rabbit.

    PubMed

    Liu, Zhongtian; Zhou, Gang; Ren, Chonghua; Xu, Kun; Yan, Qiang; Li, Xinyi; Zhang, Tingting; Zhang, Zhiying

    2016-04-29

    Yeast is considered as a simple and cost-effective host for protein expression, and our previous studies have proved that Saccharomyces cerevisiae can deliver recombinant protein and DNA into mouse dendritic cells and can further induce immune responses as novel vaccines. In order to know whether similar immune responses can be induced in rabbit by oral administration of such recombinant S. cerevisiae vaccine, we orally fed the rabbits with heat-inactivated myostatin-recombinant S. cerevisiae for 5 weeks, and then myostatin-specific antibody in serum was detected successfully by western blotting and ELISA assay. The rabbits treated with myostatin-recombinant S. cerevisiae vaccine grew faster and their muscles were much heavier than that of the control group. As a common experimental animal and a meat livestock with great economic value, rabbit was proved to be the second animal species that have been successfully orally immunized by recombinant S. cerevisiae vaccine after mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Influence of Particle Geometry on Gastrointestinal Transit and Absorption following Oral Administration.

    PubMed

    Li, Dong; Zhuang, Jie; He, Haisheng; Jiang, Sifan; Banerjee, Amrita; Lu, Yi; Wu, Wei; Mitragotri, Samir; Gan, Li; Qi, Jianping

    2017-12-13

    Geometry has been considered as one of the important parameters in nanoparticle design because it affects cellular uptake, transport across the physiological barriers, and in vivo distribution. However, only a few studies have been conducted to elucidate the influence of nanoparticle geometry in their in vivo fate after oral administration. This article discloses the effect of nanoparticle shape on transport and absorption in gastrointestinal (GI) tract. Nanorods and nanospheres were prepared and labeled using fluorescence resonance energy transfer molecules to track the in vivo fate of intact nanoparticles accurately. Results demonstrated that nanorods had significantly longer retention time in GI tract compared with nanospheres. Furthermore, nanorods exhibited stronger ability of penetration into space of villi than nanospheres, which is the main reason of longer retention time. In addition, mesenteric lymph transported 1.75% nanorods within 10 h, which was more than that with nanospheres (0.98%). Fluorescent signals arising from nanoparticles were found in the kidney but not in the liver, lung, spleen, or blood, which could be ascribed to low absorption of intact nanoparticles. In conclusion, nanoparticle geometry influences in vivo fate after oral delivery and nanorods should be further investigated for designing oral delivery systems for therapeutic drugs, vaccines, or diagnostic materials.

  10. Dissolution and bioavailability enhancement of alpha-asarone by solid dispersions via oral administration.

    PubMed

    Deng, Li; Wang, Yu; Gong, Tao; Sun, Xun; Zhang, Zhi-Rong

    2017-11-01

    Alpha (α)-asarone (1-propenyl-2,4,5-methoxybenzol) (ARE) has been extensively used to treat chronic obstructive pulmonary diseases (COPD), bronchial asthma, pneumonia, and epilepsy. Due to its poor solubility and bioavailability, ARE was clinically administered via intravenous injection. However, severe allergies were often reported due to the presence of solublizers in the injection formulation. In our study, we sought to explore the biopharmaceutical classification of ARE, elucidate the mechanisms behind ARE absorption, and to develop a viable formulation to improve the oral bioavailability of ARE. ARE was not a P-glycoprotein substrate, which was absorbed in the passive mode without site specificity in the gastrointestinal tract. Solid dispersions prepared using hydrophilic matrix materials such as Pluronic F68, and polyethylene glycol (PEG) of varying molecular weights (PEG4K, PEG10K, and PEG20K) were proven to significantly improve the dissolution of ARE in vitro and the oral bioavailability of ARE in rats, which represent a promising strategy for the oral administration of ARE and other BCS II compounds.

  11. Pharmacokinetics of opicapone, a third-generation COMT inhibitor, after single and multiple oral administration: A comparative study in the rat

    SciTech Connect

    Gonçalves, Daniela

    Opicapone is a novel potent, reversible and purely peripheral catechol-O-methyltransferase inhibitor that has been developed to be used as an adjunct to levodopa/aromatic L-amino acid decarboxylase inhibitor therapy for Parkinson's disease. Thus, this study aimed to compare the plasma pharmacokinetics of opicapone and its active metabolite (BIA 9-1079) after the administration of single and multiple oral doses to rats. Wistar rats (n = 8 per group) were orally treated with single (30, 60 or 90 mg/kg) or multiple (30 mg/kg once-daily for seven consecutive days) oral doses of opicapone. Blood samples were collected up to 24 h post-dosing through amore » cannula introduced in the tail vein of rats. After quantifying opicapone and BIA 9-1079 in plasma, a non-compartmental pharmacokinetic analysis was performed. Opicapone was quickly absorbed (time to reach the maximum plasma concentration ≤ 2 h) in both dosage regimens and the extent of systemic exposure to opicapone increased approximately in a dose-proportional manner after single-dosing within the studied dose range (30–90 mg/kg). Opicapone and BIA 9-1079 showed a relatively short plasma elimination half-life (1.58–4.50 h) and a small systemic accumulation after multiple-dosing. Hence, no pharmacokinetic concerns are expected when opicapone is administered with a once-daily dosing regimen. - Highlights: • Opicapone is relatively rapid absorbed after oral administration to rats. • Systemic exposure to opicapone increases approximately in a dose-proportional manner. • Opicapone and BIA 9-1079 show a small systemic accumulation after multiple-dosing.« less

  12. The impact of the mode of survey administration on estimates of daily smoking for mobile phone only users.

    PubMed

    Hanna, Joseph; Cordery, Damien V; Steel, David G; Davis, Walter; Harrold, Timothy C

    2017-04-20

    Over the past decade, there have been substantial changes in landline and mobile phone ownership, with a substantial increase in the proportion of mobile-only households. Estimates of daily smoking rates for the mobile phone only (MPO) population have been found to be substantially higher than the rest of the population and telephone surveys that use a dual sampling frame (landline and mobile phones) are now considered best practice. Smoking is seen as an undesirable behaviour; measuring such behaviours using an interviewer may lead to lower estimates when using telephone based surveys compared to self-administered approaches. This study aims to assess whether higher daily smoking estimates observed for the mobile phone only population can be explained by administrative features of surveys, after accounting for differences in the phone ownership population groups. Data on New South Wales (NSW) residents aged 18 years or older from the NSW Population Health Survey (PHS), a telephone survey, and the National Drug Strategy Household Survey (NDSHS), a self-administered survey, were combined, with weights adjusted to match the 2013 population. Design-adjusted prevalence estimates and odds ratios were calculated using survey analysis procedures available in SAS 9.4. Both the PHS and NDSHS gave the same estimates for daily smoking (12%) and similar estimates for MPO users (20% and 18% respectively). Pooled data showed that daily smoking was 19% for MPO users, compared to 10% for dual phone owners, and 12% for landline phone only users. Prevalence estimates for MPO users across both surveys were consistently higher than other phone ownership groups. Differences in estimates for the MPO population compared to other phone ownership groups persisted even after adjustment for the mode of collection and demographic factors. Daily smoking rates were consistently higher for the mobile phone only population and this was not driven by the mode of survey collection. This supports

  13. Oral administration of the antioxidant, N-acetylcysteine, abrogates diabetes-induced endothelial dysfunction.

    PubMed

    Pieper, G M; Siebeneich, W

    1998-07-01

    Oxidative stress is believed to play an important role in the development of vascular complications associated with diabetes mellitus. In this study, we examined the efficacy of long-term treatment with the antioxidant, N-acetylcysteine, in preventing the development of defective endothelium-dependent relaxation in streptozotocin-induced, Sprague-Dawley diabetic rats. At 48 h after injection of streptozotocin, a portion of diabetic rats received 250 mg/L N-acetylcysteine in drinking water for a total duration of 8 weeks. Oral administration did not alter the increase in blood glucose or the reduction in serum insulin but did modestly reduce total glycosylated hemoglobin. In precontracted thoracic aortic rings suspended in isolated tissue baths, endothelium-dependent relaxation to acetylcholine was impaired in diabetic rings compared with control rings. Endothelium-independent relaxation to nitroglycerin was unaltered. Long-term oral administration of N-acetylcysteine did not alter responses to nitroglycerin but completely prevented the defective relaxation to acetylcholine. These studies indicate a dissociation between glycemic control and correction of endothelial dysfunction and suggest that long-term exposure to reactive oxygen subsequent to diabetes rather than hyperglycemia per se is responsible for the development of endothelial dysfunction in diabetes mellitus.

  14. A safety study of oral tangeretin and xanthohumol administration to laboratory mice.

    PubMed

    Vanhoecke, Barbara W; Delporte, Femke; Van Braeckel, Eva; Heyerick, Arne; Depypere, Herman T; Nuytinck, Margareta; De Keukeleire, Denis; Bracke, Marc E

    2005-01-01

    The detection of molecular targets for flavonoids in cell signalling has opened new perspectives for their application in medicine. Both tangeretin, a citrus methoxyflavone, and xanthohumol, the main prenylated chalcone present in hops (Humulus lupulus L.), act on the mitogen-activated protein kinase pathway and await further investigation for administration in vivo. A safety study was designed in laboratory mice orally administered concentrates of purified tangeretin (1 x 10(-4) M) or xanthohumol (5 x 10(-4) M) at libitum for 4 weeks. Blood samples were collected for the analysis of a variety of haematological and biochemical parameters. A reduction of the circulating lymphocyte number was noticed for tangeretin, while all other parameters were unaffected by treatment with either tangeretin or xanthohumol. The parameters encompassed an integrity check of the following tissues and organs: bone marrow, liver, exocrine pancreas, kidneys, muscles, thyroid, ovaries and surrenal cortex. Furthermore, no differences were noted in the metabolism of proteins, lipids, carbohydrates and uric acid, as well as in ion concentrations. All data indicate that oral administration of tangeretin or xanthohumol to laboratory mice does not affect major organ functions and opens the gate for further safety studies in humans.

  15. Oral Administration of Probiotics Increases Paneth Cells and Intestinal Antimicrobial Activity.

    PubMed

    Cazorla, Silvia I; Maldonado-Galdeano, Carolina; Weill, Ricardo; De Paula, Juan; Perdigón, Gabriela D V

    2018-01-01

    The huge amount of intestinal bacteria represents a continuing threat to the intestinal barrier. To meet this challenge, gut epithelial cells produce antimicrobial peptides (AMP) that act at the forefront of innate immunity. We explore whether this antimicrobial activity and Paneth cells, the main intestinal cell responsible of AMP production, are influenced by probiotics administration, to avoid the imbalance of intestinal microbiota and preserve intestinal barrier. Administration of Lactobacillus casei CRL 431 (Lc 431) and L. paracasei CNCM I-1518 (Lp 1518) to 42 days old mice, increases the number of Paneth cells on small intestine, and the antimicrobial activity against the pathogens Staphylococcus aureus and Salmonella Typhimurium in the intestinal fluids. Specifically, strong damage of the bacterial cell with leakage of cytoplasmic content, and cellular fragmentation were observed in S. Typhimurium and S. aureus . Even more important, probiotics increase the antimicrobial activity of the intestinal fluids at the different ages, from weaning (21 days old) to old age (180 days old). Intestinal antimicrobial activity stimulated by oral probiotics, do not influence significantly the composition of total anaerobic bacteria, lactobacilli and enterobacteria in the large intestine, at any age analyzed. This result, together with the antimicrobial activity observed against the same probiotic bacteria; endorse the regular consumption of probiotics without adverse effect on the intestinal homeostasis in healthy individuals. We demonstrate that oral probiotics increase intestinal antimicrobial activity and Paneth cells in order to strengthen epithelial barrier against pathogens. This effect would be another important mechanism by which probiotics protect the host mainly against infectious diseases.

  16. Toxicokinetics of short-chain chlorinated paraffins in Sprague-Dawley rats following single oral administration.

    PubMed

    Geng, Ningbo; Zhang, Haijun; Xing, Liguo; Gao, Yuan; Zhang, Baoqin; Wang, Feidi; Ren, Xiaoqian; Chen, Jiping

    2016-02-01

    Short-chain chlorinated paraffins (SCCPs) have attracted considerable attention for their characteristic of persistent organic pollutants. However, very limited information is available for their toxicokinetic characteristics, limiting the evaluation of their health risks. In this study, we performed a toxicokinetics study to explore the absorption and excretion processes of SCCPs (a mixture of C10-, C11-, C12- and C13-CPs) after a single oral administration to the Sprague-Dawley rats. The toxicokinetic results showed that peak blood concentration of total SCCPs was attained at 2.8 day with Cmax value of 2.3 mg L(-1). The half-lives of total SCCPs in blood for the absorption t1/2 (ka), distribution t1/2 (α) and elimination phases t1/2 (β) were calculated to be 1.0, 1.7 and 6.6 days, respectively. During the 28 days post-dosing, about 27.9% and 3.5% of orally administrated SCCPs were excreted through feces and urine without metabolism, respectively. Congener group abundance profiles indicate a relative increase of Cl5-SCCPs in blood and urine in the elimination stage, and a higher accumulation of Cl8-10-SCCPs in feces. The distribution discrepancies of SCCPs congener groups in blood and excreta were more dependent on chlorine contents than on carbon chain lengths. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Pharmacokinetic Study of 7 Compounds Following Oral Administration of Fructus Aurantii to Depressive Rats

    PubMed Central

    Zhang, Xianhua; Han, Linran; Liu, Jin; Xu, Qiuyue; Guo, Yuxin; Zheng, Wan; Wang, Jian; Huang, Xi; Ren, Ping

    2018-01-01

    In the present study, the pharmacokinetics of multi-components (naringenin, nobiletin, meranzin hydrate, narirutin, naringin, hesperidin, and neohesperidin) were investigated in acute depressive rats following oral administration of Fructus Aurantii (Zhi-Qiao, ZQ) extract (20 g/kg). A rapid and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established to quantitatively or qualitatively analyze the 7 absorbed ingredients in the plasma, hippocampus and cortex of acute depressive rats. Biological samples were separated on a 300SB-C18 column, and the 7 compounds were detected with sequential positive and negative ionization modes. Our results confirmed that ZQ has antidepressant effects by decreasing the immobility time. In addition, this validated method showed good linearity (r ≥ 0.9987), and the lower limits of quantification were 2.73–16.38 ng/mL for the 7 analytes. This method successfully determined the pharmacokinetics of the 7 compounds and separated two pairs of isomers in plasma of acute depressive rats following oral administration of ZQ extracts. The 7 active ingredients were also identified as marked compounds in target tissues and should be further examined in pharmacokinetic studies with acute depressive rats. So, pharmacokinetic compounds were precisely linked with the antidepressant effect of ZQ in our study. This relationship is well-understood and contributes to the application of Traditional Chinese Medicine (TCM). PMID:29556193

  18. Oral administration of antioxidants improves skin wound healing in diabetic mice.

    PubMed

    Pessoa, Ana Flávia Marçal; Florim, Juliana Costa; Rodrigues, Hosana Gomes; Andrade-Oliveira, Vinicius; Teixeira, Simone A; Vitzel, Kaio Fernando; Curi, Rui; Saraiva Câmara, Niels Olsen; Muscará, Marcelo N; Lamers, Marcelo Lazzaron; Santos, Marinilce Fagundes

    2016-11-01

    Oxidative stress aggravates several long-term complications in diabetes mellitus. We evaluated the effectiveness of the oral administration of antioxidants (vitamins E and C, 40 and 100 mg/kg b.w., respectively) on skin wound healing acceleration in alloxan-induced diabetic mice. Mice were wounded 30 days after the induction of diabetes. Antioxidants were effective in preventing oxidative stress, as assessed by TBARS. The enzymes catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase were increased in diabetics on the 3rd day post-wounding; catalase and glutathione peroxidase remained still augmented in diabetics after 14th day postwounding, and the treatment with vitamins restored their activities to control. After 3 days, diabetic mice showed lower infiltration of inflammatory cells (including CD11b + and Ly6G + cells) and reduced levels of KC, TNF-α, IL-1β, and IL-12 p40 when compared with control mice. The treatment restored cytokine levels. After 14 days, diabetic mice showed late wound closure, persistent inflammation and delayed reepithelialization, accompanied by an increase in MIG + /CD206 - macrophages whereas CD206 + /MIG - macrophages were decreased. Cytokines IL-12p40, TNF-α, IL-1β, and KC were increased and normal levels were restored after treatment with antioxidants. These results suggest that oxidative stress plays a major role in diabetic wound healing impairment and the oral administration of antioxidants improves healing by modulating inflammation and the antioxidant system with no effect on glycemia. © 2016 by the Wound Healing Society.

  19. Pharmacokinetics of opicapone, a third-generation COMT inhibitor, after single and multiple oral administration: A comparative study in the rat.

    PubMed

    Gonçalves, Daniela; Alves, Gilberto; Fortuna, Ana; Soares-da-Silva, Patrício; Falcão, Amílcar

    2017-05-15

    Opicapone is a novel potent, reversible and purely peripheral catechol-O-methyltransferase inhibitor that has been developed to be used as an adjunct to levodopa/aromatic L-amino acid decarboxylase inhibitor therapy for Parkinson's disease. Thus, this study aimed to compare the plasma pharmacokinetics of opicapone and its active metabolite (BIA 9-1079) after the administration of single and multiple oral doses to rats. Wistar rats (n=8 per group) were orally treated with single (30, 60 or 90mg/kg) or multiple (30mg/kg once-daily for seven consecutive days) oral doses of opicapone. Blood samples were collected up to 24h post-dosing through a cannula introduced in the tail vein of rats. After quantifying opicapone and BIA 9-1079 in plasma, a non-compartmental pharmacokinetic analysis was performed. Opicapone was quickly absorbed (time to reach the maximum plasma concentration≤2h) in both dosage regimens and the extent of systemic exposure to opicapone increased approximately in a dose-proportional manner after single-dosing within the studied dose range (30-90mg/kg). Opicapone and BIA 9-1079 showed a relatively short plasma elimination half-life (1.58-4.50h) and a small systemic accumulation after multiple-dosing. Hence, no pharmacokinetic concerns are expected when opicapone is administered with a once-daily dosing regimen. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Effect of intermittent oral administration of ponazuril on experimental Sarcocystis neurona infection of horses.

    PubMed

    Mackay, Robert J; Tanhauser, Susan T; Gillis, Karen D; Mayhew, Ian G; Kennedy, Tom J

    2008-03-01

    To evaluate the effect of intermittent oral administration of ponazuril on immunoconversion against Sarcocystis neurona in horses inoculated intragastrically with S neurona sporocysts. 20 healthy horses that were seronegative for S neurona-specific IgG. 5 control horses were neither inoculated with sporocysts nor treated. Other horses (5 horses/group) each received 612,500 S neurona sporocysts via nasogastric tube (day 0) and were not treated or were administered ponazuril (20 mg/kg, PO) every 7 days (beginning on day 5) or every 14 days (beginning on day 12) for 12 weeks. Blood and CSF samples were collected on day - 1 and then every 14 days after challenge for western blot assessment of immunoconversion. Clinical signs of equine protozoal myeloencephalitis (EPM) were monitored, and tissues were examined histologically after euthanasia. Sera from all challenged horses yielded positive western blot results within 56 days. Immunoconversion in CSF was detected in only 2 of 5 horses that were treated weekly; all other challenged horses immunoconverted within 84 days. Weekly administration of ponazuril significantly reduced the antibody response against the S neurona 17-kd antigen in CSF. Neurologic signs consistent with EPM did not develop in any group; likewise, histologic examination of CNS tissue did not reveal protozoa or consistent degenerative or inflammatory changes. Administration of ponazuril every 7 days, but not every 14 days, significantly decreased intrathecal anti-S neurona antibody responses in horses inoculated with S neurona sporocysts. Protocols involving intermittent administration of ponazuril may have application in prevention of EPM.

  1. Pharmacokinetics of tramadol following intravenous and oral administration in male rhesus macaques (Macaca mulatta)

    PubMed Central

    Kelly, Kristi R.; Pypendop, Bruno H.; Christe, Kari L.

    2014-01-01

    Recently, tramadol and its active metabolite, O-desmethyltramadol (M1), have been studied as analgesic agents in various traditional veterinary species (e.g. dogs, cats, etc.). This study explores the pharmacokinetics of tramadol and M1 after intravenous (IV) and oral (PO) administration in rhesus macaques (Macaca mulatta), a nontraditional veterinary species. Rhesus macaques are Old World monkeys that are commonly used in biomedical research. Effects of tramadol administration to monkeys are unknown, and research veterinarians may avoid inclusion of this drug into pain management programs due to this limited knowledge. Four healthy, socially-housed, adult male rhesus macaques (Macaca mulatta) were used in this study. Blood samples were collected prior to, and up to 10 h post tramadol administration. Serum tramadol and M1 were analyzed using liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic analysis was performed. Tramadol clearance was 24.5 (23.4-32.7) mL/min/kg. Terminal half-life of tramadol was 111 (106-127) min IV and 133 (84.9-198) min PO. Bioavailability of tramadol was poor [3.47% (2.14-5.96%)]. Maximum serum concentration of M1 was 2.28 (1.88-2.73) ng/mL IV and 11.2 (9.37-14.9) ng/mL PO. Sedation and pruritus were observed after IV administration (180 words). PMID:25488714

  2. Pharmacokinetics of enrofloxacin after oral, intramuscular and bath administration in crucian carp (Carassius auratus gibelio).

    PubMed

    Shan, Q; Fan, J; Wang, J; Zhu, X; Yin, Y; Zheng, G

    2018-02-01

    The pharmacokinetics of enrofloxacin (ENR) was studied in crucian carp (Carassius auratus gibelio) after single administration by intramuscular (IM) injection and oral gavage (PO) at a dose of 10 mg/kg body weight and by 5 mg/L bath for 5 hr at 25°C. The plasma concentrations of ENR and ciprofloxacin (CIP) were determined by HPLC. Pharmacokinetic parameters were calculated based on mean ENR or CIP concentrations using WinNonlin 6.1 software. After IM, PO and bath administration, the maximum plasma concentration (C max ) of 2.29, 3.24 and 0.36 μg/ml was obtained at 4.08, 0.68 and 0 hr, respectively; the elimination half-life (T 1/2β ) was 80.95, 62.17 and 61.15 hr, respectively; the area under the concentration-time curve (AUC) values were 223.46, 162.72 and 14.91 μg hr/ml, respectively. CIP, an active metabolite of enrofloxacin, was detected and measured after all methods of drug administration except bath. It is possible and practical to obtain therapeutic blood concentrations of enrofloxacin in the crucian carp using IM, PO and bath immersion administration. © 2017 John Wiley & Sons Ltd.

  3. 20 CFR 416.1448 - Deciding a case without an oral hearing before an administrative law judge.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Deciding a case without an oral hearing before an administrative law judge. 416.1448 Section 416.1448 Employees' Benefits SOCIAL SECURITY... Review Process, and Reopening of Determinations and Decisions Administrative Law Judge Hearing Procedures...

  4. 20 CFR 404.948 - Deciding a case without an oral hearing before an administrative law judge.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Deciding a case without an oral hearing before an administrative law judge. 404.948 Section 404.948 Employees' Benefits SOCIAL SECURITY... Process, and Reopening of Determinations and Decisions Administrative Law Judge Hearing Procedures § 404...

  5. Oral administration of analgesia and anxiolysis for pain associated with bone marrow biopsy.

    PubMed

    Talamo, Giampaolo; Liao, Jason; Bayerl, Michael G; Claxton, David F; Zangari, Maurizio

    2010-03-01

    Medical literature provides only scarce data about the degree of pain experienced by patients undergoing a bone marrow aspiration and biopsy (BMAB), and little is known about the factors that can modify the perception of pain. In this study, we evaluated the effectiveness of a combination of analgesia and anxiolysis in reducing the pain score of patients undergoing BMAB. Eighty-four consecutive adult patients underwent BMAB after local anesthesia with 5 mL of lidocaine hydrochloride 1% aqueous solution in the left posterior superior iliac crest. Analgesia was obtained with acetaminophen 650 mg and oxycodone 10 mg, and anxiolysis was obtained with lorazepam 2 mg, all drugs given once orally 30 min before the procedure. We assessed the pain level with the Wong-Baker Faces Pain Rating Scale, which distinguishes six levels of pain, from 0 to 5. The 34 patients who received an oral administration of analgesia and anxiolysis reported pain at lower levels, i.e., in the range of 0-2, more frequently than the 50 patients who underwent BMAB without analgesia/anxiolysis (78% vs 64%, respectively). Among several predictors analyzed using a multivariate regression model, three were found to be associated with decreased pain level: the use of analgesia/anxiolysis, male sex, and increase in age (all with p values <0.05). Length of the extracted bone specimen, body mass index, and need of a spinal needle for anesthesia in obese patients did not predict for pain level. An oral administration of prophylactic regimen of analgesia and anxiolysis, at the above-mentioned doses, produced a statistically significant reduction of the perception of pain in patients undergoing BMAB, but its effect did not seem to provide a major and clinically significant reduction of pain level.

  6. Oral L-glutamine administration attenuated cutaneous wound healing in Wistar rats.

    PubMed

    Goswami, Saurabh; Kandhare, Amit; Zanwar, Anand A; Hegde, Mahabaleshwar V; Bodhankar, Subhash L; Shinde, Sudhir; Deshmukh, Shahaji; Kharat, Ravindran

    2016-02-01

    The objective of this study was to evaluate the wound healing potential of L-glutamine in laboratory rats using excision and incision wound models. Excision wounds of size 500 mm(2) and depth 2 mm were made on the dorsal portion of male Wistar rats (230-250 g) and were used for the study of oral L-glutamine (1 g/kg) treatment on the rate of contraction of wound and epithelisation. Histological evaluation of wound tissue was also performed. Six-centimetre-long two linear-paravertebral incisions in male Wistar rats (230-250 g) were used to study the effect of L-glutamine (1 g/kg, p.o.) treatment on tensile strength, total protein and hydroxyproline content in the incision model. Oral administration of L-glutamine (1 g/kg) significantly decreased wound area, epithelisation period and wound index, whereas the rate of wound contraction significantly increased (P < 0·001) when compared with vehicle control rats in the excision wound model. Tensile strength, hydroxyproline content and protein level were significantly increased (P < 0·001) in L-glutamine (1 g/kg, p.o.)-treated rats when compared with vehicle control rats in the incision wound model. Histological evaluation of wound tissue from L-glutamine (1 g/kg, p.o.)-treated rats showed complete epithelialisation with new blood vessel formation and high fibrous tissues in the excision wound model. In conclusion, oral administration of l-glutamine (1 g/kg) promotes wound healing by acting on various stages of wound healing such as collagen synthesis, wound contraction and epithelialisation. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  7. Efficacy of Meglumine Antimoniate under Low Polymerization State Orally Administrated in Murine Model of Visceral Leishmaniasis.

    PubMed

    Kato, Kelly C; de Morais-Teixeira, Eliane; Islam, Arshad; Leite, M Fatima; Demicheli, Cynthia; de Castro, Whocely V; Corrêa-Junior, José D; Rabello, Ana; Frézard, Frédéric

    2018-06-04

    Progress towards the improvement of meglumine antimoniate (MA) commercially known as Glucantime®, a highly effective but also toxic antileishmanial drug, has been hindered by the lack of knowledge and control on its chemical composition. Here, MA was manipulated chemically with the aim of achieving an orally effective drug. MA compounds were synthesized from either antimony pentachloride (MA-SbCl 5 ) or potassium hexahydroxyantimonate (MA-KSb(OH) 6 ) and prepared under low polymerization state. Those were compared to Glucantime® regarding chemical composition, permeation properties across cellulose membrane and Caco-2 cell monolayer and uptake by peritoneal macrophages. MA-SbCl 5 and MA-KSb(OH) 6 were characterized as less polymerized and more permeable 2:2 Sb-meglumine complexes, when compared to Glucantime® that consisted in a mixture of 2:3 and 3:3 Sb-meglumine complexes. The antileishmanial activity and hepatic uptake of all compounds were evaluated after oral administration in BALB/c mice infected with Leishmania infantum chagasi , as model of visceral leishmaniasis (VL). The synthetic MA compounds given at 300 mg Sb/kg/12h for 30 days reduced significantly spleen and liver parasite burdens, in contrast to Glucantime® at the same dose. The greater activity of synthetic compounds could be attributed to their higher intestinal absorption and accumulation efficiency in the liver. MA-SbCl 5 given orally was as efficacious as Glucantime® by parenteral route (80 mg Sb/kg/24h IP). This data taken altogether suggests that treatment with less polymerized form of MA by oral route may be effective for the treatment of VL. Copyright © 2018 American Society for Microbiology.

  8. Oral administration of amphotericin B nanoparticles: antifungal activity, bioavailability and toxicity in rats.

    PubMed

    Radwan, Mahasen A; AlQuadeib, Bushra T; Šiller, Lidija; Wright, Matthew C; Horrocks, Benjamin

    2017-11-01

    Amphotericin B (AMB) is used most commonly in severe systemic life-threatening fungal infections. There is currently an unmet need for an efficacious (AMB) formulation amenable to oral administration with better bioavailability and lower nephrotoxicity. Novel PEGylated polylactic-polyglycolic acid copolymer (PLGA-PEG) nanoparticles (NPs) formulations of AMB were therefore studied for their ability to kill Candida albicans (C. albicans). The antifungal activity of AMB formulations was assessed in C. albicans. Its bioavalability was investigated in nine groups of rats (n = 6). Toxicity was examined by an in vitro blood hemolysis assay, and in vivo nephrotoxicity after single and multiple dosing for a week by blood urea nitrogen (BUN) and plasma creatinine (PCr) measurements. The MIC of AMB loaded to PLGA-PEG NPs against C. albicans was reduced two to threefold compared with free AMB. Novel oral AMB delivery loaded to PLGA-PEG NPs was markedly systemically available compared to Fungizone® in rats. The addition of 2% of GA to the AMB formulation significantly (p < 0.05) improved the bioavailability from 1.5 to 10.5% and the relative bioavailability was > 790% that of Fungizone®. The novel AMB formulations showed minimal toxicity and better efficacy compared to Fungizone®. No nephrotoxicity in rats was detected after a week of multiple dosing of AMB NPs based on BUN and PCr, which remained at normal levels. An oral delivery system of AMB-loaded to PLGA-PEG NPs with better efficacy and minimal toxicity was formulated. The addition of glycyrrhizic acid (GA) to AMB NPs formulation resulted in a significant oral absorption and improved bioavailability in rats.

  9. Systemic antibiotic prophylaxis prior to gastrointestinal surgery - is oral administration of doxycycline and metronidazole adequate?

    PubMed

    Giske, Anneli; Nymo, Linn Såve; Fuskevåg, Ole-Martin; Amundsen, Siri; Simonsen, Gunnar Skov; Lassen, Kristoffer

    Antibiotic prophylaxis is recommended prior to a wide range of gastrointestinal operations to reduce the rate of surgical site infections (SSIs). Traditional intravenous (IV) drugs are costly and their preparation strains nursing resources at the wards. While oral administration may attenuate these limitations, its use remains limited. We aimed to assess whether a dual oral antibiotic prophylaxis regimen provides adequate serum concentrations throughout the surgical procedure. We measured serum concentrations of doxycycline and metronidazole following single oral doses of 400 mg doxycycline and 1200 mg metronidazole at first incision and repeated at wound closure in a cohort of patients undergoing elective gastrointestinal surgery. Both drugs were dispensed at least two hours before skin incision. Serum concentrations were compared to minimum inhibitory concentrations (MIC) and epidemiological cut-off values (ECOFFs) for relevant pathogens. Mean serum concentrations of doxycycline at first incision and at wound closure were 5.75 mg/L and 4.66 mg/L and of metronidazole 18.88 mg/L and 15.56 mg/L, respectively. Metronidazole concentrations were above ECOFF (2 mg/L) for relevant anaerobic species in 103/104 of patients in both samples. Doxycycline serum concentrations were above the ECOFF for common Enterobacteriaceae species (4 mg/L) in both samples in 58/104 patients (55.8%). A single dose of orally administered metronidazole provides adequate concentrations throughout surgery in a heterogeneous cohort of patients. Uncertainty persists regarding the adequacy of doxycycline concentrations, as the optimal serum level of doxycycline in a prophylactic setting has not been established.

  10. A conscious rat model involving bradycardia and hypotension after oral administration: a toxicokinetical study of aconitine.

    PubMed

    Zhang, Panpan; Kong, Dezhi; Du, Qian; Zhao, Jing; Li, Qing; Zhang, Jianghua; Li, Tonghui; Ren, Leiming

    2017-06-01

    1. A model of aconitine-induced bradycardia and hypotension, which is similar to aconitine poisoning in humans, was constructed in conscious rats by oral administration. 2. Blood pressure (BP) and heart rate (HR) of Sprague-Dawley rats were measured using a volume pressure recording (VPR) system. The pharmacokinetics of toxic doses of aconitine and its metabolites were analyzed using UPLC-MS/MS. 3. The HR was significantly decreased by 29% at 2 h after oral administration of 200 μg/kg aconitine. When the dose was increased to 400 μg/kg, systolic BP and diastolic BP were significantly decreased by 11% and 12% at 2 h after the administration, except when bradycardia occurred at 2 h and 4 h. The drug concentration-time curve showed a double-peak phenomenon in rats administered a 400 μg/kg dose. The AUC 0-12 h value in the 400 μg/kg group significantly increased 0.8-fold compared to the 200 μg/kg group. Moreover, a high plasma concentration of 16-O-demethyaconitine was found in the rats that received two toxic doses. 4. In conclusion, bradycardia and hypotension are induced in conscious rats by a toxic dose of aconitine (400 μg/kg), and there was no significant difference in dose-normalized AUC 0-12 h values between oral administrations of 200 μg/kg and that of 400 μg/kg. However, the dose-normalized C max and AUC 0-12 h values in 200 μg/kg and 400 μg/kg groups were significantly smaller than those in 100 μg/kg group. The metabolites of aconitine, 16-O-demethyaconitine, and benzoylaconitine may also contribute to the hypotensive response.

  11. [Effect of oral administration of ascorbic acid on insulin sensitivity and lipid profile in obese individuals].

    PubMed

    Martínez-Abundis, E; Pascoe-González, S; González-Ortiz, M; Mora-Martínez, J M; Cabrera-Pivaral, C E

    2001-01-01

    The aim of this study was to identify the effect of an oral ascorbic acid (AA) supplement on lipid profile and insulin sensitivity in obese people. A randomized double-blind clinical trial placebo controlled was performed in 16 obese male volunteers [body mass index (BMI) 30-40 kg/m2]. Eight received orally 1 g of AA daily for four weeks and the other eight volunteers received placebo by the same scheme and period of time. Before and after the pharmacological intervention were measured total cholesterol, high-density-lipoprotein (HDL) cholesterol, triglycerides, glucose, creatinine and uric acid. Low-density-lipoprotein (LDL) cholesterol and very-low-density-lipoprotein (VLDL) triglycerides were calculated using formulas. In order to assess insulin sensitivity before and after the intervention, the steady-state glucose (SSG) was calculated from the insulin suppression test modified with octreotide. There were not significant differences in clinical characteristics between both groups. Basal metabolic profile and SSG were similar between both groups. There were not significant differences in both groups between before and after the intervention in metabolic profile and insulin sensitivity. AA did not modify the lipid profile nor insulin sensitivity in the group of obese people studied.

  12. Pharmacokinetics of dextromethorphan and its metabolites in horses following a single oral administration.

    PubMed

    Corado, Carley R; McKemie, Daniel S; Knych, Heather K

    2017-06-01

    Dextromethorphan is an N-methyl-D-aspartate (NMDA) non-competitive antagonist commonly used in human medicine as an antitussive. Dextromethorphan is metabolized in humans by cytochrome P450 2D6 into dextrorphan, which is reported to be more potent than the parent compound. The goal of this study is to describe the metabolism of and determine the pharmacokinetics of dextromethorphan and its major metabolites following oral administration to horses. A total of 23 horses received a single oral dose of 2 mg/kg. Blood samples were collected at time 0 and at various times up to 96 h post drug administration. Urine samples were collected from 12 horses up to 120 h post administration. Plasma and urine samples were analyzed using liquid chromatography-mass spectrometry, and the resulting data analyzed using non-compartmental analysis. The C max , T max , and the t 1/2 of dextromethorphan were 519.4 ng/mL, 0.55 h, and 12.4 h respectively. The area under the curve of dextromethorphan, free dextrorphan, and conjugated dextrorphan were 563.8, 2.19, and 6,691 h*ng/mL respectively. In addition to free and glucuronidated dextrorphan, several additional glucuronide metabolites were identified in plasma, including hydroxyl-desmethyl dextrorphan, desmethyl dextrorphan, and three forms of hydroxylated dextrorphan. Dextromethorphan was found to be eliminated from the urine predominately as the O-demethylated metabolite, dextrorphan. Several additional metabolites including several novel hydroxy-dextrorphan metabolites were also detected in the urine in both free and glucuronidated forms. No significant undesirable behavioural effects were noted throughout the duration of the study. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  13. Oral Fluid Cocaine and Benzoylecgonine Concentrations Following Controlled Intravenous Cocaine Administration

    PubMed Central

    Ellefsen, Kayla N.; Concheiro, Marta; Pirard, Sandrine; Gorelick, David A.; Huestis, Marilyn A.

    2016-01-01

    Limited oral fluid (OF) pharmacokinetic data collected with commercially available collection devices after controlled cocaine administration hinder OF result interpretations. Ten cocaine-using adults provided OF, collected with Oral-Eze® (OE) and StatSure Saliva Sampler™ (SS) devices, an hour prior to and up to 69 h after 25 mg intravenous (IV) cocaine administration. Cocaine and benzoylecgonine (BE) were quantified by a validated 2D-GC-MS method. Large inter-subject variability was observed. Cocaine was detected in OF in the first 0.17 h sample after IV administration, with much more rapid elimination than BE. OE median observed Cmax (range) was 932 (394–1,574) μg/L for cocaine and 248 (96.9–953) μg/L for BE. SS median (range) observed cocaine and BE Cmax trended lower at 732 (83.3–1,892) μg/L and 360 (77.2–836) μg/L, respectively. OE and SS cocaine OF detection times were 12.5 and 6.5 h and for BE 30.5 and 28.0 h, respectively at 1 μg/L. There were no significant pharmacokinetic differences between OE and SS OF collection devices, except cocaine half-life was significantly shorter in SS OF specimens. This difference could be attributed to differences in stabilizing buffers present in OF collection devices, which may affect cocaine stability in OF specimens, or decreased recovery from collection pads. Both OE and SS OF collection devices were effective in monitoring cocaine and metabolite concentrations with similar detection windows. Furthermore, we demonstrated that different confirmatory OF cutoffs can be selected to produce shorter or longer cocaine and metabolite detection windows to address specific needs of clinical and forensic drug testing programs. PMID:26851651

  14. Classrooms and Curriculum Come Alive with Music: A Sequential Approach of Teaching Music to Elementary Students Using Daily Oral Music Lessons.

    ERIC Educational Resources Information Center

    Sharp, Lanette

    Developed specifically for classroom teachers with a limited background in music, oral music lessons are designed to be taught in short, daily instruction segments to help students gain the most from music and transfer that knowledge to other parts of the curriculum. The lessons, a master degree project, were developed to support the Utah music…

  15. Initiation and maintenance of oral ethanol self-administration in female Sprague-Dawley rats.

    PubMed

    Neill, J C; Domeney, A M; Costall, B

    1994-01-01

    Group-housed female Sprague-Dawley rats were trained to self-administer 5% ethanol (v/v) in a large self-administration chamber (100 x 40 x 40 cm) following three different initiation methods. The procedures were 1) an ethanol injection procedure, 2) a sucrose substitution procedure, and 3) a prandial drinking technique. Only the prandial drinking method served to maintain responding for ethanol in the absence of water deprivation or sweetening of the alcohol solution. Rats trained using this technique showed a large preference for 5% ethanol over water and a significant increase in locomotor activity while responding for 5% ethanol but not while responding for water. When the concentration of ethanol was increased from 1% to 32%, the amount of ethanol ingested increased up to a maximum of 1.233 +/- 0.3 g/kg of 32% ethanol, and response rates and number of ethanol deliveries followed an inverted U-shaped curve. Appreciable blood ethanol levels were detected immediately following self-administration of 8% ethanol. These results show that, in female Sprague-Dawley rats under the experimental conditions described, the prandial drinking technique was the most effective in inducing stable oral ethanol self-administration and suggest that under these conditions and in these subjects ethanol was acting as a positive reinforcer.

  16. Oral administration of kefiran exerts a bifidogenic effect on BALB/c mice intestinal microbiota.

    PubMed

    Hamet, M F; Medrano, M; Pérez, P F; Abraham, A G

    2016-01-01

    The activity of kefiran, the exopolysaccharide present in kefir grains, was evaluated on intestinal bacterial populations in BALB/c mice. Animals were orally administered with kefiran and Eubacteria, lactobacilli and bifidobacteria populations were monitored in faeces of mice at days 0, 2, 7, 14 and 21. Profiles obtained by Denaturing Gradient Gel Electrophoresis (DGGE) with primers for Eubacteria were compared by principal component analysis and clearly defined clusters, correlating with the time of kefiran consumption, were obtained. Furthermore, profile analysis of PCR products amplified with specific oligonucleotides for bifidobacteria showed an increment in the number of DGGE bands in the groups administered with kefiran. Fluorescent In Situ Hybridisation (FISH) with specific probes for bifidobacteria showed an increment of this population in faeces, in accordance to DGGE results. The bifidobacteria population was also studied on distal colon content after 0, 2 and 7 days of kefiran administration. Analysis of PCR products by DGGE with Eubacteria primers showed an increment in the number and intensity of bands with high GC content of mice administered with kefiran. Sequencing of DGGE bands confirmed that bifidobacteria were one of the bacterial populations modified by kefiran administration. DGGE profiles of PCR amplicons obtained by using Bifidobacterium or Lactobacillus specific primers confirmed that kefiran administration enhances bifidobacteria, however no changes were observed in Lactobacillus populations. The results of the analysis of bifidobacteria populations assessed on different sampling sites in a murine model support the use of this exopolysaccharide as a bifidogenic functional ingredient.

  17. Oral Administration of Cilostazol Increases Ocular Blood Flow in Patients with Diabetic Retinopathy.

    PubMed

    Hwang, Duck Jin; Shin, Joo Young; Yu, Hyeong Gon

    2017-04-01

    To investigate the effect of cilostazol on ocular hemodynamics and to determine whether the administration of cilostazol increases the ocular blood flow in patients with diabetic retinopathy. This prospective observational study investigated the effect of orally administered cilostazol on diabetic retinopathy. Before and after administration for 1 week, pulsatile ocular blood flow (POBF) and retrobulbar hemodynamics were measured using a POBF analyzer and transcranial Doppler imaging, respectively. Visual acuity, intraocular pressure, and blood pressure were also evaluated before and after treatment. Twenty-five eyes of 25 patients were included in this study. POBF increased significantly (16.8 ± 4.6 µL/sec vs. 19.6 ± 6.2 µL/sec, p < 0.001) after administration of cilostazol, while no significant change was identified in visual acuity, intraocular pressure, and blood pressure. Mean flow velocity in the ophthalmic artery as measured with transcranial Doppler imaging also increased significantly after medication (23.5 ± 5.6 cm/sec vs. 26.0 ± 6.9 cm/sec, p = 0.001). The change in POBF directly correlated with the change in mean flow velocity (r = 0.419, p = 0.007). Cilostazol was effective in increasing ocular blood flow in patients with diabetic retinopathy, possibly by modulating retrobulbar circulation.

  18. Analysis of clinical efficacy, side effects, and laboratory changes among patients with acne vulgaris receiving single versus twice daily dose of oral isotretinoin.

    PubMed

    Ahmad, Hesham M

    2015-01-01

    Acne vulgaris is a debilitating disorder and requires proper treatment. This work evaluates the clinical efficacy, side effects, and laboratory changes of serum lipids and liver function during oral isotretinoin therapy for acne vulgaris, comparing single versus twice daily dose. Fifty-eight patients with acne vulgaris were included and randomized into group I (26 patients), who received once daily dose, and group II (32 patients), who received twice daily dose of oral isotretinoin. Global acne scoring system was used to evaluate acne severity and post-treatment improvement. Both regimens resulted in highly significant clinical improvement of acne with no significant difference. However, side effects were significantly more common among patients of group I. Both regimens caused mild rise of serum cholesterol, alanine transaminase (ALT), and aspartate aminotransferase (AST) with more prominent rise of triglycerides especially with twice daily dose. Oral isotretinoin is a very effective treatment for acne vulgaris with no statistically significant difference in clinical efficacy between once and twice daily doses. However, dividing dose to twice per day might cause fewer incidence of side effects without reducing clinical efficacy. The drug causes mild clinically insignificant rise of serum cholesterol, triglycerides, AST, and ALT. © 2015 Wiley Periodicals, Inc.

  19. Effects of Administration of Fostamatinib on Blood Concentrations of an Oral Contraceptive in Healthy Female Subjects

    ClinicalTrials.gov

    2012-02-17

    Scientific Terminology Rheumatoid Arthritis, Healthy Female Volunteers, Pharmacokinetics, Oral Contraceptive, Drug-drug Interaction; Laymen Terminology Level of Oral Contraceptive in Blood, Oral Contraceptive, Rheumatoid Arthritis, Drug -Drug Interaction

  20. Do self-efficacy and depression predict oral impacts on daily performances across time? A 2-yr follow-up of students in Tanzania.

    PubMed

    Åstrøm, Anne N; Lie, Stein A; Mbawalla, Hawa

    2016-08-01

    This study aimed to assess the longitudinal validity of the oral impacts on daily performance (OIDP) and to identify psychosocial determinants, in terms of self-efficacy and depressive symptoms, of the OIDP across time. Following conceptual frameworks of oral health, it was hypothesized that sociodemographic, clinical, and psychosocial factors predict oral impacts across time at both population- averaged and person-specific levels. Whether the effects of sociodemographic and clinical factors were accounted for, totally or in part, by psychosocial factors were also investigated. Self administered questionnaires and oral clinical examinations at baseline (2009) and follow-up (2011) were completed by 1,714 and 727 secondary school students, respectively. Generalized equalized equations and a random intercept model were used to account for the dependency in repeated observations. Mean OIDP change scores were negative (worsened) among those who reported worsened self-reported oral health. Psychosocial, clinical, and sociodemographic factors were independently associated with oral impacts at the population-averaged and person-specific levels. Mediation of sociodemographic and clinical variables according to psychosocial variables was not observed. Satisfactory longitudinal evaluative properties of the OIDP, and independent effects of psychosocial factors on oral impacts across time, were confirmed among secondary school students in Tanzania. © 2016 Eur J Oral Sci.

  1. Effect of oral administration of probiotics on growth performance, apparent nutrient digestibility and stress-related indicators in Holstein calves.

    PubMed

    Zhang, R; Zhou, M; Tu, Y; Zhang, N F; Deng, K D; Ma, T; Diao, Q Y

    2016-02-01

    This study aimed to investigate the effect of dietary supplementation with Lactobacillus plantarum and Bacillus subtilis on growth performance, apparent nutrient digestibility and stress-related indicators in dairy calves. Twenty-four neonatal Holstein calves were randomly allocated to three treatments: a basal diet with no supplementation (control), the basal diet supplemented with 1.7 × 10(10) CFU per head per day (CFU/h.d) of L. plantarum GF103 (LB group) or the basal diet supplemented with a mixture of L. plantarum GF103 (1.7 × 10(10) CFU/h.d) and B. subtilis B27 (1.7 × 10(8) CFU/h.d) (LBS group). Dry matter intake (DMI), average daily gain (ADG), feed conversation ratio (FCR), apparent digestibility of nutrients and stress-related indicators were measured in this trail. The result indicated that no significant differences were observed in DMI or ADG (p > 0.05), but the FCR was improved in the LB group over the first 12 weeks (p > 0.05). The apparent digestibility of nutrients was not altered by probiotics in week 6 (p > 0.05), but the apparent digestibility of total phosphorus was significantly greater in the LB and LBS groups in week 8 (p > 0.05); additionally, an increase in the apparent digestibility of crude protein was detected in the LBS group (p > 0.05). Oral administration of L. plantarum alone improved the T-lymphocyte transformation rate on days 58 and 62 (p > 0.05), while adding the mixture of L. plantarum and B. subtilis increased the T-lymphocyte transformation rate (p > 0.05) but decreased the content of cortisol on day 58 (p > 0.05). No significant differences were detected between the LB and LBS groups in growth performance, apparent digestibility of nutrients and stress-related indicators (p > 0.05). The results suggested that oral administration of L. plantarum improved growth performance, nutrient digestibility and relieved weaning stress in calves, but no additional effect was obtained by supplementation with B. subtilis. Journal of

  2. Effect of PUFAs Oral Administration on the Amount of Apoptotic Caspases Enzymes in Gastric Cancer Patients Undergoing Chemotherapy.

    PubMed

    Dolatkhah, Homayun; Movahedian, Ahmad; Somi, Mohammad-Hossein; Aghaei, Mahmud; Samadi, Naser; Mirza-Aghazade, Ahmad; Esfahani, Ali

    2017-01-01

    Gastric cancer is the fourth most common cancer and the second cause of death in the world. According to the studies, the gastric cancer is relatively sensitive to chemotherapy. The aim of this study was to investigate the association of oral administer PUFAs with Caspase enzymes in patients with gastric cancer under chemotherapy. This study was a Clinical Trial in which the target group consisted of the patients recognized with gastric cancer for the first time and cured under chemotherapy. Thirty-four patients were selected and categorized randomly into two groups. The case group included the patients taking PUFAs along with chemotherapeutic agent. In these patients, chemotherapy started with Cis-Platin plus PUFAs supplement in the scale of 3600 mg daily and in three courses. In control group, the individuals were under the same chemotherapy protocol without PUFAs. Biopsy samples from tumor were taken from the patients before and after chemotherapy. Levels of mRNA and protein expression of caspase 3, 8, 9 were measured in biopsy samples by Real-Time PCR and Frozen Section methods. The levels of apoptosis were determined using DNA-damage colorimetric assay. In the case group, caspase 3 showed a significant increase in both gene and protein expression levels after administration of PUFAs supplement in comparison with those of the control group (p=0.006 for gene, p=0.001 for protein). PUFAs induced caspase-9 gene expression level in these patients (p<0.0001). Caspase-9 protein level also revealed a marked elevation when PUFAs were administered along with chemotherapeutic agent (p<0.0001). DNA damage in gastric tissue from the patients under PUFAs treatment plus Cis-Platin was significantly higher than that of control group (p=0.003). PUFAs showed no significant changes in caspase-8 both at the gene and protein levels in the patients. According to the results of present study, it appears that oral administration of PUFAs can elevate the efficacy of chemotherapy agent

  3. Oral Administration of Methylphenidate Blocks the Effect of Cocaine on Uptake at the Drosophila Dopamine Transporter

    PubMed Central

    2013-01-01

    Although our understanding of the actions of cocaine in the brain has improved, an effective drug treatment for cocaine addiction has yet to be found. Methylphenidate binds the dopamine transporter and increases extracellular dopamine levels in mammalian central nervous systems similar to cocaine, but it is thought to elicit fewer addictive and reinforcing effects owing to slower pharmacokinetics for different routes of administration between the drugs. This study utilizes the fruit fly model system to quantify the effects of oral methylphenidate on dopamine uptake during direct cocaine exposure to the fly CNS. The effect of methylphenidate on the dopamine transporter has been explored by measuring the uptake of exogenously applied dopamine. The data suggest that oral consumption of methylphenidate inhibits the Drosophila dopamine transporter and the inhibition is concentration dependent. The peak height increased to 150% of control when cocaine was used to block the dopamine transporter for untreated flies but only to 110% for methylphenidate-treated flies. Thus, the dopamine transporter is mostly inhibited for the methylphenidate-fed flies before the addition of cocaine. The same is true for the rate of the clearance of dopamine measured by amperometry. For untreated flies the rate of clearance changes 40% when the dopamine transporter is inhibited with cocaine, and for treated flies the rate changes only 10%. The results were correlated to the in vivo concentration of methylphenidate determined by CE-MS. Our data suggest that oral consumption of methylphenidate inhibits the Drosophila dopamine transporter for cocaine uptake, and the inhibition is concentration dependent. PMID:23402315

  4. Silver ions are responsible for memory impairment induced by oral administration of silver nanoparticles.

    PubMed

    Węsierska, M; Dziendzikowska, K; Gromadzka-Ostrowska, J; Dudek, J; Polkowska-Motrenko, H; Audinot, J N; Gutleb, A C; Lankoff, A; Kruszewski, M

    2018-06-15

    Increasing use of silver nanoparticles (AgNPs) results in increased human exposure. AgNPs are able to cross brain-blood barrier and are a risk factor for the brain. Thus, we hypothesized that AgNPs exposure might affect hippocampal dependent memory, which required cognitive coordination processes. To verify the assumption, in this study we evaluated the effects of orally administered bovine serum albumin (BSA)-coated AgNPs on spatial memory, which engage cognitive coordination processes for on-going stimuli segregation. Rats following 28 days of oral administration with 1 mg/kg (n = 10) or 30 mg/kg (n = 10) BSA-AgNPs or saline, a control groups (n = 10, n = 8), were tested with an active place avoidance task in the Carousel Maze test. The study revealed significant impairment of long- and short-term memory, irrespectively of dose of AgNPs, whereas non-cognitive activity was on a similar level. We found significantly higher content of silver in the hippocampus in comparison to the lateral cortex. No silver was found in the cerebellum and the frontal cortex. The nanoSIMS analysis reveal a weak signal of silver in the hippocampus of AgNPs treated animals that should be attributed to the presence of silver in ionic form rather than AgNPs. Our findings indicate that oral exposure to a low dose AgNPs induces detrimental effect on memory and cognitive coordination processes. The presence of silver ions rather than AgNPs in different brain regions, in particular the hippocampus, suggests crucial role of silver ions in AgNPs-induced impairment of the higher brain functions. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Comparative absorption, distribution, and excretion of titanium dioxide and zinc oxide nanoparticles after repeated oral administration.

    PubMed

    Cho, Wan-Seob; Kang, Byeong-Cheol; Lee, Jong Kwon; Jeong, Jayoung; Che, Jeong-Hwan; Seok, Seung Hyeok

    2013-03-26

    The in vivo kinetics of nanoparticles is an essential to understand the hazard of nanoparticles. Here, the absorption, distribution, and excretion patterns of titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles following oral administration were evaluated. Nanoparticles were orally administered to rats for 13 weeks (7 days/week). Samples of blood, tissues (liver, kidneys, spleen, and brain), urine, and feces were obtained at necropsy. The level of Ti or Zn in each sample was measured using inductively coupled plasma-mass spectrometry. TiO₂ nanoparticles had extremely low absorption, while ZnO nanoparticles had higher absorption and a clear dose-response curve. Tissue distribution data showed that TiO₂ nanoparticles were not significantly increased in sampled organs, even in the group receiving the highest dose (1041.5 mg/kg body weight). In contrast, Zn concentrations in the liver and kidney were significantly increased compared with the vehicle control. ZnO nanoparticles in the spleen and brain were minimally increased. Ti concentrations were not significantly increased in the urine, while Zn levels were significantly increased in the urine, again with a clear dose-response curve. Very high concentrations of Ti were detected in the feces, while much less Zn was detected in the feces. Compared with TiO₂ nanoparticles, ZnO nanoparticles demonstrated higher absorption and more extensive organ distribution when administered orally. The higher absorption of ZnO than TiO₂ nanoparticles might be due to the higher dissolution rate in acidic gastric fluid, although more thorough studies are needed.

  6. Oral administration of kefiran induces changes in the balance of immune cells in a murine model.

    PubMed

    Medrano, Micaela; Racedo, Silvia M; Rolny, Ivanna S; Abraham, Analía G; Pérez, Pablo F

    2011-05-25

    The aim of the present study was to evaluate the effect of the oral administration of kefiran on the balance of immune cells in a murine model. Six week old BALB/c mice were treated with kefiran (300 mg/L) for 0, 2 and 7 days. Kefiran treatment increased the number of IgA+ cells in lamina propria after 2 and 7 days. Percentage of B220+/MHCII(high) cells in mesenteric lymph nodes (2 days) and Peyer's patches (7 days) was higher compared to untreated control mice. An increase of macrophages (F4/80+ cells) was observed in lamina propria and peritoneal cavity (2 and 7 days). In contrast, at day 7, macrophage population decreased in Peyer's patches. These results show the ability of kefiran to modify the balance of immune cells in intestinal mucosa. This property could be highly relevant for the comprehension of the probiotic effect attributed to kefir.

  7. Tissue distribution comparison between healthy and fatty liver rats after oral administration of hawthorn leaf extract.

    PubMed

    Yin, Jingjing; Qu, Jianguo; Zhang, Wenjie; Lu, Dongrui; Gao, Yucong; Ying, Xixiang; Kang, Tingguo

    2014-05-01

    Hawthorn leaves, a well-known traditional Chinese medicine, have been widely used for treating cardiovascular and fatty liver diseases. The present study aimed to investigate the therapeutic basis treating fatty liver disease by comparing the tissue distribution of six compounds of hawthorn leaf extract (HLE) in fatty liver rats and healthy rats after oral administration at first day, half month and one month, separately. Therefore, a sensitive and specific HPLC method with internal standard was developed and validated to determine chlorogenic acid, vitexin-4''-O-glucoside, vitexin-2''-O-rhamnoside, vitexin, rutin and hyperoside in the tissues including heart, liver, spleen, kidney, stomach and intestine. The results indicated that the six compounds in HLE presented some bioactivity in treating rat fatty liver as the concentrations of the six compounds varied significantly in inter- and intragroup comparisons (healthy and/or fatty liver group). Copyright © 2013 John Wiley & Sons, Ltd.

  8. Synthesis of LHRH antagonists suitable for oral administration via the vitamin B12 uptake system.

    PubMed

    Russell-Jones, G J; Westwood, S W; Farnworth, P G; Findlay, J K; Burger, H G

    1995-01-01

    Conjugates have been synthesized between vitamin B12 and two lysyl derivatives of the LHRH antagonist, ANTIDE. Lys6-ANTIDE and Lys8-ANTIDE were both found to have similar activities to the native analogue in the in vitro pituitary cell assay. The in vitro bioactivity of the VB12-ANTIDE conjugates was preserved following linkage using a number of spacers; however, the in vivo bioactivity was lost. In order to produce conjugates which had similar in vivo bioactivity to the native analogue, it was necessary to link the VB12 to the ANTIDE analogues using thiol cleavable spacers. The resultant conjugates had similar activity to ANTIDE both in vitro and in vivo and were also found to be much more water soluble than ANTIDE. These VB12-ANTIDE conjugates show potential utility as water soluble ANTIDE analogues for parenteral use and are protease resistant LHRH antagonist analogues suitable for uptake from the intestine via the VB12-transport system following oral administration.

  9. Managing ulcerative colitis by increasing hydrogen production via oral administration of Acarbose.

    PubMed

    Zhu, Jian-Hong; Zhang, De-Qing; Chen, Wei-Chang

    2013-01-01

    The objective of the study was to investigate ulcerative colitis management through oral administration of acarbose. Acarbose has gained importance as a drug used widely to treat Diabetes Mellitus Type 2,as it acts on the small intestine by competitively inhibiting enzymes that delay the release of glucose from complex carbohydrates, thereby specifically reducing postprandial glucose excursion. The main side-effect of treatment with Acarbose, flatulence, occurs when undigested carbohydrates are fermented by colonic bacteria, resulting in considerable amounts of hydrogen. We found that the enteric benefits of Acarbose are partly due to be their ability to neutralise oxidative stress via increased production of H₂ in the gastrointestinal tract. Therefore, some symptoms of ulcerative colitis in human beings can be ameliorated by Acarbose.

  10. Toxicity in three dogs from accidental oral administration of a topical endectocide containing moxidectin and imidacloprid.

    PubMed

    See, A M; McGill, S E; Raisis, A L; Swindells, K L

    2009-08-01

    Three dogs were presented with a history of oral administration of a topical endectocide containing imidacloprid and moxidectin. They were diagnosed with imidacloprid and moxidectin intoxication, having ingested doses ranging from 7.5 to 1.4 mg/kg of imidacloprid and 1.9 to 2.8 mg/kg of moxidectin. The three dogs were affected to different degrees of severity, but all displayed signs of ataxia, generalised muscle tremors, paresis, hypersalivation and disorientation. Temporary blindness occurred in two cases. The three dogs were tested for the presence of the multi-drug resistance 1 gene deletion, which can cause an increased sensitivity to the toxic effects of moxidectin, and were found to be negative. Treatment included gastrointestinal decontamination, intravenous fluid therapy and benzodiazepines to control muscle tremors. All three dogs made a complete recovery within 48 h of ingestion.

  11. [Purification of arsenic-binding proteins in hamster plasma after oral administration of arsenite].

    PubMed

    Wang, Wenwen; Zhang, Min; Li, Chunhui; Qin, Yingjie; Hua, Naranmandura

    2013-01-01

    To purify the arsenic-binding proteins (As-BP) in hamster plasma after a single oral administration of arsenite (iAs(III)). Arsenite was given to hamsters in a single dose. Three types of HPLC columns, size exclusion, gel filtration and anion exchange columns, combined with an inductively coupled argon plasma mass spectrometer (ICP MS) were used to purify the As-BP in hamster plasma. SDS-PAGE was used to confirm the arsenic-binding proteins at each purification step. The three-step purification process successfully separated As-BP from other proteins (ie, arsenic unbound proteins) in hamster plasma. The molecular mass of purified As-BP in plasma was approximately 40-50 kD on SDS-PAGE. The three-step purification method is a simple and fast approach to purify the As-BP in plasma samples.

  12. Morning administration of oral methamphetamine dose-dependently disrupts nighttime sleep in recreational stimulant users.

    PubMed

    Herrmann, Evan S; Johnson, Patrick S; Bruner, Natalie R; Vandrey, Ryan; Johnson, Matthew W

    2017-09-01

    Use of amphetamine-type stimulants (e.g., methamphetamine) is associated with acute sleep disruptions. No prior reports have characterized the acute effects of methamphetamine on sleep using polysomnography, the gold standard for objective sleep monitoring. Recreational stimulant users (n=19) completed a baseline assessment, which included questionnaires assessing demographic and substance use characteristics, and the Pittsburgh Sleep Quality Index (PSQI), which assesses sleep quality over the past month. Participants were administered 0mg (placebo), 20mg, or 40mg oral methamphetamine at 08:15h on study days, using a double-blind, randomized, within-subjects design. Sleep was monitored using polysomnography from 22:20 that evening until 06:15 the following morning. PSQI scores indicated more than half of participants reported poor sleep quality at baseline. Methamphetamine dose-dependently increased sleep latency, and decreased total sleep time, sleep efficiency, time in NREM 2 sleep, number of REM periods, and total time in REM sleep. Sleep under placebo conditions was consistent with what would be expected from healthy adults. Morning oral administration of methamphetamine produces robust disruptions in nighttime sleep. Future research should examine relations between stimulant use and sleep disruption in naturalistic settings, with regard to both stimulant abuse and licit prescription use. Copyright © 2017. Published by Elsevier B.V.

  13. Successful treatment of Marburg virus with orally administrated T-705 (Favipiravir) in a mouse model.

    PubMed

    Zhu, Wenjun; Zhang, Zirui; He, Shihua; Wong, Gary; Banadyga, Logan; Qiu, Xiangguo

    2018-03-01

    Filoviruses, such as Marburg and Ebola viruses, cause severe disease in humans with high case fatality rates and are therefore considered biological threat agents. To date, no licensed vaccine or therapeutic exists for their treatment. T-705 (favipiravir) is a pyrazinecarboxamide derivative that has shown broad antiviral activity against a number of viruses and is clinically licenced in Japan to treat influenza. Here we report the efficacy of T-705 against Marburg virus infection in vitro and in vivo. Notably, oral administration of T-705 beginning one or two days post-infection and continuing for eight days resulted in complete survival of mice that had been intraperitoneally infected with mouse-adapted Marburg virus (variant Angola). Moreover, lower doses of T-705 and higher doses administered later during infection (day 3 or 4 post-infection) showed partial efficacy, with at least half the infected mice surviving. Accordingly, we observed reductions in infectious virus particles and virus RNA levels following drug treatment that appeared to correlate with survival. Our findings suggest that T-705 may be an effective therapeutic against Marburg virus and might be especially promising for use in the event of an outbreak, where it could be orally administered quickly and safely even after exposure. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  14. Residual veterinary antibiotics in pig excreta after oral administration of sulfonamides.

    PubMed

    Qiu, Jinrong; Zhao, Tao; Liu, Qingyun; He, Jinhua; He, Dechun; Wu, Genyi; Li, Yongtao; Jiang, Chengai; Xu, Zhencheng

    2016-04-01

    Sulfonamides (SAs) are applied widely as feed additives in the farming of livestock and poultry. It can lead to the excretion of large amounts of SAs in manure and result in persistent environmental pollution. We evaluated the fate of four SAs, sulfamerazine (SM1), sulfachloropyridazine (SCP), sulfadimoxine (SDM') and sulfaquinoxaline (SQ), from oral administration to excretion in urine and feces in pigs. The four SAs were added to homemade feed to make them reach the required concentration gradient, which were 0, 50 and 100 mg/kg (low, normal and high concentrations, respectively). In different treatments, excretions of the four SAs were 35.68-86.88 %. With regard to total excretion, the order was SQ > SCP > SM1 > SDM' for all treatments. The concentration of SAs in the feed had significant effects on the amount of the four SAs excreted every day. The concentration of SAs in feces and in the urine for different treatments was 15.03-26.55 and 14.54-69.22 %, respectively. In each treatment, excretions of SCP, SDM' and SQ in feces were lower than that in urine. The four SAs remained longer in urine than in feces. Excretions in urine and feces were lower if SAs were administered orally rather than by injection.

  15. Prevention of bacteremia in dogs undergoing dental scaling by prior administration of oral clindamycin or chlorhexidine oral rinse.

    PubMed

    Bowersock, T L; Wu, C C; Inskeep, G A; Chester, S T

    2000-03-01

    Dogs with periodontitis were used to determine the efficacy of an oral regimen of clindamycin versus chlorhexidine acetate oral rinse in reducing the total number of bacteria and the incidence of bacteremia before and after dental scaling. Aerobic and anaerobic bacteria, isolated from blood and gingival swab cultures, were identified to genus using an automated system.

  16. Effects of oral administration of tilmicosin on pulmonary inflammation in piglets experimentally infected with Actinobacillus pleuropneumoniae.

    PubMed

    Nerland, Erin M; LeBlanc, Justin M; Fedwick, Jason P; Morck, Douglas W; Merrill, John K; Dick, Paul; Paradis, Marie-Anne; Buret, Andre G

    2005-01-01

    To determine the effects of oral administration of tilmicosin in piglets experimentally infected with Actinobacillus pleuropneumoniae. Forty 3-week-old specific-pathogen free piglets. Piglets were assigned to 1 of 4 groups as follows: 1) uninfected sham-treated control piglets; 2) infected untreated piglets that were intratracheally inoculated with 10(7) CFUs of A pleuropneumoniae; 3) infected treated piglets that were intratracheally inoculated with A pleuropneumoniae and received tilmicosin in feed (400 ppm [microg/g]) for 7 days prior to inoculation; or 4) infected treated piglets that were intratracheally inoculated with A pleuropneumoniae and received chlortetracycline (CTC) in feed (1100 ppm [microg/gl) for 7 days prior to inoculation. Bronchoalveolar lavage (BAL) fluid and lung tissue specimens of piglets for each group were evaluated at 3 or 24 hours after inoculation. For each time point, 4 to 6 piglets/group were studied. Feeding of CTC and tilmicosin decreased bacterial load in lungs of infected piglets. Tilmicosin delivered in feed, but not CTC, enhanced apoptosis in porcine BAL fluid leukocytes. This was associated with a decrease in LTB4 concentrations in BAL fluid of tilmicosin-treated piglets, compared with untreated and CTC-treated piglets, and also with a significant decrease in the number of pulmonary lesions. Tilmicosin inhibited infection-induced increases in rectal temperatures, as measured in untreated and CTC-treated piglets. Pulmonary neutrophil infiltration and prostaglandin E2 concentrations in the BAL fluid were not significantly different among groups at any time. Oral administration of tilmicosin to infected piglets induces apoptosis in BAL fluid leukocytes and decreases BAL fluid LTB4 concentrations and inflammatory lung lesions.

  17. Tear film concentrations of doxycycline following oral administration in ophthalmologically normal dogs.

    PubMed

    Collins, Sean P; Labelle, Amber L; Dirikolu, Levent; Li, Zhong; Mitchell, Mark A; Hamor, Ralph E

    2016-09-01

    OBJECTIVE To determine tear film concentrations of doxycycline in ophthalmologically normal dogs following oral doxycycline administration. DESIGN Crossover study. ANIMALS 10 privately owned dolichocephalic or mesaticephalic dogs free of ophthalmic disease. PROCEDURES Dogs were randomly assigned to receive doxycycline hyclate first at 5 mg/kg (2.3 mg/lb) or 10 mg/kg (4.5 mg/lb), PO, every 12 hours for 5 days, beginning on day 1. Doxycycline was administered 1 hour prior to feeding. Tear samples were collected from days 1 through 10 approximately 3 hours after the morning dose was administered. Following a 3-week washout period, dogs received the alternative dose in the same conditions. Doxycycline concentration in tear samples from 1 eye (same eye used for both sessions) was measured via liquid chromatography-mass spectrometry and compared between the 2 doxycycline doses. RESULTS Doxycycline was detected in tear samples of all dogs from days 1 through 10 for both doxycycline doses. Median peak doxycycline concentrations for the 5 mg/kg and 10 mg/kg doses were 2.19 ng/mL on day 3 and 4.32 ng/mL on day 4, respectively. Concentrations differed significantly with time, but this difference was not influenced by dose, dose order, or eye. A significant positive correlation was identified between doxycycline concentration and body weight (r = 0.22). CONCLUSIONS AND CLINICAL RELEVANCE Detectable doxycycline concentrations were achieved in the tear film of ophthalmologically normal dogs following oral administration of doxycycline at 5 or 10 mg/kg, every 12 hours. Dose had no significant effect on tear film concentration of the drug.

  18. Extemporaneous procedures for dissolving risedronate tablets for oral administration and for feeding tubes.

    PubMed

    Dansereau, Richard J; Crail, Debbie J

    2005-01-01

    Risedronate (Actonel, Procter & Gamble Pharmaceuticals) is commercially available only as film-coated tablets. Extemporaneous procedures for dissolving tablets for feeding tubes and for preparation of an oral liquid have not previously been evaluated. To evaluate procedures for dissolving risedronate sodium tablets for administration in liquid form and drug recovery following dissolution in cups and following passage through different types of feeding tubes. Tablets (5 and 35 mg) were individually dispersed in 2 oz of water. After 2 minutes, the solution was stirred for 30 seconds, dispensed, and rinsed with an additional 4 oz of water. The sample was filtered and analyzed by HPLC. Ten replicates were performed using the various cups. Gastrostomy and nasoenteric tubes were flushed with 1 oz of water. Individual tablets were dispersed in 2 oz of water; after 2 minutes, the solution was stirred for 30 seconds and poured through the tube and flushed with 1 oz of water. Samples were filtered and analyzed by HPLC. Ten replicates were performed for each type of feeding tube. For cups, the mean amount of drug recovered ranged from 95.7% to 100.5% of the label claim, with a relative standard deviation (RSD) range of 1.1-6.3%. For gastrostomy and nasoenteric tubes, the mean amount of drug recovered ranged from 98.3% to 101.9% of label claim, with an RSD range of 0.9-3.3%. A simple and accurate procedure was developed for dissolving risedronate tablets in water to prepare a liquid formulation for administration orally or through feeding tubes.

  19. Oral Administration of Pentoxifylline Reduces Endometriosis-Like Lesions in a Nude Mouse Model.

    PubMed

    Perelló, Maria; González-Foruria, Iñaki; Castillo, Paola; Martínez-Florensa, Mario; Lozano, Francisco; Balasch, Juan; Carmona, Francisco

    2017-06-01

    Recent reports consider endometriosis to be an immunological disorder, thus suggesting potential efficacy of immunomodulators for its treatment. The aim of this study was to assess the effects of oral administration of pentoxifylline on endometriosis-like lesions in a heterologous mice model. Human endometrial tissue obtained from women (n = 5) undergoing surgery for benign conditions was implanted in nude female mice (n = 30). The animals were distributed into 3 experimental groups receiving: saline 0.1 mL/d (control, group 1); pentoxifylline 100 mg/kg/d (group 2), and pentoxifylline 200 mg/kg/d (group 3). After 28 days, the number of implants and the total volume of surgically extracted tissue were recorded. Immunohistochemical analysis was performed to assess the area of endometriosis and vascularization of endometriosis-like lesions. Cytokine levels in peritoneal fluid samples were measured. Macroscopic quantification showed a trend to dose-dependent reduction in the number of the endometriosis-like lesions after 28 days. The volume was significantly reduced in group 3 versus group 2 and controls (399.10 ± 120.68 mm 3 vs 276.75 ± 94.30 mm 3 and 145.33 ± 38.20 mm 3 , respectively; P = .04). Similarly, the mean area of endometriosis was significantly lower in group 3 (0.12 ± 0.08 mm 2 ) versus group 2 (1.35 ± 0.43 mm 2 ) and control (2.84 ± 0.60 mm 2 ; P = .001). Vascularization and cytokine levels were also reduced posttreatment. Our results suggest that the oral administration of pentoxifylline may be an alternative to current therapies for endometriosis. Nonetheless, further studies are required.

  20. A Novel, Ecologically Relevant, Highly Preferred, and Non-invasive Means of Oral Substance Administration for Rodents

    PubMed Central

    Sobolewski, Marissa; Allen, Joshua L.; Morris-Schaffer, Keith; Klocke, Carolyn; Conrad, Katherine; Cory-Slechta, Deborah A.

    2017-01-01

    Prenatal stress and nutrition are well-known to alter a broad range of physiological systems, notably metabolic, endocrine and neurobehavioral function. Commonly used methods for oral administration of xenobiotics can, by acting as a stressor or altering normal nutrition intake, alter these physiological systems as well. Taken together, oral administration methods may unintentionally introduce confounding physiological effects that can mask or enhance toxicity of xenobiotics, particularly if they share biological targets. Consequently, it should be preferable to develop alternative methods without these potential confounds. The aim of this study was to determine the suitability of mealworms as an alternative treat-based method to deliver xenobiotics via the orogastric route. Accurate oral administration is contingent on motivation and preference; mice reliably preferred mealworms over wafer cookie treats. Further, ingestion of wafer cookies significantly increased mouse blood glucose levels, whereas unaltered mealworms produced no such change. Mealworms functioned effectively to orally administer glucose, as glucose-spiked mealworms produced a rise in blood glucose equivalent to the ingestion of the wafer cookie. Mealworms did not interfere with the physiological function of orally administered d-amphetamine, as both mealworm and oral gavage administered d-amphetamine showed similar alterations in locomotor behavior (mice did not fully consume d-amphetamine-dosed cookies and thus could not be compared). Collectively, the findings indicate that mealworms are a preferred and readily consumed treat, which importantly mimics environmental-relevant nutritional intake, and mealworms per se do not alter glucose metabolic pathways. Additionally, mealworms accurately delivered xenobiotics into blood circulation and did not interfere with the physiological function of administered xenobiotics. Thus mealworm-based oral administration may be a preferable and accurate route of

  1. A novel, ecologically relevant, highly preferred, and non-invasive means of oral substance administration for rodents.

    PubMed

    Sobolewski, Marissa; Allen, Joshua L; Morris-Schaffer, Keith; Klocke, Carolyn; Conrad, Katherine; Cory-Slechta, Deborah A

    2016-01-01

    Prenatal stress and nutrition are well-known to alter a broad range of physiological systems, notably metabolic, endocrine and neurobehavioral function. Commonly used methods for oral administration of xenobiotics can, by acting as a stressor or altering normal nutrition intake, alter these physiological systems as well. Taken together, oral administration methods may unintentionally introduce confounding physiological effects that can mask or enhance toxicity of xenobiotics, particularly if they share biological targets. Consequently, it should be preferable to develop alternative methods without these potential confounds. The aim of this study was to determine the suitability of mealworms as an alternative treat-based method to deliver xenobiotics via the orogastric route. Accurate oral administration is contingent on motivation and preference; mice reliably preferred mealworms over wafer cookie treats. Further, ingestion of wafer cookies significantly increased mouse blood glucose levels, whereas unaltered mealworms produced no such change. Mealworms functioned effectively to orally administer glucose, as glucose-spiked mealworms produced a rise in blood glucose equivalent to the ingestion of the wafer cookie. Mealworms did not interfere with the physiological function of orally administered d-amphetamine, as both mealworm and oral gavage administered d-amphetamine showed similar alterations in locomotor behavior (mice did not fully consume d-amphetamine-dosed cookies and thus could not be compared). Collectively, the findings indicate that mealworms are a preferred and readily consumed treat, which importantly mimics environmental-relevant nutritional intake, and mealworms per se do not alter glucose metabolic pathways. Additionally, mealworms accurately delivered xenobiotics into blood circulation and did not interfere with the physiological function of administered xenobiotics. Thus mealworm-based oral administration may be a preferable and accurate route of

  2. Cost-effectiveness of exenatide twice daily vs insulin glargine as add-on therapy to oral antidiabetic agents in patients with type 2 diabetes in China.

    PubMed

    Gu, Shuyan; Wang, Xiaoyong; Qiao, Qing; Gao, Weiguo; Wang, Jian; Dong, Hengjin

    2017-12-01

    To estimate the long-term cost-effectiveness of exenatide twice daily vs insulin glargine once daily as add-on therapy to oral antidiabetic agents (OADs) for Chinese patients with type 2 diabetes (T2DM). The Cardiff Diabetes Model was used to simulate disease progression and estimate the long-term effects of exenatide twice daily vs insulin glargine once daily. Patient profiles and treatment effects required for the model were obtained from literature reviews (English and Chinese databases) and from a meta-analysis of 8 randomized controlled trials comparing exenatide twice daily with insulin glargine once daily add-on to OADs for T2DM in China. Medical expenditure data were collected from 639 patients with T2DM (aged ≥18 years) with and without complications incurred between January 1, 2014 and December 31, 2015 from claims databases in Shandong, China. Costs (2014 Chinese Yuan [¥]) and benefits were estimated, from the payers' perspective, over 40 years at a discount rate of 3%. A series of sensitivity analyses were performed. Patients on exenatide twice daily + OAD had a lower predicted incidence of most cardiovascular and hypoglycaemic events and lower total costs compared with those on insulin glargine once daily + OAD. A greater number of quality-adjusted life years (QALYs; 1.94) at a cost saving of ¥117 706 gained was associated with exenatide twice daily vs insulin glargine once daily. (i.e. cost saving of ¥60 764/QALY) per patient. In Chinese patients with T2DM inadequately controlled by OADs, exenatide twice daily is a cost-effective add-on therapy alternative to insulin glargine once daily, and may address the problem of an excess of medical needs resulting from weight gain and hypoglycaemia in T2DM treatment. © 2017 John Wiley & Sons Ltd.

  3. Tissue distribution and elimination after oral and intravenous administration of different titanium dioxide nanoparticles in rats

    PubMed Central

    2014-01-01

    Objective The aim of this study was to obtain kinetic data that can be used in human risk assessment of titanium dioxide nanomaterials. Methods Tissue distribution and blood kinetics of various titanium dioxide nanoparticles (NM-100, NM-101, NM-102, NM-103, and NM-104), which differ with respect to primary particle size, crystalline form and hydrophobicity, were investigated in rats up to 90 days post-exposure after oral and intravenous administration of a single or five repeated doses. Results For the oral study, liver, spleen and mesenteric lymph nodes were selected as target tissues for titanium (Ti) analysis. Ti-levels in liver and spleen were above the detection limit only in some rats. Titanium could be detected at low levels in mesenteric lymph nodes. These results indicate that some minor absorption occurs in the gastrointestinal tract, but to a very limited extent. Both after single and repeated intravenous (IV) exposure, titanium rapidly distributed from the systemic circulation to all tissues evaluated (i.e. liver, spleen, kidney, lung, heart, brain, thymus, reproductive organs). Liver was identified as the main target tissue, followed by spleen and lung. Total recovery (expressed as % of nominal dose) for all four tested nanomaterials measured 24 h after single or repeated exposure ranged from 64-95% or 59-108% for male or female animals, respectively. During the 90 days post-exposure period, some decrease in Ti-levels was observed (mainly for NM-100 and NM-102) with a maximum relative decrease of 26%. This was also confirmed by the results of the kinetic analysis which revealed that for each of the investigated tissues the half-lifes were considerable (range 28–650 days, depending on the TiO2-particle and tissue investigated). Minor differences in kinetic profile were observed between the various particles, though these could not be clearly related to differences in primary particle size or hydrophobicity. Some indications were observed for an

  4. Evaluation of analgesic effect and absorption of buprenorphine after buccal administration in cats with oral disease.

    PubMed

    Stathopoulou, Thaleia-Rengina; Kouki, Maria; Pypendop, Bruno H; Johnston, Atholl; Papadimitriou, Serafeim; Pelligand, Ludovic

    2017-09-01

    Objectives The objective of this study was to evaluate the analgesic effect and absorption of buprenorphine after buccal administration in cats with oral disease. Methods Six adult client-owned cats with chronic gingivostomatitis (weighing 5.1 ± 1.1 kg) were recruited for a randomised, prospective, blinded, saline-controlled, crossover study. Pain scores, dental examination, stomatitis score and buccal pH measurement were conducted on day 1 under sedation in all cats. On day 2, animals were randomised into two groups and administered one of the two treatments buccally (group A received buprenorphine 0.02 mg/kg and group B received 0.9% saline) and vice versa on day 3. Pain scores and food consumption were measured at 30, 90 and 360 mins after the administration of buprenorphine. Blood samples were taken at the same time and plasma buprenorphine concentration was measured by liquid chromatography-mass spectrometry. Data were statistically analysed as non-parametric and the level of significance was set as P <0.05. Results There were no major side effects after buprenorphine administration. Buccal pH values ranged between 8.5 and 9.1 and the stomatitis disease activity index between 10 and 22 (17.8 ± 4.5) with the scale ranging from 0-30. The maximum buprenorphine plasma concentration (14.8 ng/ml) was observed 30 mins after administration and there was low inter-individual variability. There was a significant difference between baseline pain scores compared with pain scores after buprenorphine ( P <0.05 ) and between the saline and buprenorphine group at 30 mins ( P = 0.04) and 90 mins ( P = 0.04). There was also a significant effect of the stomatitis index on the pain score. Regarding the pharmacokinetic parameters, cats with stomatitis showed lower bioavailability and shorter absorption half-life after buccal administration of buprenorphine compared with normal cats in previous studies. Conclusions and relevance Buccal administration of buprenorphine in cats with

  5. Plasma disposition and faecal excretion of oxfendazole, fenbendazole and albendazole following oral administration to donkeys.

    PubMed

    Gokbulut, Cengiz; Akar, Ferda; McKellar, Quintin A

    2006-07-01

    Fenbendazole (FBZ), oxfendazole (fenbendazole sulphoxide, FBZSO), and albendazole (ABZ) were administered orally to donkeys at 10mg/kg bodyweight. Blood and faecal samples were collected from 1 to 120 h post-treatment. The plasma and faecal samples were analysed by high performance liquid chromatography (HPLC). The parent molecule and its sulphoxide and sulphone (FBZSO(2)) metabolites did not reach detectable concentrations in any plasma samples following FBZ administration. ABZ was also not detected in any plasma samples, but its sulphoxide and sulphone metabolites were detected, demonstrating that ABZ was completely metabolised by first-pass mechanisms in donkeys. Maximum plasma concentrations (C(max)) of FBZSO (0.49microg/mL) and FBZSO(2) (0.60microg/mL) were detected at (t(max)) 5.67 and 8.00h, respectively, following administration of FBZSO. The area under the curve (AUC) of the sulphone metabolite (10.33microg h/mL) was significantly higher than that of the parent drug FBZSO (5.17microg h/mL). C(max) of albendazole sulphoxide (ABZSO) (0.08g/mL) and albendazole sulphone (ABZSO(2)) (0.04microg/mL) were obtained at 5.71 and 8.00h, respectively, following ABZ administration. The AUC of the sulphoxide metabolite (0.84microg h/mL) of ABZ was significantly higher than that of the sulphone metabolite (0.50microg h/mL). The highest dry-faecal concentrations of parent molecules were detected at 32, 34 and 30h for FBZSO, FBZ and ABZ, respectively. The sulphide metabolite was significantly higher than the parent molecule after FBZSO administration. The parent molecule was predominant in the faecal samples following FBZ administration. After ABZ administration, the parent molecule was significantly metabolised, probably by gastrointestinal microflora, to its sulphoxide metabolite (ABZSO) that showed a similar excretion profile to the parent molecule in the faecal samples. The AUC of the parent FBZ was significantly higher than that of FBZSO and ABZ in faeces. It is

  6. Can oral fluid cannabinoid testing monitor medication compliance and/or cannabis smoking during oral THC and oromucosal Sativex administration?

    PubMed

    Lee, Dayong; Karschner, Erin L; Milman, Garry; Barnes, Allan J; Goodwin, Robert S; Huestis, Marilyn A

    2013-06-01

    We characterize cannabinoid disposition in oral fluid (OF) after dronabinol, synthetic oral Δ(9)-tetrahydrocannabinol (THC), and Sativex, a cannabis-extract oromucosal spray, and evaluate whether smoked cannabis relapse or Sativex compliance can be identified with OF cannabinoid monitoring. 5 and 15 mg synthetic oral THC, low (5.4 mg THC, 5.0 mg cannabidiol (CBD)) and high (16.2 mg THC, 15.0 mg CBD) dose Sativex, and placebo were administered in random order (n=14). Oral fluid specimens were collected for 10.5 h after dosing and analyzed for THC, CBD, cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH). After oral THC, OF THC concentrations decreased over time from baseline, reflecting residual THC excretion from previously self-administered smoked cannabis. CBD and CBN also were rarely detected. After Sativex, THC, CBD and CBN increased greatly, peaking at 0.25-1 h. Median CBD/THC and CBN/THC ratios were 0.82-1.34 and 0.04-0.06, respectively, reflecting cannabinoids' composition in Sativex. THCCOOH/THC ratios within 4.5 h post Sativex were ≤ 1.6 pg/ng, always lower than after oral THC and placebo. THCCOOH/THC ratios increased throughout each dosing session. Lack of measurable THC, CBD and CBN in OF following oral THC, and high OF CBD/THC ratios after Sativex distinguish oral and sublingual drug delivery routes from cannabis smoking. Low THCCOOH/THC ratios suggest recent Sativex and smoked cannabis exposure. These data indicate that OF cannabinoid monitoring can document compliance with Sativex pharmacotherapy, and identify relapse to smoked cannabis during oral THC medication but not Sativex treatment, unless samples were collected shortly after smoking. Published by Elsevier Ireland Ltd.

  7. Can oral fluid cannabinoid testing monitor medication compliance and/or cannabis smoking during oral THC and oromucosal Sativex administration?

    PubMed Central

    Lee, Dayong; Karschner, Erin L.; Milman, Garry; Barnes, Allan J.; Goodwin, Robert S.; Huestis, Marilyn A.

    2012-01-01

    OBJECTIVES We characterize cannabinoid disposition in oral fluid (OF) after Dronabinol, synthetic oral Δ9-tetrahydrocannabinol (THC), and Sativex, a cannabis-extract oromucosal spray, and evaluate whether smoked cannabis relapse or Sativex compliance can be identified with OF cannabinoid monitoring. METHODS 5 and 15 mg synthetic oral THC, low (5.4 mg THC, 5.0 mg cannabidiol (CBD)) and high (16.2 mg THC, 15.0 mg CBD) dose Sativex, and placebo were administered in random order (n=14). Oral fluid specimens were collected for 10.5h after dosing and analyzed for THC, CBD, cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH). RESULTS After oral THC, OF THC concentrations decreased over time from baseline, reflecting residual THC excretion from previously self-administered smoked cannabis. CBD and CBN also were rarely detected. After Sativex, THC, CBD and CBN increased greatly, peaking at 0.25–1h. Median CBD/THC and CBN/THC ratios were 0.82–1.34 and 0.04–0.06, respectively, reflecting cannabinoids’ composition in Sativex. THCCOOH/THC ratios within 4.5h post Sativex were ≤1.6 pg/ng, always lower than after oral THC and placebo. THCCOOH/THC ratios increased throughout each dosing session. CONCLUSIONS Lack of measurable THC, CBD and CBN in OF following oral THC, and high OF CBD/THC ratios after Sativex distinguish oral and sublingual drug delivery routes from cannabis smoking. Low THCCOOH/THC ratios suggest recent Sativex and smoked cannabis exposure. These data indicate that OF cannabinoid monitoring can document compliance with Sativex pharmacotherapy, and identify relapse to smoked cannabis during oral THC medication but not Sativex treatment, unless samples were collected shortly after smoking. PMID:23146820

  8. Effects of oral administration of caffeine and D-ribose on mental fatigue.

    PubMed

    Ataka, Suzuka; Tanaka, Masaaki; Nozaki, Satoshi; Mizuma, Hiroshi; Mizuno, Kei; Tahara, Tsuyoshi; Sugino, Tomohiro; Shirai, Tomoko; Kajimoto, Yoshitaka; Kuratsune, Hirohiko; Kajimoto, Osami; Watanabe, Yasuyoshi

    2008-03-01

    We examined the effects of administering two different candidate antifatigue substances, caffeine and D-ribose, on mental fatigue. In a double-blinded, placebo-controlled, three-way crossover design, 17 healthy volunteers were randomized to oral caffeine (200 mg/d), D-ribose (2000 mg/d), or placebo for 8 d. As fatigue-inducing mental tasks, subjects performed a 30-min Uchida-Kraepelin psychodiagnostic test and a 30-min advanced trail-making test on four occasions. During the tasks, the task performance of the caffeine group was better than that of the placebo group. However, after the fatigue-inducing tasks, although subjective perception of fatigue, motivation, or sleepiness was not significantly different, plasma branched-chain amino acid levels in the caffeine group were lower than those of the placebo group. Administration of D-ribose had no effect. Because plasma branched-chain amino acid levels are decreased by mental fatigue, these results suggest that administration of caffeine improved task performance through the enhancement of central nervous system activity without increasing the sensation of fatigue. However, further decreases in branched-chain amino acid levels indicate that caffeine might promote deeper fatigue than placebo. Unfortunately, research subsequent to our study design has shown that D-ribose dosing higher than we used is needed to see a clinical effect and therefore no conclusions can be made from this study as to the efficacy of D-ribose.

  9. Arsenic Speciation and Accumulation in Selected Organs after Oral Administration of Rice Extracts in Wistar Rats.

    PubMed

    Lewchalermvong, Kittima; Rangkadilok, Nuchanart; Nookabkaew, Sumontha; Suriyo, Tawit; Satayavivad, Jutamaad

    2018-03-28

    Despite its nutritional values, rice also contains arsenic. There has been increasing concern about health implications associated with exposure to arsenic through rice consumption. The present study evaluated arsenic accumulation and its speciation in selected organs of Wistar rats after 28 day repeated oral administrations of polished or unpolished rice and their control arsenic compounds (sodium arsenite or dimethylarsinic acid; DMA). Only the treatment of sodium arsenite (2 μg/kg body weight), significantly increased total arsenic concentrations in blood when compared to the distilled water control group. In all groups, total arsenic concentrations were highest in kidney (1.54-1.90 mg/kg) followed by liver (0.85-1.52 mg/kg), and the predominant arsenic form in these organs was DMA. However, there was no significant difference in arsenic accumulation in the measured organs among the control and rice-treated groups. Therefore, the repeated 28 day administration of arsenic-contaminated rice did not cause significant arsenic accumulation in the animal organs.

  10. Degradation rate of praziquantel and fenbendazole in rainbow trout following oral administration.

    PubMed

    Soukupova-Markova, Zdenka; Doubkova, Veronika; Marsalek, Petr; Svobodova, Zdenka; Papezikova, Ivana; Lang, Stepan; Navratil, Stanislav; Palikova, Miroslava

    2015-01-01

    The aim of this study was to evaluate and compare the rate of degradation and elimination of praziquantel and fenbendazole antiparasitics following oral administration to salmonids. In addition, we determine whether the length of the legal withdrawal period is sufficient for complete elimination of antiparasitic residue from the body. The use of these drugs in fish is currently considered off-label and data on degradation are not available for rainbow trout. The model species for this experiment was the rainbow trout (Oncorhynchus mykiss) and praziquantel and fenbendazole were chosen for experimental therapy. Both drugs were administered into the gastrointestinal tract using a stomach tube. Concentrations of fenbendazole and praziquantel were established through high performance liquid chromatography-tandem mass spectrometry. Our results show that concentrations of praziquantel and fenbendazole reach their maximum in the body within 24 hours of administration, with concentrations dropping sharply over the following 24 hours. With one exception, when trace amounts of both substances were found in blood plasma, the drugs were completely degraded and eliminated from the body by the end of the experiment (corresponding to 497.6 degree days). Praziquantel and fenbendazole both show a high rate of degradation and elimination from fish. As both substances were eliminated from the body within the required withdrawal period (i.e. within 500 degree days) they can be safely used based on current knowledge of their therapeutic effect for treating helminth infections.

  11. [The Influence of Preoperative Oral Carbohydrate Administration on Perioperative Blood Sugar Levels and Patients' Satisfaction].

    PubMed

    Morita, Tomotaka; Kita, Takashi; Masada, Kyoko; Nagata, Takako; Sasaki, Shigeta

    2016-06-01

    After introducing preoperative oral carbohydrate as a part of enhanced recovery after surgery (ERAS) protocols, we assessed the influence of carbohydrate administration on the perioperative blood sugar levels (BS), the variation of vital signs and patients' satisfaction. After IRB's approval and obtaining patients' consent, patients were divided into two groups; taking carbohydrate (Group AW) or not (Group NAW). Anesthesia was induced and maintained with total intravenous anesthesia using propofol, remifentanil and rocuronium. We measured BS six times during perioperative period. We also compared blood pressures and heart rates during induction of anesthesia. Moreover, we carried out questionnaire surveys about degree of satisfaction for ERAS among patients and nurses. Heart rates were significantly higher in Group AW (P < 0.05), but there were no significant difference in blood pressures or BS between the groups. Patients in Group AW had more anxiety for surgeries (P = 0.003), but more than 85% of patients and nurses were satisfied with carbohydrates. The carbohydrate administration had little influence on the perioperative vital signs. However, we gained high reputations from patients and paramedics.

  12. The renal excretion of iodine following oral administration of Gastrografin to domestic cats.

    PubMed

    Allan, G S; Wentworth, R A; Rendano, V T; Meunier, P C; Marmor, M

    1980-01-01

    Serum and urinary levels of iodine were determined in six cats before and after oral administration of Gastrografin. Iodine was identified by gamma spectrometry after the specimens had been subjected to neutron activation. Peak serum iodine levels, compared to undetectable preadministration levels in five of the six cats, ranged from 8.0 to 50.7 micrograms/ml 1 to 2 hours after Gastrografin administration. Twenty-four hour cumulative urinary excretion of iodine represented 0.9 to 4.08% of this element calculated to be in Gastrografin. Pharmacokinetic analysis of the serum concentrations using the one-compartment open model resulted in an estimate of ka, the fraction of Gastrografin dose absorbed per unit time, of 2.24 hr-1 (95% CL = -5.4, 7.7) and an estimate of ke, the fraction of the dose eliminated per unit time, of 0.10 hr-1 (95 % CL = -0.01, 0.21). Analysis of urinary elimination rates also yielded ke = 0.10 hr-1 (95% CL = 0.01, 0.18). At necropsy the gastrointestinal tract of each cat was normal.

  13. Usefulness of Daily Fractionated Administration of Wortmannin Combined With γ-Ray Irradiation in Terms of Local Tumor Response and Lung Metastasis

    PubMed Central

    Masunaga, Shin-ichiro; Sakurai, Yoshinori; Tanaka, Hiroki; Suzuki, Minoru; Kondo, Natsuko; Narabayashi, Masaru; Tano, Keizo; Maruhashi, Akira; Ono, Koji

    2013-01-01

    Background To evaluate the usefulness of fractionated administration of wortmannin combined with γ-ray irradiation in terms of local tumor response and lung metastatic potential, referring to the response of intratumor quiescent (Q) cells. Methods B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously given 5-bromo-2’-deoxyuridine (BrdU) to label all proliferating (P) cells. The tumor-bearing mice then received γ-ray irradiation after wortmannin treatment through a single or 4 consecutive daily intraperitoneal administrations up to a total dose of 4 mg/kg in combination with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH). Immediately after the irradiation, cells from some tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (= P + Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumor-bearing mice, 17 days after irradiation, macroscopic lung metastases were enumerated. Results Wortmannin raised the sensitivity of Q cells more remarkably than the total cell population in both single and daily administrations. Daily administration of wortmannin elevated the sensitivity of both the total and Q cell populations, but especially the total cell population, compared with single administration. Daily administration, especially combined with MTH, decreased the number of lung metastases. Conclusion Daily fractionated administration of wortmannin in combination with γ-ray irradiation was thought to be more promising than single administration because of its potential to enhance local tumor response and repress lung metastatic potential. PMID:29147327

  14. Effect of Oral Administration of Metronidazole or Prednisolone on Fecal Microbiota in Dogs

    PubMed Central

    Ohno, Koichi; Horigome, Ayako; Odamaki, Toshitaka; Tsujimoto, Hajime

    2014-01-01

    Gastrointestinal microbiota have been implicated in the pathogenesis of various gastrointestinal disorders in dogs, including acute diarrhea and chronic enteropathy. Metronidazole and prednisolone are commonly prescribed for the treatment of these diseases; however, their effects on gastrointestinal microbiota have not been investigated. The objective of this study was to evaluate the effects of these drugs on the gastrointestinal microbiota of dogs. Metronidazole was administered twice daily at 12.5 mg/kg to a group of five healthy dogs, and prednisolone at 1.0 mg/kg daily to a second group of five healthy dogs for 14 days. Fecal samples were collected before and after administration (day 0 and 14), and 14 and 28 days after cessation (day 28 and 42). DNA was extracted, and the bacterial diversity and composition of each sample were determined based on 16S ribosomal RNA (rRNA) gene sequences using next-generation sequencing (Illumina MiSeq). In the group administered metronidazole, bacterial diversity indices significantly decreased at day 14, and recovered after the cessation. Principal coordinates analysis and hierarchical dendrogram construction based on unweighted and weighted UniFrac distance matrices revealed that bacterial composition was also significantly altered by metronidazole at day 14 compared with the other time points. The proportions of Bacteroidaceae, Clostridiaceae, Fusobacteriaceae, Lachnospiraceae, Ruminococcaceae, Turicibacteraceae, and Veillonellaceae decreased, while Bifidobacteriaceae, Enterobacteriaceae, Enterococcaceae, and Streptococcaceae increased at day 14 and returned to their initial proportions by day 42. Conversely, no effect of prednisolone was observed on either the bacterial diversity or composition. Reducing pathogenic bacteria such as Fusobacteria and increasing beneficial bacteria such as Bifidobacterium through the administration of metronidazole may be beneficial for promoting gastrointestinal health; however, further

  15. Changes in the concentrations of vitamin E analogs and their metabolites in rat liver and kidney after oral administration

    PubMed Central

    Kiyose, Chikako; Saito, Kazuki; Yachi, Rieko; Muto, Chie; Igarashi, Osamu

    2015-01-01

    Vitamin E analog, such as α- and γ-tocopherol, can undergo ω-oxidation without cleavage of the chroman ring, and this pathway is responsible for generation of the major urinary vitamin E metabolite, carboxyethyl hydroxychroman. However, it is still unclear how carboxyethyl hydroxychroman is changed in various tissues after vitamin E intake. We therefore investigated changes in the concentrations of α- and γ-tocopherol and their metabolites in rat liver and kidney. The concentration of α-tocopherol in rat liver increased until 6 h after oral administration, and then decreased. The change in the concentration of α-carboxyethyl hydroxychroman in rat liver in the α-Toc group slowly increased until 12 h after oral administration. Cytochrome P450 3A1 mRNA expression significantly increased from 12 h after the start of α-tocopherol administration. The change in the concentration of γ-carboxyethyl hydroxychroman in rat liver in the γ-Toc group markedly increased until 12 h after oral administration. On the other hand, γ-carboxyethyl hydroxychroman in rat kidney showed greater accumulation than α-carboxyethyl hydroxychroman from 3 h to 24 h after oral administration. From these results, we considered that γ-carboxyethyl hydroxychroman formed in the liver continues to be released into the bloodstream and is transported to the kidney rapidly. PMID:25759520

  16. Effect of oral calcium bolus administration on milk production, concentrations of minerals and metabolites in serum, early-lactation health status, and reproductive performance of Holstein dairy cows.

    PubMed

    Jahani-Moghadam, M; Chashnidel, Y; Teimouri-Yansari, A; Mahjoubi, E; Dirandeh, E

    2018-05-01

    To determine the effects of oral Ca bolus administration in the early postpartum period of cows on milk yield and composition, blood metabolites, early-lactation health status, and reproductive performance. Multiparous Holstein dry cows (n=66) with a mean parity of 3.1 (SD 0.35) were fed a diet with a positive dietary cation-anion difference (DCAD) prior to calving. They were randomly assigned to receive no treatment (Control; n=33) or two oral Ca boluses (n=33, 45 g of Ca per bolus); one was administered immediately after calving (Day 0) and the second 24 hours (±30 minutes) later. Blood samples were collected at calving, and on Days 2 and 7 to determine concentrations in serum of Ca, P, Mg, glucose, non-esterified fatty acids (NEFA), and β-hydroxybutyric acid (BHBA). Milk yield was recorded daily and milk composition was determined weekly from calving until 28 day postpartum. Health and outcomes were determined during the first 30 days postpartum and reproductive outcomes to 180 days postpartum. Mean milk yields and composition over the first month of lactation were similar between cows in the two treatment groups (p>0.1). Mean concentrations of Ca in serum were not different between treatment groups on Day 0, but were higher on Day 2 for cows that received oral Ca boluses (1.77 (SE 0.07)) compared with Control cows (1.54 (SE 0.08)) (p=0.04). Concentrations in serum of P, Mg, glucose, NEFA and ΒHBA did not differ between treatment groups on any day of measurement. Fewer cows that received oral Ca were diagnosed with hypocalcaemia (total concentrations of Ca in serum <1.5 mmol/L) by Day 2 (2/33; 6%) compared with Control cows (12/33; 36%) (p=0.01). There was no difference in the prevalence of other health outcomes between treatment groups. The proportion of cows conceiving to first insemination was greater in cows that received an oral Ca bolus (19/29; 65%) than Control cows (12/29; 41%) (p=0.01). Oral Ca bolus administration increased concentrations of Ca

  17. Effects of oral powder electrolyte administration on packed cell volume, plasma chemistry parameters, and incidence of colic in horses participating in a 6-day 162-km trail ride

    PubMed Central

    Walker, Wade T.; Callan, Robert J.; Hill, Ashley E.; Tisher, Kelly B.

    2014-01-01

    This study evaluated the effects of administering oral powder electrolytes on packed cell volume (PCV), plasma chemistry parameters, and incidence of colic in horses participating on a 6-day 162-km trail ride in which water was not offered ad libitum. Twenty-three horses received grain with powder electrolytes daily while 19 control horses received grain only. Horses were ridden approximately 32 km a day at a walk or trot. Packed cell volume and plasma chemistry parameters were analyzed daily. Episodes of colic were diagnosed and treated by a veterinarian unaware of treatment group allocation. Blood parameters and incidence of colic were compared between treatment groups. Electrolyte administration did not alter PCV or plasma chemistry parameters compared to controls. The incidence of colic was significantly higher in treated horses (P = 0.05). Oral powder electrolytes did not enhance hydration status or electrolyte homeostasis and may be associated with colic in horses participating on long distance trail rides similar to this model. PMID:25082992

  18. Can oral 5-aminosalicylic acid be administered once daily in the treatment of mild-to-moderate ulcerative colitis? A meta-analysis of randomized-controlled trials.

    PubMed

    Zhu, Ying; Tang, Ren-Kuan; Zhao, Peng; Zhu, Shi-sheng; Li, Yong-guo; Li, Jian-bo

    2012-05-01

    Several trials have demonstrated that oral delayed-release mesalamine might be administered once daily. We aimed to conduct a meta-analysis to investigate this. A comprehensive and multiple-source literature search was carried out. Only randomized-controlled trials (RCTs) were investigated by comparing a once daily-dosing regime with a divided (twice or thrice daily)-dosing regime of oral delayed-release mesalamine formulations for induction or maintenance of remission in patients with mild-to-moderate ulcerative colitis. The quality of RCTs was assessed using the Jadad scores. Meta-analysis of pooled odds ratios was carried out using Review Manager 5.1. Nine RCTs were finally included. With regard to meta-analyses for induction trials, there were no significant differences for all comparisons between the once daily and the divided groups, including maintenance of just clinical remission (P=0.52) and just endoscopic remission (P=0.23), maintenance of combined clinical and endoscopic remission (P=0.78), and the overall incidence of adverse events (P=0.61). With regard to meta-analyses for maintenance trials, there were also no significant differences for all comparisons between once daily and divided groups, including maintenance of just clinical remission (P=0.73) and just endoscopic remission (P=0.43), maintenance of combined clinical and endoscopic remission (P=0.43), the overall incidence of adverse events (P=0.12) as well as compliance with the prescribed medication (P=0.34). The present work showed that oral delayed-release mesalazine administered as a single or a divided dose demonstrated a good safety profile, which was well tolerated and effective as either maintenance or induction treatment. High clinical and/or endoscopic remission rates can be achieved with once-daily dosing.

  19. Acute oral administration of the novel, competitive and selective glucocorticoid receptor antagonist ORG 34517 reduces the severity of ethanol withdrawal and related hypothalamic- pituitary-adrenal axis activation

    PubMed Central

    Reynolds, Anna R.; Saunders, Meredith A.; Brewton, Honoree’ W.; Winchester, Sydney R.; Elgumati, Ibrahim S.; Prendergast, Mark A.

    2015-01-01

    Background The development of ethanol dependence is associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis and activation of type II glucocorticoid receptors (GR). These effects may contribute to withdrawal-associated anxiety, craving and relapse to drinking. The present studies examined acute and oral administration of the novel, selective and competitive GR antagonist ORG 34517 on the severity of ethanol withdrawal. Methods Adult, male Sprague-Dawley rats were administered ethanol (4g/kg/i.g.) twice daily for 5 days followed by 2 days of withdrawal for 1, 2 or 3 consecutive cycles. Blood ethanol levels (BELs) were determined at 0930 on Day 4 of each week, while blood corticosterone levels (BCLs) were obtained at 1100 hrs on the first day of each ethanol withdrawal. During early withdrawal, subjects received oral administration of ORG 345617 (60 mg/kg/i.g.) or a placebo and withdrawal was monitored. Results Peak BELs of 225.52 mg/dl were observed during the third week. Withdrawal from three cycles of the regimen produced marked behavioral abnormalities (e.g. aggression, rigidity, and hypoactivity) and significant increases in BCLs of ethanol-dependent subjects. Acute, oral administration of ORG 34517 during early withdrawal significantly reduced both the severity of ethanol withdrawal, as reflected in reduced rigidity, aggression, and hypoactivity, and elevations in BCL without producing any sedative-like effects. Conclusions The present findings demonstrate that repeated ethanol exposure and withdrawal is associated with significant behavioral abnormalities and dysregulation of HPA axis activation. Further these data suggest that selective GR antagonists should be further considered as putative pharmacotherapies for treatment of ethanol dependence. PMID:26143299

  20. Acute oral administration of the novel, competitive and selective glucocorticoid receptor antagonist ORG 34517 reduces the severity of ethanol withdrawal and related hypothalamic-pituitary-adrenal axis activation.

    PubMed

    Reynolds, Anna R; Saunders, Meredith A; Brewton, Honoree' W; Winchester, Sydney R; Elgumati, Ibrahim S; Prendergast, Mark A

    2015-09-01

    The development of ethanol dependence is associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis and activation of type II glucocorticoid receptors (GR). These effects may contribute to withdrawal-associated anxiety, craving and relapse to drinking. The present studies examined acute and oral administration of the novel, selective and competitive GR antagonist ORG 34517 on the severity of ethanol withdrawal. Adult, male Sprague-Dawley rats were administered ethanol (4g/kg/i.g.) twice daily for 5 days followed by 2 days of withdrawal for 1, 2 or 3 consecutive cycles. Blood ethanol levels (BELs) were determined at 0930 on Day 4 of each week, while blood corticosterone levels (BCLs) were obtained at 11:00hours on the first day of each ethanol withdrawal. During early withdrawal, subjects received oral administration of ORG 345617 (60mg/kg/i.g.) or a placebo and withdrawal was monitored. Peak BELs of 225.52mg/dl were observed during the third week. Withdrawal from three cycles of the regimen produced marked behavioral abnormalities (e.g., aggression, rigidity, and hypoactivity) and significant increases in BCLs of ethanol-dependent subjects. Acute, oral administration of ORG 34517 during early withdrawal significantly reduced both the severity of ethanol withdrawal, as reflected in reduced rigidity, aggression, and hypoactivity, and elevations in BCL without producing any sedative-like effects. The present findings demonstrate that repeated ethanol exposure and withdrawal is associated with significant behavioral abnormalities and dysregulation of HPA axis activation. Further these data suggest that selective GR antagonists should be further considered as putative pharmacotherapies for treatment of ethanol dependence. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Oral and intraperitoneal administration of phosphorothioate oligodeoxynucleotides leads to control of Cryptosporidium parvum infection in neonatal mice.

    PubMed

    Barrier, Mathieu; Lacroix-Lamandé, Sonia; Mancassola, Roselyne; Auray, Gaël; Bernardet, Nelly; Chaussé, Anne-Marie; Uematsu, Satoshi; Akira, Shizuo; Laurent, Fabrice

    2006-05-15

    Neonates are particularly vulnerable to infections, in part because of the incomplete development of their immune system. Recent advances in immunostimulatory treatments based on conserved microbial components led us to assess the potential of oligodeoxynucleotides (ODNs) for decreasing the sensitivity of neonates to Cryptosporidium parvum infection. Neonate mice were treated orally or intraperitoneally (ip) with CpG ODNs or non-CpG ODNs 24 h before C. parvum infection, and parasite load and cytokine up-regulation were evaluated. CpG ODN 1668 and non-CpG ODN 1668 administered orally, as well as CpG ODN 1668 administered ip, induced an 80%-95% decrease in intestinal parasite load 6 days after infection. Intraperitoneal and oral pretreatment with CpG ODN 1668 led to a strong initial up-regulation of cytokines and CD69 messenger RNA in the intestine and a decrease in parasite load by a Toll-like receptor 9 (TLR9)-dependent mechanism. By contrast, oral administration of non-CpG ODN 1668 decreased parasite load by a TLR9-independent mechanism. The control of neonatal C. parvum infection by ip or oral administration of ODNs is feasible by 2 different mechanisms: (1) the well-known interaction involving CpG/TLR9, leading to the production of cytokines and lymphocyte activation, and (2) a new unknown mechanism that is independent of TLR9 and effective orally.

  2. Morphine and Codeine in Oral Fluid after Controlled Poppy Seed Administration

    PubMed Central

    Concheiro, Marta; Newmeyer, Matthew N.; da Costa, Jose Luiz; Flegel, Ron; Gorelick, David A.; Huestis, Marilyn A.

    2014-01-01

    Opiates are an important drug class in drug testing programs. Ingestion of poppy seeds containing morphine and codeine can yield positive opiate tests and mislead result interpretation in forensic and clinical settings. Multiple publications evaluated urine opiate concentrations following poppy seed ingestion, but only 2 addressed oral fluid (OF) results; neither provided the ingested morphine and codeine dosage. We administered two 45g raw poppy seed doses, each containing 15.7mg morphine and 3.1mg codeine, 8h apart to 17 healthy adults. All OF specimens were screened by on-site OF immunoassay Draeger DrugTest 5000, and confirmed with OF collected with Oral-Eze® device and quantified by liquid chromatography tandem mass spectrometry (1μg/L morphine and codeine limits of quantification). Specimens (n=459) were collected before and up to 32h after the first dose. All specimens screened positive 0.5h after dosing and remained positive for 0.5-13h at Draeger 20μg/L morphine cutoff. Maximum OF morphine and codeine concentrations (Cmax) were 177 and 32.6μg/L, with times to Cmax (Tmax) of 0.5-1h and 0.5-2.5h post-dose, respectively. Windows of detection after the second dose extended at least 24h for morphine and to 18h for codeine. After both doses, the last morphine positive OF result was 1h with 40μg/L 2004 proposed US Substance Abuse and Mental Health Services Administration cutoff, and 0.5h with 95μg/L cutoff, recently recommended by the Driving Under the Influence of Drugs and Medicines project. Positive OF morphine results are possible 0.5-1h after ingestion of 15.7mg of morphine in raw poppy seeds, depending upon the cutoff employed. PMID:25345619

  3. Preparation, characterization and bioavailability by oral administration of O/W curcumin nanoemulsions stabilized with lysophosphatidylcholine.

    PubMed

    Chávez-Zamudio, Rubi; Ochoa-Flores, Angélica A; Soto-Rodríguez, Ida; Garcia-Varela, Rebeca; García, Hugo Sergio

    2017-09-20

    Curcumin is the main and most abundant bioactive component in Curcuma longa L. with documented properties in the prevention and treatment of chronic degenerative and infectious diseases. However, curcumin has low solubility in aqueous media, hence low bioavailability when administered orally. The use of nanoemulsions as carriers can provide a partial solution to bioavailability restrictions. In our study, O/W nanoemulsions of curcumin were prepared using lysophosphatidylcholine, a phospholipid with proven emulsification capacity; nevertheless, such qualities have not been previously reported in the preparation of nanoemulsions. Lysophosphatidylcholine was obtained by enzymatic removal of one fatty acid residue from phosphatidylcholine. The objective of our work was to formulate stable curcumin nanoemulsions and evaluate their bioavailability in BALB/c mice plasma after oral administration. Formulated nanoemulsions had a droplet size mean of 154.32 ± 3.10 nm, a polydispersity index of 0.34 ± 0.07 and zeta potential of -10.43 ± 1.10 mV; stability was monitored for 12 weeks. Lastly, in vivo pharmacokinetic parameters, using BALB/c mice, were obtained; namely, C max of 610 ± 65.0 μg mL -1 and T max of 2 h. Pharmacokinetic data revealed a higher bioavailability of emulsified as opposed to free curcumin. Research regarding other potential emulsifiers that may provide better health benefits and carry nano-encapsulated bioactive compounds more effectively, is necessary. This study provides important data on the preparation and design of nanoencapsulated Curcumin using lysophosphatidylcholine as an emulsifier.

  4. Metabolism and disposition of N,N-dimethyltryptamine and harmala alkaloids after oral administration of ayahuasca.

    PubMed

    Riba, Jordi; McIlhenny, Ethan H; Valle, Marta; Bouso, José Carlos; Barker, Steven A

    2012-01-01

    Ayahuasca is an Amazonian psychotropic plant tea obtained from Banisteriopsis caapi, which contains β-carboline alkaloids, chiefly harmine, harmaline and tetrahydroharmine. The tea usually incorporates the leaves of Psychotria viridis or Diplopterys cabrerana, which are rich in N,N-dimethyltryptamine (DMT), a psychedelic 5-HT(2A/1A/2C) agonist. The β-carbolines reversibly inhibit monoamine-oxidase (MAO), effectively preventing oxidative deamination of the orally labile DMT and allowing its absorption and access to the central nervous system. Despite increased use of the tea worldwide, the metabolism and excretion of DMT and the β-carbolines has not been studied systematically in humans following ingestion of ayahuasca. In the present work, we used an analytical method involving high performance liquid chromatography (HPLC)/electrospray ionization (ESI)/selected reaction monitoring (SRM)/tandem mass spectrometry(MS/MS) to characterize the metabolism and disposition of ayahuasca alkaloids in humans. Twenty-four-hour urine samples were obtained from 10 healthy male volunteers following administration of an oral dose of encapsulated freeze-dried ayahuasca (1.0 mg DMT/kg body weight). Results showed that less than 1% of the administered DMT dose was excreted unchanged. Around 50% was recovered as indole-3-acetic acid but also as DMT-N-oxide (10%) and other MAO-independent compounds. Recovery of DMT plus metabolites reached 68%. Harmol, harmalol, and tetrahydroharmol conjugates were abundant in urine. However, recoveries of each harmala alkaloid plus its O-demethylated metabolite varied greatly between 9 and 65%. The present results show the existence in humans of alternative metabolic routes for DMT other than biotransformation by MAO. Also that O-demethylation plus conjugation is an important but probably not the only metabolic route for the harmala alkaloids in humans. Copyright © 2012 John Wiley & Sons, Ltd.

  5. Pharmacokinetics of doxycycline in laying hens after intravenous and oral administration.

    PubMed

    Yang, F; Si, H B; Wang, Y Q; Zhao, Z S; Zhou, B H; Hao, X Q

    2016-08-01

    The pharmacokinetics of doxycycline in laying hens was investigated after a single intravenous (IV) or an oral (PO) dose at 20 mg/kg body weight. The concentrations of doxycycline in plasma samples were determined by high-performance liquid chromatography with an ultraviolet detector, and pharmacokinetic parameters were calculated using a compartmental model method. The disposition of doxycycline after one single IV injection was best described by a two-compartment open model and the main pharmacokinetic parameters were as follows: volume of distribution (Vd) was 865.15 ± 127.64 ml/kg, distribution rate constant (α) was (2.28 ± 0.38) 1/h, elimination rate constant (β) was 0.08 ± 0.02 1/h and total body clearance (Cl) was104.11 ± 18.32 ml/h/kg, while after PO administration, the concentration versus time curve was best described by a one-compartment open model and absorption rate constant (Ka), peak concentration (Cmax), time to reach Cmax (tmax) and absolute bioavailability (F) were 2.55 ± 1.40 1/h, 5.88 ± 0.70 μg/ml, 1.73 ± 0.75 h and 52.33%, respectively. The profile of doxycycline exhibited favourable pharmacokinetic characteristics in laying hens, such as quick absorption and slow distribution and elimination, though oral bioavailability was relatively low. A multiple-dosing regimen (a dose of 20 mg/kg/d for 3 consecutive days) of doxycycline was recommended to treat infections in laying hens. But a further study should be conducted to determine the withdrawal time of doxycycline in eggs.

  6. Clinical comparison of oral administration and viscosupplementation of hyaluronic acid (HA) in early knee osteoarthritis.

    PubMed

    Ricci, M; Micheloni, G M; Berti, M; Perusi, F; Sambugaro, E; Vecchini, E; Magnan, B

    2017-04-01

    Osteoarthritis (OA) is a progressive, chronic and degenerative joint disease characterized by a loss of articular cartilage. Treatment of OA is largely palliative based on nonsteroidal anti-inflammatory drugs, opioids and injections of steroids. Regarding conservative treatment, intra-articular injections of hyaluronic acid (HA) can play a role in early symptomatic knee OA. Between August 2015 and September 2015, sixty patients (32 males and 28 females) between 40 and 70 years old were randomly allocated into two groups: Half were treated with three weekly intra-articular injections of hyaluronic acid 1.6 % (group A), while the others were treated with Syalox 300 Plus ® (hyaluronic acid 300 mg + Boswellia serrata extract 100 mg) 1 tab/die for 20 days and afterward Syalox 150 ® (hyaluronic acid 150 mg) 1 tab/die for other 20 days (group B). All patients were evaluated clinically with American Knee Society Score (AKSS) and visual analogue scale (VAS) for the pain before the treatment and after 3 months. AKSS of the patients in both groups was significantly increased by the treatment, and VAS score was significantly reduced. In both groups, two subgroups were created with patients older than 60 years and patients younger than 60 years. Better results are reported in younger patients of group A and older subjects in group B. Despite several limitations, the results of the study have shown that HA injection and oral administration may have beneficial therapeutic effects on patients with early osteoarthritis. Different outcomes in younger and older subject suggested a combined therapy first with local infiltrations and then with oral composition.

  7. Effect of Oral Silymarin Administration on Prevention of Radiotherapy Induced Mucositis: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

    PubMed

    Elyasi, Sepideh; Hosseini, Sare; Niazi Moghadam, Mohammad Reza; Aledavood, Seyed Amir; Karimi, Gholamreza

    2016-11-01

    Mucositis is a frequent severe complication of radiation therapy in patient with head and neck cancer. Silymarin is a polyphenolic flavonoid extracted from the milk thistle that exhibits strong antioxidant and antiinflammatory activities. In this study, we evaluate silymarin efficacy in prevention of radiotherapy induced mucositis in patients with head and neck cancer, as the first human study. During this pilot, randomized, double-blinded, placebo-controlled clinical trial, the effect of oral silymarin 420 mg daily in three divided doses starting at the first day of radiotherapy for 6 weeks, on oral mucositis occurrence was assessed. Twenty-seven patients fulfilled the inclusion criteria assigned to the silymarin or placebo group. World Health Organization and National Cancer Institute-Common Terminology Criteria oral mucositis grading scale scores were recorded at baseline and weekly during these 6 weeks. The median World Health Organization and National Cancer Institute Common Terminology Criteria scores were significantly lower in silymarin group at the end of the first to sixth week (p < 0.05). The scores increased significantly in both placebo and silymarin groups during radiotherapy, but there was a delay for mucositis development and progression in silymarin group. Prophylactic administration of conventional form of silymarin tablets could significantly reduce the severity of radiotherapy induced mucositis and delay its occurrence in patients with head and neck cancer. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  8. Pharmacokinetics of total thyroxine after repeated oral administration of levothyroxine solution and its clinical efficacy in hypothyroid dogs.

    PubMed

    van Dijl, I C; Le Traon, G; van de Meulengraaf, B D A M; Burgaud, S; Horspool, L J I; Kooistra, H S

    2014-01-01

    Oral levothyroxine (l-T4 ) supplementation is commonly used to treat hypothyroid dogs. Investigate the plasma profile and pharmacokinetics of total thyroxine (tT4 ) after PO administration of a l-T4 solution and its clinical efficacy in hypothyroid dogs. Ten dogs with naturally occurring hypothyroidism. After hypothyroidism diagnosis and supplementation with l-T4 solution PO q24h at 20 μg/kg BW for minimum 4 weeks, the plasma profile and pharmacokinetics of tT4 were determined over 34 hours and the clinical condition of the dogs was evaluated. Before dosing for pharmacokinetic evaluation, mean tT4 concentration was 23 ± 9 nmol/L. l-T4 was absorbed rapidly (tmax , 5 hours), reaching a mean maximal tT4 concentration of 56 ± 11 nmol/L. The apparent terminal half-life was 11.8 hours. Clinical signs of hypothyroidism improved or resolved in all dogs after 4 weeks of treatment. The dosage of 20 μg/kg PO q24h was judged appropriate in 5 dogs, and 4 dogs required slight increases (9-16%). Twice daily treatment, with a 30% increase in dosage, was necessary for 1 dog. The pharmacokinetics of l-T4 in hypothyroid dogs was similar to that reported in healthy euthyroid dogs. Clinical and hormonal responses to l-T4 solution were rapid in all dogs. The starting dosage of 20 μg/kg PO q24h was suitable for maintenance supplementation in 50% of the dogs, minor dosage modification was required in 4 other dogs, and treatment q12h was required in 1 dog. Copyright © 2014 by the American College of Veterinary Internal Medicine.

  9. Pharmacokinetics of promethazine hydrochloride after administration of rectal suppositories and oral syrup to healthy subjects.

    PubMed

    Strenkoski-Nix, L C; Ermer, J; DeCleene, S; Cevallos, W; Mayer, P R

    2000-08-15

    The pharmacokinetics of promethazine hydrochloride after administration of rectal suppositories at three dosage strengths and oral syrup were studied. The study had an open-label, randomized, crossover design. At intervals of five to nine days, healthy volunteers were given two 12.5-mg promethazine rectal suppositories, one 25-mg suppository, one 50-mg suppository, or 50 mg (10 mL) of promethazine oral syrup. Blood samples were collected before each dose and at intervals from 0.5 to 48 hours afterward. Promethazine concentration was determined by high-performance liquid chromatography, and pharmacokinetic values were calculated with noncompartmental methods. Thirty-six subjects (18 men and 18 women) completed the study. Absorption was highly variable for all the formulations. On average, absorption was more rapid and the maximum plasma concentration (Cmax) higher for the syrup than for the suppositories. Cmax was significantly lower for the 50-mg suppository (mean, 9.04 ng/mL) than for the syrup (19.3 ng/mL). The time to Cmax (tmax) was significantly shorter for the syrup (mean, 4.4 hours) than for the suppositories (6.7-8.6 hours). There were no significant differences in dose-normalized Cmax among the three suppository treatments. Area under the concentration-versus-time curve (AUC) was comparable between the syrup and the 50-mg suppository and between the treatments with two 12.5-mg suppositories and the 25-mg suppository. Elimination profiles were similar among all treatments (mean half-life [t1/2], 16-19 hours). There were no significant differences in pharmacokinetics on the basis of sex or race. The mean relative bioavailability for the three suppository treatments ranged from 70% to 97%. Individual relative bioavailabilities ranged from 4% to 343%. The pharmacokinetics of promethazine administered in oral syrup and rectal suppositories were highly variable, but, in general, the suppositories produced a lower Cmax and later tmax than the syrup. All

  10. Review of the clinical pharmacokinetics of artesunate and its active metabolite dihydroartemisinin following intravenous, intramuscular, oral or rectal administration

    PubMed Central

    2011-01-01

    Artesunate (AS) is a clinically versatile artemisinin derivative utilized for the treatment of mild to severe malaria infection. Given the therapeutic significance of AS and the necessity of appropriate AS dosing, substantial research has been performed investigating the pharmacokinetics of AS and its active metabolite dihydroartemisinin (DHA). In this article, a comprehensive review is presented of AS clinical pharmacokinetics following administration of AS by the intravenous (IV), intramuscular (IM), oral or rectal routes. Intravenous AS is associated with high initial AS concentrations which subsequently decline rapidly, with typical AS half-life estimates of less than 15 minutes. AS clearance and volume estimates average 2 - 3 L/kg/hr and 0.1 - 0.3 L/kg, respectively. DHA concentrations peak within 25 minutes post-dose, and DHA is eliminated with a half-life of 30 - 60 minutes. DHA clearance and volume average between 0.5 - 1.5 L/kg/hr and 0.5 - 1.0 L/kg, respectively. Compared to IV administration, IM administration produces lower peaks, longer half-life values, and higher volumes of distribution for AS, as well as delayed peaks for DHA; other parameters are generally similar due to the high bioavailability, assessed by exposure to DHA, associated with IM AS administration (> 86%). Similarly high bioavailability of DHA (> 80%) is associated with oral administration. Following oral AS, peak AS concentrations (Cmax) are achieved within one hour, and AS is eliminated with a half-life of 20 - 45 minutes. DHA Cmax values are observed within two hours post-dose; DHA half-life values average 0.5 - 1.5 hours. AUC values reported for AS are often substantially lower than those reported for DHA following oral AS administration. Rectal AS administration yields pharmacokinetic results similar to those obtained from oral administration, with the exceptions of delayed AS Cmax and longer AS half-life. Drug interaction studies conducted with oral AS suggest that AS does not

  11. TISSUE DISTRIBUTION OF INORGANIC ARSENIC (AS) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (ASV)

    EPA Science Inventory

    TISSUE DISTRIBUTION OF INORGANIC ARSENIC (iAs) AND ITS METHYLATED METABOLITES IN MICE FOLLOWING ORAL ADMINISTRATION OF ARSENATE (AsV). E M Kenyon1, L M Del Razo2, and M F Hughes1. 1NHEERL, ORD, US EPA, RTP, NC, USA; 2CINVESTAV-IPN, Mexico City, Mexico.

    The relationship o...

  12. Biotransformation of the platinum drug JM216 following oral administration to cancer patients.

    PubMed

    Raynaud, F I; Mistry, P; Donaghue, A; Poon, G K; Kelland, L R; Barnard, C F; Murrer, B A; Harrap, K R

    1996-01-01

    This study evaluates the metabolic profile of JM216 [bis(acetato)ammine-dichloro(cyclohexylamine) platinum(IV)], the first orally administrable platinum complex, in plasma ultrafiltrates of 12 patients (n = 2-4 time points per patient) following different doses of drug (120, 200, 340, 420, 560 mg/m2). The biotransformation profile was evaluated by high-performance liquid chromatography (HPLC) followed by atomic absorption spectrophotometry (AA). The AA profiles were compared with those previously identified by HPLC on line with mass spectrometry (HPLC-MS) in plasma incubated with JM216. A total of six platinum peaks (Rt = 5.5, 7.2, 10.6, 12.4, 15.6, and 21.6 min, respectively) were observed in patients' plasma ultrafiltrate samples, of which only four appeared during the first 6 h post-treatment. Four of these coeluted with those observed and identified previously in plasma incubation medium. No parent JM216 was detected. The major metabolite seen in patients was the Pt II complex JM118 [cis-amminedichloro-(cyclohexylamine)platinum(II)] and was observed in all the patients. Interestingly, the second metabolite was shown to coelute with the Pt IV species JM383 [bis-acetatoammine(cyclohexylamine)dihydroxoplatinum (IV)]. Both JM118 and JM383 were identified by HPLC-MS in a clinical sample. Peak C, which was a minor product (less than 5% of the free platinum), coeluted with JM559 [bis-acetatoammine-chloro(cyclohexylalamine)hydroxoplatin um(IV)]. The cytotoxicity profile of all three metabolites in a panel of cisplatin-sensitive and -resistant human ovarian carcinoma cell lines was very close to that of the parent drug. In addition, the concentrations of JM118 reached in patients' plasma ultrafiltrate were comparable with the cytotoxic levels of the compound determined in the ovarian carcinoma panel of cell lines. Two metabolites were seen in patients but not in the in vitro incubation medium, suggesting the involvement of a possible enzymatic reaction. Thus, the

  13. Oral administration of FAK inhibitor TAE226 inhibits the progression of peritoneal dissemination of colorectal cancer

    SciTech Connect

    Hao, Hui-fang; Takaoka, Munenori; Bao, Xiao-hong

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer A novel FAK inhibitor TAE226 suppressed FAK activity in HCT116 colon cancer cells. Black-Right-Pointing-Pointer TAE226 suppressed proliferation and migration, with a modest effect on adhesion. Black-Right-Pointing-Pointer Silencing of FAK by siRNA made no obvious difference on cancer cell attachment. Black-Right-Pointing-Pointer TAE226 treatment suppressed the progression of peritoneal dissemination. Black-Right-Pointing-Pointer Oral administration of TAE226 prolonged the survival of tumor-bearing mice. -- Abstract: Peritoneal dissemination is one of the most terrible types of colorectal cancer progression. Focal adhesion kinase (FAK) plays a crucial role in the biological processes of cancer, such as cell attachment, migration, proliferation and survival, all ofmore » which are essential for the progression of peritoneal dissemination. Since we and other groups have reported that the inhibition of FAK activity exhibited a potent anticancer effect in several cancer models, we hypothesized that TAE226, a novel ATP-competitive tyrosine kinase inhibitor designed to target FAK, can prevent the occurrence and progression of peritoneal dissemination. In vitro, TAE226 greatly inhibited the proliferation and migration of HCT116 colon cancer cells, while their adhesion on the matrix surface was minimally inhibited when FAK activity and expression was suppressed by TAE226 and siRNA. In vivo, when HCT116 cells were intraperitoneally inoculated in mice, the cells could attach to the peritoneum and begin to grow within 24 h regardless of the pretreatment of cells with TAE226 or FAK-siRNA, suggesting that FAK is not essential, at least for the initial integrin-matrix contact. Interestingly, the treatment of mice before and after inoculation significantly suppressed cell attachment to the peritoneum. Furthermore, oral administration of TAE226 greatly reduced the size of disseminated tumors and prolonged survival in tumor-bearing mice

  14. Oral opioid administration and hyperalgesia in patients with cancer or chronic nonmalignant pain

    PubMed Central

    Reznikov, Igor; Pud, Dorit; Eisenberg, Elon

    2005-01-01

    Aims Previous research has reported on reduced paw withdrawal latencies to heat and mechanical stimuli after parenteral administration of opioids in animals and on increased pain sensitivity in humans subsequent to postoperative infusions of short-acting opioids or in drug addicts. The aim of the present study was to explore the possibility that oral opioid treated patients with cancer-related or chronic nonmalignant pain differ in their pain sensitivity from patients treated with non-opioid analgesics. Methods The study population consisted of 224 patients, including 142 in the opioid-treated group and 82 in the non-opioid-treated group. Pain thresholds for punctuate measured by von Frey filaments (g), mechanical pressure measured by pressure algometer (mmHg), heat stimuli measured by quantitative sensory testing (°C), as well as suprathreshold tonic heat pain intensity (46.5 °C for 1 min) measured by 0–10 numerical pain scale (NPS) were obtained at a nonpainful site (thenar eminence) in all patients. Results No differences between the groups were found for gender, age, duration of pain, or duration of treatment (independent variables). No significant differences between the groups were found in punctuate (difference = 17.0 g (95% CI −8.8, 42.8), P = 0.19), pressure (2.2 mmHg (−28.7, 33.2), P = 0.89) and heat (−0.3 °C (−1.5, 0.9), P = 0.70) pain thresholds, or in suprathreshold heat pain intensity (difference between maximal pain intensities −0.4 NPS units (95% CI −1.2, 0.4), P = 0.31). Pearson correlations within the opioid-treated group failed to show significant relationships between any of the independent variables and the outcome measures. A further comparison of the outcomes between the ‘weak’ opioid-treated subgroup and the ‘strong’ opioid-treated subgroup again revealed insignificant results. Conclusions These results suggest that the administration of ‘commonly used’ dosages of oral opioids does not result in abnormal pain

  15. Oral opioid administration and hyperalgesia in patients with cancer or chronic nonmalignant pain.

    PubMed

    Reznikov, Igor; Pud, Dorit; Eisenberg, Elon

    2005-09-01

    Previous research has reported on reduced paw withdrawal latencies to heat and mechanical stimuli after parenteral administration of opioids in animals and on increased pain sensitivity in humans subsequent to postoperative infusions of short-acting opioids or in drug addicts. The aim of the present study was to explore the possibility that oral opioid treated patients with cancer-related or chronic nonmalignant pain differ in their pain sensitivity from patients treated with non-opioid analgesics. The study population consisted of 224 patients, including 142 in the opioid-treated group and 82 in the non-opioid-treated group. Pain thresholds for punctuate measured by von Frey filaments (g), mechanical pressure measured by pressure algometer (mmHg), heat stimuli measured by quantitative sensory testing (degrees C), as well as suprathreshold tonic heat pain intensity (46.5 degrees C for 1 min) measured by 0-10 numerical pain scale (NPS) were obtained at a nonpainful site (thenar eminence) in all patients. No differences between the groups were found for gender, age, duration of pain, or duration of treatment (independent variables). No significant differences between the groups were found in punctuate (difference = 17.0 g (95% CI -8.8, 42.8), P = 0.19), pressure (2.2 mmHg (-28.7, 33.2), P = 0.89) and heat (-0.3 degrees C (-1.5, 0.9), P = 0.70) pain thresholds, or in suprathreshold heat pain intensity (difference between maximal pain intensities -0.4 NPS units (95% CI -1.2, 0.4), P = 0.31). Pearson correlations within the opioid-treated group failed to show significant relationships between any of the independent variables and the outcome measures. A further comparison of the outcomes between the 'weak' opioid-treated subgroup and the 'strong' opioid-treated subgroup again revealed insignificant results. These results suggest that the administration of 'commonly used' dosages of oral opioids does not result in abnormal pain sensitivity beyond that of patients

  16. Effects of Oral Administration of CrCl3 on the Contents of Ca, Mg, Mn, Fe, Cu, and Zn in the Liver, Kidney, and Heart of Chicken.

    PubMed

    Liu, Yanhan; Zhao, Xiaona; Zhang, Xiao; Zhao, Xuejun; Liu, Yongxia; Liu, Jianzhu

    2016-06-01

    This study aimed to investigate the effects of oral administration of trivalent chromium on the contents of Ca, Mg, Mn, Fe, Cu, and Zn in the heart, liver, and kidney. Different levels of 1/8, 1/4, and 1/2 LD50 (LD50 = 5000 mg/kg body mass) CrCl3 milligrams per kilogram body mass daily were added into the water to establish the chronic poisoning model. Ca, Mg, Mn, Fe, Cu, and Zn were detected with the flame atomic absorption spectrometry in the organs exposed 14, 28, and 42 days to CrCl3, respectively. Results showed that Cr was accumulated in the heart, liver, and kidney significantly (P < 0.05) with extended time and dose. The contents of Ca and Fe increased, whereas those of Mg, Mn, Cu, and Zn decreased in the heart, liver, and kidney of each treated group, which had a dose- and time-dependent relationship, but the contents of Mg and Zn in the heart took on a fluctuated change. These particular observations were different from those in the control group. In conclusion, the oral administration of CrCl3 could change the contents of Ca, Mg, Mn, Fe, Cu, and Zn in the heart, liver, and kidney, which may cause disorders in the absorption and metabolism of the metal elements of chickens.

  17. Formation of Epichlorohydrin, a Known Rodent Carcinogen, Following Oral Administration of 1,3-Dichloro-2-propanol in Rats

    PubMed Central

    2015-01-01

    The observed toxicity and carcinogenicity of 1,3-dichloro-2-propanol (DCP) in rodents is thought to be due to the formation of reactive metabolites, epichlorohydrin (ECH) and dichloroacetone (DCA). However, there is no direct evidence for the formation of these metabolites from exposure to DCP in rodents due to the challenges of measuring these reactive intermediates directly in vivo. The objective of this work was to investigate the metabolism of DCP to ECH and DCA in vivo by first developing a sensitive analytical method in a suitable biological matrix and analyzing samples from rats administered DCP. DCA reacted rapidly in vitro in rat blood, plasma, and liver homogenate, precluding its detection. Because ECH rapidly disappeared in liver homogenate, but was relatively long-lived in plasma and blood in vitro, blood was selected for analysis of this metabolite. Following a single oral dose of 50 mg/kg DCP in male or female Harlan Sprague–Dawley rats, ECH was detected in blood with a maximum concentration reached at ≤13.7 min. ECH was cleared rapidly with a half-life of ca. 33 and 48 min in males and females, respectively. Following a single oral dose of 25 mg/kg ECH in male and female rats, the elimination half-life of ECH was ca. 34 and 20 min, respectively; the oral bioavailability of ECH was low (males, 5.2%; females, 2.1%), suggesting extensive first pass metabolism of ECH following oral administration. The area under the concentration vs time curve for ECH following oral administration of DCP and intravenous administration of ECH was used to estimate the percent of the DCP dose converted to ECH in rats. On the basis of this analysis, we concluded that in male and female rats following oral administration of 50 mg/kg DCP, ≥1.26% or ≥1.78% of the administered dose was metabolized to ECH, respectively. PMID:25254956

  18. Combined administration of antibiotics and direct oral anticoagulants: a renewed indication for laboratory monitoring?

    PubMed

    Lippi, Giuseppe; Favaloro, Emmanuel J; Mattiuzzi, Camilla

    2014-10-01

    The recent development and marketing of novel direct oral anticoagulants (DOACs) represents a paradigm shift in the management of patients requiring long-term anticoagulation. The advantages of these compounds over traditional therapy with vitamin K antagonists include a reportedly lower risk of severe hemorrhages and the limited need for laboratory measurements. However, there are several scenarios in which testing should be applied. The potential for drug-to-drug interaction is one plausible but currently underrecognized indication for laboratory assessment of the anticoagulant effect of DOACs. In particular, substantial concern has been raised during Phase I studies regarding the potential interaction of these drugs with some antibiotics, especially those that interplay with permeability glycoprotein (P-gp) and cytochrome 3A4 (CYP3A4). A specific electronic search on clinical trials published so far confirms that clarithromycin and rifampicin significantly impair the bioavailability of dabigatran, whereas clarithromycin, erythromycin, fluconazole, and ketoconazole alter the metabolism of rivaroxaban in vivo. Because of their more recent development, no published data were found for apixaban and edoxaban, or for potential interactions of DOACs with other and widely used antibiotics. It is noteworthy, however, that an online resource based on Food and Drug Administration and social media information, reports several hemorrhagic and thrombotic events in patients simultaneously taking dabigatran and some commonly used antibiotics such as amoxicillin, cephalosporin, and metronidazole. According to these reports, the administration of antibiotics in patients undergoing therapy with DOACs would seem to require accurate evaluation as to whether dose adjustments (personalized or antibiotic class driven) of the anticoagulant drug may be advisable. This might be facilitated by direct laboratory assessments of their anticoagulant effect ex vivo. Thieme Medical Publishers

  19. Acute oral administration of low doses of methylphenidate targets calretinin neurons in the rat septal area

    PubMed Central

    García-Avilés, Álvaro; Albert-Gascó, Héctor; Arnal-Vicente, Isabel; Elhajj, Ebtisam; Sanjuan-Arias, Julio; Sanchez-Perez, Ana María; Olucha-Bordonau, Francisco

    2015-01-01

    Methylphenidate (MPD) is a commonly administered drug to treat children suffering from attention deficit hyperactivity disorder (ADHD). Alterations in septal driven hippocampal theta rhythm may underlie attention deficits observed in these patients. Amongst others, the septo-hippocampal connections have long been acknowledged to be important in preserving hippocampal function. Thus, we wanted to ascertain if MPD administration, which improves attention in patients, could affect septal areas connecting with hippocampus. We used low and orally administered MPD doses (1.3, 2.7 and 5 mg/Kg) to rats what mimics the dosage range in humans. In our model, we observed no effect when using 1.3 mg/Kg MPD; whereas 2.7 and 5 mg/Kg induced a significant increase in c-fos expression specifically in the medial septum (MS), an area intimately connected to the hippocampus. We analyzed dopaminergic areas such as nucleus accumbens and striatum, and found that only 5 mg/Kg induced c-fos levels increase. In these areas tyrosine hydroxylase correlated well with c-fos staining, whereas in the MS the sparse tyrosine hydroxylase fibers did not overlap with c-fos positive neurons. Double immunofluorescence of c-fos with neuronal markers in the septal area revealed that co-localization with choline acethyl transferase, parvalbumin, and calbindin with c-fos did not change with MPD treatment; whereas, calretinin and c-fos double labeled neurons increased after MPD administration. Altogether, these results suggest that low and acute doses of methylphenidate primary target specific populations of caltretinin medial septal neurons. PMID:25852493

  20. Aqueous and vitreous penetration of linezolid and levofloxacin after oral administration.

    PubMed

    George, Jomy M; Fiscella, Richard; Blair, Michael; Rodvold, Keith; Ulanski, Lawrence; Stokes, John; Blair, Norman; Pontiggia, Laura

    2010-12-01

    To evaluate the time course of drug concentrations achieved in aqueous (AQ), vitreous (V), and serum (S) compartments after oral administration of linezolid and levofloxacin. Randomized, clinical trial. Clinical practice. Sixteen patients (16 eyes) undergoing vitrectomy who had not had a prior pars plana vitrectomy in the study eye were randomly assigned to one of 4 groups. AQ, V, and S samples were obtained from all subjects after single concomitant doses of linezolid 600 mg and levofloxacin 750 mg between 1 and 12 h before the procedure: group A = 1-3 h; group B = 3-6 h; group C = 6-9 h; group D = 9-12 h. AQ, V, and S concentrations of linezolid and levofloxacin. Overall mean concentrations ± standard deviation (μg/mL) achieved by linezolid in AQ, V, and S compartments were 3.32 ± 2.06, 2.98 ± 1.87, and 7.91 ± 3.94, respectively. Overall mean concentrations ±standard deviation (μg/mL) achieved by levofloxacin in AQ, V, and S compartments were 2.19 ± 1.92, 1.95 ± 1.27, and 7.38 ± 3.47, respectively. Single concomitant doses of linezolid and levofloxacin achieved AQ and V concentrations above the minimum inhibitory concentration for 90% of common ocular gram-positive and gram-negative pathogens up to 12 h after administration. The combination of linezolid and levofloxacin represents a viable option for the prophylaxis and management of endophthalmitis.

  1. Optimal timing of oral fosfomycin administration for pre-prostate biopsy prophylaxis.

    PubMed

    Rhodes, Nathaniel J; Gardiner, Bradley J; Neely, Michael N; Grayson, M Lindsay; Ellis, Andrew G; Lawrentschuk, Nathan; Frauman, Albert G; Maxwell, Kelly M; Zembower, Teresa R; Scheetz, Marc H

    2015-07-01

    As the optimal administration time for fosfomycin peri-procedural prophylaxis is unclear, we sought to determine optimal administration times for fosfomycin peri-procedural prophylaxis. Plasma, peripheral zone and transition zone fosfomycin concentrations were obtained from 26 subjects undergoing transurethral resection of the prostate (TURP), following a single oral dose of 3 g of fosfomycin. Population pharmacokinetic modelling was completed with the Nonparametric Adaptive Grid (NPAG) algorithm (Pmetrics package for R), with a four-compartment model. Plasma and tissue concentrations were simulated during the first 24 h post-dose, comparing these with EUCAST susceptibility breakpoints for Escherichia coli, a common uropathogen. Non-compartmental-determined pharmacokinetic values in our population were similar to those reported in the package insert. Predicted plasma concentrations rapidly increased after the first hour, giving more than 90% population coverage for organisms with an MIC ≤4 mg/L over the first 12 h post-dose. Organisms with higher MICs fared much worse, with organisms at the EUCAST breakpoint being covered for <10% of the population at any time. Transitional zone prostate concentrations exceeded 4 mg/L for 90% of the population between hours 1 and 9. Peripheral zone prostate concentrations were much lower and only exceeded 4 mg/L for 70% of the population between hours 1 and 4. Until more precise plasma and tissue data are available, we recommend that fosfomycin prophylaxis be given 1-4 h prior to prostate biopsy. We do not recommend fosfomycin prophylaxis for subjects with known organisms with MICs >4 mg/L. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Preoperative oral carbohydrate administration to ASA III-IV patients undergoing elective cardiac surgery.

    PubMed

    Breuer, Jan-P; von Dossow, Vera; von Heymann, Christian; Griesbach, Markus; von Schickfus, Michael; Mackh, Elise; Hacker, Cornelia; Elgeti, Ulrike; Konertz, Wolfgang; Wernecke, Klaus-D; Spies, Claudia D

    2006-11-01

    In this study we investigated the effects of preoperative oral carbohydrate administration on postoperative insulin resistance (PIR), gastric fluid volume, preoperative discomfort, and variables of organ dysfunction in ASA physical status III-IV patients undergoing elective cardiac surgery, including those with noninsulin-dependent Type-2 diabetes mellitus. Before surgery, 188 patients were randomized to receive a clear 12.5% carbohydrate drink (CHO), flavored water (placebo), or to fast overnight (control). CHO and placebo were treated in double-blind format and received 800 mL of the corresponding beverage in the evening and 400 mL 2 h before surgery. Patients were monitored from induction of general anesthesia until 24 h postoperatively. Exogenous insulin requirements to control blood glucose levels administration before cardiac surgery does not affect PIR. Clear fluids reduce thirst and may be recommended as a safe procedure in ASA III-IV patients. Further research is indicated to investigate possible cardioprotective effects of preoperative CHO intake.

  3. Peritoneal clearances in hypertensive CAPD patients after oral administration of clonidine, enalapril, and nifedipine.

    PubMed

    Favazza, A; Motanaro, D; Messa, P; Antonucci, F; Gropuzzo, M; Mioni, G

    1992-01-01

    The authors investigated whether the reduction of arterial pressure, induced by the oral administration of clonidine (CLO), enalapril (EN), and nifedipine (NIF), has any effect on peritoneal transport rates. The study was performed in nine hypertensive patients undergoing continuous ambulatory peritoneal dialysis (CAPD). The patients were submitted to administration of CLO, EN, and NIF, each in randomized succession for two weeks, after withdrawal of any hypotensive therapy for eight days (washout period). The nine patients underwent a four-hour dwell exchange using a 2.27 g/dL glucose two-liter bag after washout and after each hypotensive period. The following parameters were analyzed: mean arterial pressure (MAP), performed in the sitting position; net ultrafiltration; effluent/initial dialysate glucose ratio (GL D/Do); peritoneal clearance of K, BUN, creatinine (Cr), phosphate, beta-2 microglobulin (beta 2), total proteins, and the ratio between beta 2 and Cr clearance. Moreover, residual renal Cr and beta 2 clearances were analyzed. The three drugs significantly reduced MAP at a similar rate. The peritoneal transport parameters after CLO were similar to the results in the washout period. On the contrary, after EN and NIF therapy, Cr and beta 2 clearances were significantly increased, and GL D/Do decreased in comparison to the washout period. The other peritoneal transport parameters after EN and NIF were similar to the washout period. Residual renal Cr and beta 2 clearances after the three drugs were similar to those in the washout. these data suggest that after two weeks of therapy with EN and NIF, glucose, Cr, and beta 2 peritoneal transports are influenced by these hypotensive drugs irrespective of the effect on the arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Effect of Oral Administration of Bromelain on Postoperative Discomfort After Third Molar Surgery.

    PubMed

    Ghensi, Paolo; Cucchi, Alessandro; Creminelli, Luca; Tomasi, Cristiano; Zavan, Barbara; Maiorana, Carlo

    2017-03-01

    The purpose of this prospective randomized controlled clinical trial was to evaluate the effect of oral administration of bromelain on discomfort after mandibular third molar surgery. Eighty-four consecutive patients requiring surgical removal of a single mandibular impacted third molar under local anesthesia were randomly assigned to receiving no drug (control group, Group A), postoperative 40 mg bromelain every 6 hours for 6 days (Group B), preoperative 4 mg dexamethasone sodium phosphate as a submucosal injection (Group C), and preoperative 4 mg dexamethasone sodium phosphate as a submucosal injection plus postoperative 40 mg bromelain every 6 hours for 6 days (Group D). Standardized surgical and analgesic protocols were adopted. Maximum interincisal distance and facial contours were measured at baseline and on postoperative days 2 and 7. Pain was measured objectively by counting the number of analgesic tablets required. Patient perception of the severity of symptoms was assessed with a follow-up questionnaire (PoSSe scale). On postoperative day 2, there was a statistically significant reduction in facial edema in both Groups C and D compared with the control group, but no statistically significant differences were observed between Group B and the control group. At evaluation on postoperative day 7, Group D showed a statistically significant reduction in postoperative swelling compared with the control group. The combined use of bromelain and dexamethasone (Group D) induced a statistically significant reduction in the total number of analgesic tablets taken after surgery compared with the control group. The treatment groups had a limited, nonsignificant effect on trismus when compared with the control group. Bromelain used singly showed moderate anti-inflammatory efficacy, reducing postoperative swelling, albeit not to any significant extent compared with no drug administration. The combined use of bromelain and dexamethasone sodium phosphate yielded

  5. Acceptability of Daily Use of Free Oral Pre-exposure Prophylaxis (PrEP) Among Transgender Women Sex Workers in Shenyang, China.

    PubMed

    Wang, Zixin; Lau, Joseph T F; Yang, Xueying; Cai, Yong; Gross, Danielle L; Ma, Tiecheng; Liu, Yan

    2017-12-01

    This study investigated the acceptability of daily use of free oral pre-exposure prophylaxis (PrEP) and associated factors among transgender women sex workers in Shenyang, China, following a briefing on PrEP. A total of 183 HIV negative or sero-status unknown participants completed the cross-sectional survey. The prevalence of acceptability of daily use of free oral PrEP was 61.2%. Adjusting for education level and monthly income, variables on negative attitudes toward PrEP (i.e., having concerns about the side-effects of PrEP) [Adjusted odds ratios (AOR): 0.26], perceived subjective norms (i.e., perceiving support from male partners to take PrEP) (AOR: 2.08), and perceived behavioral control (e.g., perceiving complete control over using PrEP) (AOR: 2.10-16.72) were significantly associated with acceptability of daily use of free oral PrEP. In addition, experiencing violence during sex work, perceived risk of contracting HIV from clients and probable anxiety were also significant. Future PrEP promotion campaigns should consider these factors.

  6. Oral administration of royal jelly restores tear secretion capacity in rat blink-suppressed dry eye model by modulating lacrimal gland function.

    PubMed

    Imada, Toshihiro; Nakamura, Shigeru; Kitamura, Naoki; Shibuya, Izumi; Tsubota, Kazuo

    2014-01-01

    Tears are secreted from the lacrimal gland (LG), a dysfunction in which induces dry eye, resulting in ocular discomfort and visual impairment. Honey bee products are used as a nutritional source in daily life and medicine; however, little is known about their effects on dry eye. The aim of the present study was to investigate the effects of honey bee products on tear secretion capacity in dry eye. We selected raw honey, propolis, royal jelly (RJ), pollen, or larva from commercially available honey bee products. Tear secretion capacity was evaluated following the oral administration of each honey bee product in a rat blink-suppressed dry eye model. Changes in tear secretion, LG ATP content, and LG mitochondrial levels were measured. RJ restored the tear secretion capacity and decrease in LG ATP content and mitochondrial levels to the largest extent. Royal jelly can be used as a preventative intervention for dry eye by managing tear secretion capacity in the LG.

  7. Oral administration of grape seed polyphenol extract restores memory deficits in chronic cerebral hypoperfusion rats.

    PubMed

    Chen, Chen; Zheng, Yake; Wu, Tianwen; Wu, Chuanjie; Cheng, Xuan

    2017-04-01

    Chronic cerebral hypoperfusion (CCH) has been recognized as an important cause of both vascular dementia and Alzheimer's disease (AD), the two most prominent neurodegenerative diseases causing memory impairment in the elderly. However, an effective therapy for CCH-induced memory impairment has not yet been established. Grape seed polyphenol extract (GSPE) has powerful antioxidant properties and protects neurons and glia during ischemic injury, but its potential use in the prevention of CCH-induced memory impairment has not yet been investigated. Here, CCH-related memory impairment was modeled in rats using permanent bilateral occlusion of the common carotid artery. A Morris water maze task was used to evaluate memory, the levels of acetylcholinesterase, choline acetyltransferase, acetylcholine were used to evaluate cholinergic function, and oxidative stress was assessed by measuring the enzyme activity of superoxide dismutase, glutathione peroxidase, malonic dialdehyde, and catalase. We found that oral administration of GSPE for 1 month can rescue memory deficits. We also found that GSPE restores cholinergic neuronal function and represses oxidative damage in the hippocampus of CCH rats. We propose that GSPE protects memory in CCH rats by reducing ischemia-induced oxidative stress and cholinergic dysfunction. These findings provide a novel application of GSPE in CCH-related memory impairments.

  8. Nontransmission of deoxynivalenol (vomitoxin) to milk following oral administration to dairy cows.

    PubMed

    Prelusky, D B; Trenholm, H L; Lawrence, G A; Scott, P M

    1984-10-01

    The absorption of deoxynivalenol (DON; vomitoxin), a trichothecene mycotoxin produced by Fusarium species, was studied in the dairy cow. Serum and milk DON levels were quantitated following a single oral dose of 920 mg DON to each of two lactating cows of similar weight. Maximum blood levels for the two animals following DON administration were 200 and 90 ng/ml serum, occurring at times 4.7 and 3.5 hr, respectively. By 24 hr after dosing only trace levels (less than 2 ng/ml) were still detectable. DON in its conjugated form accounted for 24-46% of the total levels present in serum. Free and conjugated DON were also present in cow's milk, but only extremely low amounts (less than 4 ng/ml) were detected. Detection of DON was carried out utilizing Sep-Pak C18 extraction cartridges for isolation, with additional purification of the sample achieved by passing the extract through a short charcoal/alumina column. The extract was then reacted with N-heptafluorobutyrylimidazole prior to quantitation of the resulting DON-tris-heptafluorobutyrate derivative by combined gas chromatography-quadrupole mass spectrometry, using multiple selected ion monitoring. Detection limits were as low as 1 ng/ml (1 ppb).

  9. Ovarian Toxicity in Female Rats after Oral Administration of Melamine or Melamine and Cyanuric Acid

    PubMed Central

    Sun, Jiarui; Zhang, Xinchen; Cao, Yinan; Zhao, Qiling; Bao, Endong; Lv, Yingjun

    2016-01-01

    Although the toxicity of melamine to the kidneys and testes is well known, few studies have investigated the effects of melamine on female reproductive organs. Therefore, this study explores the effects of oral administration melamine or melamine and cyanuric acid for 28 days on the ovaries of female rats. Rats that were exposed to the mixture exhibited reduced ovarian and uterine weights, a shorter estrous cycle, and reduced serum estrogen and progesterone levels compared to rats that were exposed to melamine and control rats. Furthermore, morphological analysis revealed pathological changes in the ovaries of rats exposed to melamine or the mixture, such as more atretic follicles and necrosis of oocytes and granulosa cells. TUNEL staining revealed that the exposed groups had a higher proportion of TUNEL-positive granulosa cells than the control group, and the mRNA expressions of SOD1, GPX1, GPX2, P450scc, 17β-HSD I, and 17β-HSD II were reduced in the exposure groups compared with the control group. These results indicated that exposure to melamine alone or to the melamine-cyanuric acid mixture could damage the ovaries in rats. PMID:26866683

  10. Effect of the oral administration homeopathic Arnica montana on mitochondrial oxidative stress.

    PubMed

    de Camargo, Ronaldo Antônio; da Costa, Ellen Dias; Catisti, Rosana

    2013-01-01

    To analyze the effect of homeopathic Arnica on mitochondrial oxidative stress induced by Ca(2+) plus inorganic phosphate and/or Fe(2+)-citrate-mediated lipid peroxidation through changes in oxygen consumption rates. Mitochondria were isolated by differential centrifugation from the livers of adult male Wistar rats which had been treated with Arnica montana 6cH, 12cH, 30cH or succussed 30% ethanol (control) for 21 days. In the presence of antimycin-A, electron transport chain inhibitor, as evidenced by antimycin-A insensitive O(2) consumption, Arnica inhibited lipid peroxidation of mitochondrial membranes. In oxidative stress conditions, in the presence of Ca(2+) and inorganic phosphate, animals receiving Arnica 30cH had a significant decrease in mitochondrial O(2) consumption compared to control animals. When administrated orally, Arnica 30cH protects against hepatic mitochondrial membrane permeabilization induced by Ca(2+) and/or Fe(2+)-citrate-mediated lipid peroxidation and fragmentation of proteins due to the attack by reactive oxygen species. Copyright © 2012 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  11. Intestinal disposition of quercetin and its phase-II metabolites after oral administration in healthy volunteers.

    PubMed

    Chalet, Clément; Rubbens, Jari; Tack, Jan; Duchateau, Guus S; Augustijns, Patrick

    2018-05-15

    Quercetin is one of the main dietary flavonoids and undergoes a substantial intestinal phase-II metabolism. Quercetin conjugates have been detected in plasma and in urine, but their presence in the small intestine has not been assessed. This study aimed to investigate the intestinal metabolism and metabolite excretion of quercetin by the human small intestinal wall after oral dosing. Six healthy volunteers were given a capsule of 500 mg of quercetin with 240 ml of water. Duodenal fluids were collected using the intraluminal sampling technique for 4 h and analysed by LC-MS/MS. Phase-II metabolites of quercetin were detected and quantified in aspirated intestinal fluids. Metabolites appeared almost immediately after administration, indicating an intestinal metabolism and apical excretion into the lumen. Quercetin-3'-O-glucuronide was found to be the main intestinal metabolite. Our results could not conclude on the enterohepatic recycling of quercetin or its metabolites, although several individual profiles showed distinctive peaks. This study highlights the intestinal metabolism and excretion of quercetin and its conjugates in humans and gives insights into the relevant concentrations which should be used to investigate potential food-drug interactions in vitro. © 2018 Royal Pharmaceutical Society.

  12. Oral administration of Lactobacillus plantarum HY7714 protects hairless mouse against ultraviolet B-induced photoaging.

    PubMed

    Kim, Hyun Mee; Lee, Dong Eun; Park, Soo Dong; Kim, Yong-Tae; Kim, Yu Jin; Jeong, Ji Woong; Jang, Sung Sik; Ahn, Young-Tae; Sim, Jae-Hun; Huh, Chul-Sung; Chung, Dae Kyun; Lee, Jung-Hee

    2014-11-28

    Ultraviolet (UV) irradiation alters multiple molecular pathways in the skin, thereby inducing skin damage, including photoaging. In recent years, probiotics have gained interest due to their beneficial effects on skin health, such as inhibiting atopic dermatitis and improving skin immunity or inflammation. However, little is known about the effects of probiotics on UVBinduced photoaging. In this study, we evaluated the effect of Lactobacillus plantarum HY7714 against UVB-induced photoaging in human dermal fibroblasts and hairless mice. The results showed that L. plantarum HY7714 treatment effectively rescued UVB-reduced procollagen expression through the inhibition of UVB-induced matrix metalloproteinase (MMP)-1 expression in human dermal fibroblasts. Data from a western blot showed that L. plantarum HY7714 inhibited the phosphorylation of Jun N-terminal kinase, thereby suppressing the UVB-induced phosphorylation and expression of c-Jun. Oral administration of L. plantarum HY7714 clearly inhibited the number, depth, and area of wrinkles in hairless mouse skin. Histological data showed that L. plantarum HY7714 significantly inhibited UVB-induced epidermal thickness in mice. Western blot and zymography data also revealed that L. plantarum HY7714 effectively inhibited MMP-13 expression as well as MMP-2 and -9 activities in dermal tissue. Collectively, these results provide further insight regarding the skin biological actions of L. plantarum HY7714, a potential skin anti-photoaging agent.

  13. Oral administration of acarbose ameliorates imiquimod-induced psoriasis-like dermatitis in a mouse model.

    PubMed

    Chen, Hsin-Hua; Chao, Ya-Hsuan; Chen, Der-Yuan; Yang, Deng-Ho; Chung, Ting-Wen; Li, Yi-Rong; Lin, Chi Chen

    2016-04-01

    Psoriasis is a chronic autoimmune disease of undefined etiology that involves dysregulated interplay between immune cells and keratinocytes. Acarbose was found to decrease inflammatory parameters in diabetic patients in addition to its anti-diabetic effects. Here, we report that imiquimod (IMQ)-induced epidermal hyperplasia and psoriasis like-inflammation were significantly inhibited by acarbose treatment. Real-time PCR showed that mRNA levels of the cytokines TNF-α, IL-6, IL-1β IL-17A, and IL-22 in skin were also decreased significantly by acarbose. In addition, we found that acarbose reduced infiltration of CD3(+) T cells and GR-1(+) neutrophils in lesional skin and also reduced the percentage of IL-17-producing CD4(+) T cells (Th17) and IL-17- and IL-22-producing γδ T cells in the spleen. In contrast, acarbose increased the frequency of IL-10-producing CD4(+) regulator Tr1 T cells in the spleen and small intestine. These results indicate that oral administration of acarbose can attenuate the severity of imiquimod-induced psoriasis with local and systemic anti-inflammatory and immune modulation effects, thus suggesting that acarbose is an effective therapeutic strategy for psoriasis regulation. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Absorption, Distribution, Metabolism and Excretion of 3-MCPD 1-Monopalmitate after Oral Administration in Rats.

    PubMed

    Gao, Boyan; Liu, Man; Huang, Guoren; Zhang, Zhongfei; Zhao, Yue; Wang, Thomas T Y; Zhang, Yaqiong; Liu, Jie; Yu, Liangli

    2017-03-29

    Fatty acid esters of monochloropropane 1,2-diol (3-MCPD) are processing-induced toxicants and have been detected in several food categories. This study investigated the absorption, distribution, metabolism, and excretion of 3-MCPD esters in Sprague-Dawley (SD) rats using 3-MCPD 1-monopalmitate as the probe compound. The kinetics of 3-MCPD 1-monopalmitate in plasma was investigated using SD rats, and the results indicated that 3-MCPD 1-monopalmitate was absorbed directly in vivo and metabolized. Its primary metabolites in the liver, kidney, testis, brain, plasma, and urine were tentatively identified and measured at 6, 12, 24, and 48 h after oral administration. Structures were proposed for eight metabolites. 3-MCPD 1-monopalmitate was converted to free 3-MCPD, which formed the phase II metabolites. All of the metabolites were chlorine-related chemical components; most of them existed in urine, reflecting the excretion pattern of 3-MCPD esters. Understanding the metabolism of 3-MCPD esters in vivo is critical for assessing their toxicities.

  15. Accuracy of dispersing tramadol capsules for oral administration in young children.

    PubMed

    Kluger, M; Penrose, S; Bjorksten, A R; Chalkiadis, G

    2016-11-01

    Tramadol is used in children aged <12 years for analgesia, particularly for those at risk of obstructive sleep apnoea undergoing adenotonsillectomy. The Australian Therapeutic Goods Administration have strongly recommended that oral tramadol drops (100 mg/ml) not be used in children <12 years because of the risk of inadvertent overdose. The total mass of drug in a 10 ml bottle is 1000 mg. The only alternative preparation available is a 50 mg capsule that requires dispersion of a capsule's contents should smaller doses be required. The accuracy of this preparation has not been assessed. Twenty surgical ward nurses were asked to prepare a 15 mg dose of tramadol from a 50 mg capsule. The dose was within ±5% of 15 mg in 13 cases (65%) and within ±10% in 19 cases (95%) (range 13.9-17.1 mg). Despite the dose variability of this method of preparing tramadol, we consider it sufficiently accurate for clinical use. We also consider it safe, as even at the highest dose prepared, the variability would be unlikely to contribute to clinically significant side-effects or toxicity. Moreover, the maximal dose that could be administered is limited to the size of the capsule (50 mg).

  16. Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration

    PubMed Central

    Sidenius, Ulrik; Heegaard, Niels H.

    2016-01-01

    Gluten promotes type 1 diabetes in nonobese diabetic (NOD) mice and likely also in humans. In NOD mice and in non-diabetes-prone mice, it induces inflammation in the pancreatic lymph nodes, suggesting that gluten can initiate inflammation locally. Further, gliadin fragments stimulate insulin secretion from beta cells directly. We hypothesized that gluten fragments may cross the intestinal barrier to be distributed to organs other than the gut. If present in pancreas, gliadin could interact directly with the immune system and the beta cells to initiate diabetes development. We orally and intravenously administered 33-mer and 19-mer gliadin peptide to NOD, BALB/c, and C57BL/6 mice and found that the peptides readily crossed the intestinal barrier in all strains. Several degradation products were found in the pancreas by mass spectroscopy. Notably, the exocrine pancreas incorporated large amounts of radioactive label shortly after administration of the peptides. The study demonstrates that, even in normal animals, large gliadin fragments can reach the pancreas. If applicable to humans, the increased gut permeability in prediabetes and type 1 diabetes patients could expose beta cells directly to gliadin fragments. Here they could initiate inflammation and induce beta cell stress and thus contribute to the development of type 1 diabetes. PMID:27795959

  17. Modification of pharmacokinetics of norfloxacin following oral administration of curcumin in rabbits

    PubMed Central

    Pavithra, B. H.; Jayakumar, K.

    2009-01-01

    Investigation was carried out in adult New Zealand white rabbits to study the influence of curcumin pre-treatment on pharmacokinetic disposition of norfloxacin following single oral administration. Sixteen rabbits were divided into two groups of eight each consisting of either sex. Animals in group-I were administered norfloxacin (100 mg/kg body weight p.o), while animals in group-II received similar dose of norfloxacin after pre-treatment with curcumin (60 mg/kg body weight per day, 3 days, p.o). Blood samples were drawn from the marginal ear vein into heparin-coated vials at 0 (zero time), 5, 10, 15, 30 min and 1, 2, 4, 6, 12 and 24 h post-treatment. Plasma norfloxacin concentrations were determined by high performance liquid chromatography. The plasma concentration-time profile of norfloxacin was adequately described by a one-compartment open model. The pharmacokinetic data revealed that curcumin-treated animals had significantly (p ≤ 0.05) higher area under the plasma concentration-time curve and area under the first moment of plasma drug concentration-time curve. Prior treatment of curcumin significantly (p ≤ 0.05) increased elimination half-life and volume of distribution of norfloxacin. Further treatment with curcumin reduced loading and maintenance doses by 26% and 24% respectively. PMID:19934593

  18. EPA Announces the Availability of the Removal Administrative Record for the American Drum and Pallet Site in Memphis, Shelby County, Tennessee, the Daily News - Memphis, TN

    EPA Pesticide Factsheets

    Contains proof of publication of announcement of availability of the removal administrative record for the American Drum and Pallet Site in Memphis, Shelby County, Tennessee, in the Daily News newspaper Region ID: 04 DocID: 10547927, DocDate: 12-24-2007

  19. [Basic studies on oral administration of lentinan (I)--influence on lymphocyte subsets in peripheral venous blood].

    PubMed

    Hanaue, H; Tokuda, Y; Machimura, T; Tsukui, M; Mizutani, K; Huang, C M; Kamijoh, A; Kondo, Y; Ogoshi, K; Makuuchi, H

    1989-08-20

    The effect of oral administration of lentinan (LTN), a biological response modifier, in the control of systemic immune function was studied in 6-week old male Wistar-Imamichi SPF rats. In the LTN group, 1 mg LTN dissolved in 1 ml physiological saline was administration forcibly into the stomach twice weekly. Physiological saline alone was administered in a similar fashion to the control group. Blood samples were obtained prior to and after four and eight weeks of administration. White blood cells and lymphocyte counts were obtained and lymphocyte subsets were measured using monoclonal antibodies W3/13, W3/25 and 0 X 8 (Sera-Lab), and a laser flow cytometry system (Orthospectrum III, Orthodiagnostic System). The T cell ratio, helper/inducer T (Th) cell ratio, and suppressor/cytotoxic T (Ts) cell ratio were measured. The peripheral white blood cell count and lymphocyte count were not significantly different between the control and LTN groups. After four weeks of LTN administration, however, the LTN group showed a significantly higher T cell ratio, Th cell ratio and Th/Ts cell ratio than did the control group, and the Ts cell ratio was significantly lower. In the groups undergoing administration for eight weeks, no difference was noted in the lymphocyte subsets between the two groups. Oral administration of LTN apparently modulates the systemic immune function through T cell stimulation, especially Th cells, but continued administration may induce a tolerance to the effect of LTN.

  20. Administrative Challenges to the Integration of Oral Health With Primary Care: A SWOT Analysis of Health Care Executives at Federally Qualified Health Centers.

    PubMed

    Norwood, Connor W; Maxey, Hannah L; Randolph, Courtney; Gano, Laura; Kochhar, Komal

    Inadequate access to preventive oral health services contributes to oral health disparities and is a major public health concern in the United States. Federally Qualified Health Centers play a critical role in improving access to care for populations affected by oral health disparities but face a number of administrative challenges associated with implementation of oral health integration models. We conducted a SWOT (strengths, weaknesses, opportunities, and threats) analysis with health care executives to identify strengths, weaknesses, opportunities, and threats of successful oral health integration in Federally Qualified Health Centers. Four themes were identified: (1) culture of health care organizations; (2) operations and administration; (3) finance; and (4) workforce.

  1. Oral administration of eicosapentaenoic acid or docosahexaenoic acid modifies cardiac function and ameliorates congestive heart failure in male rats.

    PubMed

    Yamanushi, Tomoko T; Kabuto, Hideaki; Hirakawa, Eiichiro; Janjua, Najma; Takayama, Fusako; Mankura, Mitsumasa

    2014-04-01

    This study assessed the effects of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on normal cardiac function (part 1) and congestive heart failure (CHF) (part 2) through electrocardiogram analysis and determination of EPA, DHA, and arachidonic acid (AA) concentrations in rat hearts. In part 2, pathologic assessments were also performed. For part 1 of this study, 4-wk-old male rats were divided into a control group and 2 experimental groups. The rats daily were orally administered (1 g/kg body weight) saline, EPA-ethyl ester (EPA-Et; E group), or DHA-ethyl ester (DHA-Et; D group), respectively, for 28 d. ECGs revealed that QT intervals were significantly shorter for groups E and D compared with the control group (P ≤ 0.05). Relative to the control group, the concentration of EPA was higher in the E group and concentrations of EPA and DHA were higher in the D group, although AA concentrations were lower (P ≤ 0.05). In part 2, CHF was produced by subcutaneous injection of monocrotaline into 5-wk-old rats. At 3 d before monocrotaline injection, rats were administered either saline, EPA-Et, or DHA-Et as mentioned above and then killed at 21 d. The study groups were as follows: normal + saline (control), CHF + saline (H group), CHF + EPA-Et (HE group), and CHF + DHA-Et (HD group). QT intervals were significantly shorter (P ≤ 0.05) in the control and HD groups compared with the H and HE groups. Relative to the H group, concentrations of EPA were higher in the HE group and those of DHA were higher in the control and HD groups (P ≤ 0.05). There was less mononuclear cell infiltration in the myocytes of the HD group than in the H group (P = 0.06). The right ventricles in the H, HE, and HD groups showed significantly increased weights (P ≤ 0.05) compared with controls. The administration of EPA-Et or DHA-Et may affect cardiac function by modification of heart fatty acid composition, and the administration of DHA-Et may ameliorate CHF.

  2. Toxicity evaluation of methoxy poly(ethylene oxide)-block-poly(ε-caprolactone) polymeric micelles following multiple oral and intraperitoneal administration to rats.

    PubMed

    Binkhathlan, Ziyad; Qamar, Wajhul; Ali, Raisuddin; Kfoury, Hala; Alghonaim, Mohammed

    2017-09-01

    Methoxy poly(ethylene oxide)- block -poly(ɛ-caprolactone) (PEO- b -PCL) copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO- b -PCL block copolymers and assess the toxic effects of drug-free PEO- b -PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip) administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO- b -PCL micelles, sixty animals were divided into two major groups: The first group received PEO- b -PCL micelles (100 mg/kg) by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen) were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

  3. Halloysite nanotubes-induced Al accumulation and oxidative damage in liver of mice after 30-day repeated oral administration.

    PubMed

    Wang, Xue; Gong, Jiachun; Gui, Zongxiang; Hu, Tingting; Xu, Xiaolong

    2018-06-01

    Halloysite (Al 2 Si 2 O 5 (OH) 4 ·nH 2 O) nanotubes (HNTs) are natural clay materials and widely applied in many fields due to their natural hollow tubular structures. Many in vitro studies indicate that HNTs exhibit a high level of biocompatibility, however the in vivo toxicity of HNTs remains unclear. The objective of this study was to assess the hepatic toxicity of the purified HNTs in mice via oral route. The purified HNTs were orally administered to mice at 5, 50, and 300 mg/kg body weight (BW) every day for 30 days. Oral administration of HNTs stimulated the growth of the mice at the low dose (5 mg/kg BW) with no liver toxicity, but inhibited the growth of the mice at the middle (50 mg/kg BW) and high (300 mg/kg BW) doses. In addition, oral administration of HNTs at the high dose caused Al accumulation in the liver but had no marked effect on the Si content in the organ. The Al accumulation caused significant oxidative stress in the liver, which induced hepatic dysfunction and histopathologic changes. These findings demonstrated that Al accumulation-induced oxidative stress played an important role in the oral HNTs-caused liver injury. © 2018 Wiley Periodicals, Inc.

  4. Oral administration of D-aspartate, but not L-aspartate, depresses rectal temperature and alters plasma metabolites in chicks.

    PubMed

    Erwan, Edi; Chowdhury, Vishwajit Sur; Nagasawa, Mao; Goda, Ryosei; Otsuka, Tsuyoshi; Yasuo, Shinobu; Furuse, Mitsuhiro

    2014-07-25

    L-Aspartate (L-Asp) and D-aspartate (D-Asp) are physiologically important amino acids in mammals and birds. However, the functions of these amino acids have not yet been fully understood. In this study, we therefore examined the effects of L-Asp and D-Asp in terms of regulating body temperature, plasma metabolites and catecholamines in chicks. Chicks were first orally administered with different doses (0, 3.75, 7.5 and 15 mmol/kg body weight) of L- or D-Asp to monitor the effects of these amino acids on rectal temperature during 120 min of the experimental period. Oral administration of D-Asp, but not of L-Asp, linearly decreased the rectal temperature in chicks. Importantly, orally administered D-Asp led to a significant reduction in body temperature in chicks even under high ambient temperature (HT) conditions. However, centrally administered D-Asp did not significantly influence the body temperature in chicks. As for plasma metabolites and catecholamines, orally administered D-Asp led to decreased triacylglycerol and uric acid concentrations and increased glucose and chlorine concentrations but did not alter plasma catecholamines. These results suggest that oral administration of D-Asp may play a potent role in reducing body temperature under both normal and HT conditions. The alteration of plasma metabolites further indicates that D-Asp may contribute to the regulation of metabolic activity in chicks. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. The pharmacokinetics of methocarbamol and guaifenesin after single intravenous and multiple-dose oral administration of methocarbamol in the horse.

    PubMed

    Rumpler, M J; Colahan, P; Sams, R A

    2014-02-01

    A simple LC/MSMS method has been developed and fully validated to determine concentrations and characterize the concentration vs. time course of methocarbamol (MCBL) and guaifenesin (GGE) in plasma after a single intravenous dose and multiple oral dose administrations of MCBL to conditioned Thoroughbred horses. The plasma concentration-time profiles for MCBL after a single intravenous dose of 15 mg/kg of MCBL were best described by a three-compartment model. Mean extrapolated peak (C0 ) plasma concentrations were 23.2 (± 5.93) μg/mL. Terminal half-life, volume of distribution at steady-state, mean residence time, and systemic clearance were characterized by a median (range) of 2.96 (2.46-4.71) h, 1.05 (0.943-1.21) L/kg, 1.98 (1.45-2.51) h, and 8.99 (6.68-10.8) mL/min/kg, respectively. Oral dose of MCBL was characterized by a median (range) terminal half-life, mean transit time, mean absorption time, and apparent oral clearance of 2.89 (2.21-4.88) h, 2.67 (1.80-2.87) h, 0.410 (0.350-0.770) h, and 16.5 (13.0-20) mL/min/kg. Bioavailability of orally administered MCBL was characterized by a median (range) of 54.4 (43.2-72.8)%. Guaifenesin plasma concentrations were below the limit of detection in all samples collected after the single intravenous dose of MCBL whereas they were detected for up to 24 h after the last dose of the multiple-dose oral regimen. This difference may be attributed to first-pass metabolism of MCBL to GGE after oral administration and may provide a means of differentiating the two routes of administration. © 2013 John Wiley & Sons Ltd.

  6. [Pharmacokinetics after oral and intravenous administration of d,l-monolysine acetylsalicylate and an oral dose of acetylsalicylic acid in healthy volunteers].

    PubMed

    Raschka, C; Koch, H J

    2001-01-01

    We studied the ASA pharmacokinetics of single doses of 500 mg and 1000 mg of D,L-lysine-monoacetylsalicylate (Lys-ASA) administered both orally (Delgesic) and 500 mg parenterally (Aspisol) as well as 500 mg acetylsalicylate (ASA, Aspirin) in 13 healthy volunteers. Blood samples were taken before and at defined times up to 48 h after application of Lys-ASA and ASA. Analysis for ASA and its metabolite salicylic acid were performed by HPLC. All concentration versus time data were presented descriptively. As far as ASA was concerned, differences were assessed by means of ANOVA according to Friedman including post hoc Wilcoxon tests for each time point. Pharmacokinetic parameters were calculated based on a one-compartment model. The concentration vs. time curves after oral intake of 500 mg of ASA and Lys-ASA differed significantly (p < 0.001). Peak serum ASA concentrations (Cmax) were 6.8 mg/l for oral Lys-ASA and 2.7 mg/l for ASA per os. The corresponding tmax-values were 14.2 and 38.0 min. Absolute bioavailabilities for 500 mg doses were 75.4 and 63.4 pour cent, respectively. After intake of 100 mg and 1000 mg oral doses of Lys-ASA Cmax was 2.7 mg/l and 15.9 mg/l, tmax being 14.2 min for the 1000 mg dose. The shortest half-life was found after i.v. injection with 7.5 min. Metabolism was fast with maximum rise of salicylic acid concentration after injection of Lys-ASS. We conclude that concerning time dimension oral administration of Lys-ASA is almost equivalent to i.v. Lys-ASA and may be an alternative for i.v. administration in cases of acute heart attacks.

  7. Intestinal microbiota and oral administration of Enterococcus faecium associated with the growth performance of new-born piglets.

    PubMed

    Wang, Y B; Du, W; Fu, A K; Zhang, X P; Huang, Y; Lee, K H; Yu, K; Li, W F; Li, Y L

    2016-09-01

    The oral administration of Enterococcus faecium EF1 to new-born suckling and weaning piglets along with their growth performances and intestinal microbiota was investigated in this study. Twenty-four new-born piglets were initially divided into 2 groups. The probiotics group received 2 ml of 10% sterilised skimmed milk by oral gavage supplemented with 6×10(8) cfu/ml viable E. faecium EF1 at the first, the third and the fifth day after birth, while the control group received 2 ml of 10% sterilised skimmed milk without probiotics at the same time. Results showed that oral administration of E. faecium EF1 was associated with a remarkable increase on the body weight of piglets for both suckling and weaning periods, by 30.73% (P<0.01) and 320.84% (P<0.01), and also decreased the diarrhoea rate, by 43.21% (P<0.05) and 71.42% (P<0.05), respectively. In addition, 454-pyrosequencing analysis revealed that there was no significant difference in the intestinal microbial diversity of the suckling piglets between the two groups; nevertheless, when compared to the control group, the relative abundance of Firmicutes in the probiotics group was substantially augmented, while the relative abundance of Proteobacteria, Bacteroidetes and Fusobacteria diminished. However, results indicated that oral administration of E. faecium EF1 did not have any influence on the relative abundance of Firmicutes in weaning piglets rather than increasing the relative abundance of Bacteroidetes and decreasing the relative abundance of Proteobacteria. Furthermore, at the level of the Firmicutes phylum, the relative abundance of Lactobacillales in the probiotic group increased significantly. These findings suggest that oral administration of E. faecium EF1 to new-born piglets could improve the growth performance and intestinal microbiota of piglets for both suckling and weaning periods.

  8. Oral administration of glucosylceramide ameliorates inflammatory dry-skin condition in chronic oxazolone-induced irritant contact dermatitis in the mouse ear.

    PubMed

    Yeom, Mijung; Kim, Sung-Hun; Lee, Bombi; Han, Jeong-Jun; Chung, Guk Hoon; Choi, Hee-Don; Lee, Hyejung; Hahm, Dae-Hyun

    2012-08-01

    Irritant contact dermatitis (ICD) is an inflammatory skin disease triggered by exposure to a chemical that is toxic or irritating to the skin. A major characteristic of chronic ICD is an inflammatory dry-skin condition with associated itching. Although glucosylceramide (GlcCer) is known to improve the skin barrier function, its mechanism of action is unknown. Using a mouse model of oxazolone-induced chronic ICD, this study investigated the effects of oral administration of GlcCer on inflammatory dry skin. Chronic ICD was induced by repeated application of oxazolone in mice. GlcCer was orally administered once daily throughout the elicitation phase. The beneficial efficacy of GlcCer on cutaneous inflammation was evaluated by assessing ear thickness, lymph node weight, histological findings, and mRNA expression of pro-inflammatory cytokines such as IL-1β and IL-6. Additionally, parameters of the itch-associated response, including scratching behavior, water content of the skin, and aquaporin-3 levels in the lesional ear, were measured. Oral GlcCer administration significantly suppressed mRNA expression of the pro-inflammatory cytokines IL-1β and IL-6. GlcCer also suppressed ear swelling, lymph node weight gains, and infiltration of leukocytes and mast cells in ICD mice. In oxazolone-induced ICD mice, GlcCer significantly inhibited irritant-related scratching behavior and dehydration of the stratum corneum, and decreased aquaporin-3 expression. Our results indicate that GlcCer suppressed inflammation not only by inhibiting cytokine production but also by repairing the skin barrier function, suggesting a potential beneficial role for GlcCer in the improvement of chronic ICD. Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  9. Oral administration of arginine enhances the growth hormone response to growth hormone releasing hormone in short children.

    PubMed

    Loche, S; Carta, D; Muntoni, A C; Corda, R; Pintor, C

    1993-10-01

    We have evaluated the effect of oral administration of arginine chlorhydrate on the growth hormone response to growth hormone releasing hormone in a group of nine short prepubertal children (six boys and four girls). Arginine chlorhydrate 10 g, administered orally 60 min before an i.v. bolus injection of growth hormone releasing hormone 1-29, 1 microgram/kg, significantly enhanced the growth hormone response to the neuropeptide, confirming the results of previous studies which used the i.v. route. Furthermore, our data strengthen the view that the effects of arginine chlorhydrate on growth hormone secretion are mediated by inhibition of endogenous somatostatin release.

  10. Lack of dose dependent kinetics of methyl salicylate-2-O-β-D-lactoside in rhesus monkeys after oral administration.

    PubMed

    He, Yangyang; Yan, Yu; Zhang, Tiantai; Ma, Yinzhong; Zhang, Wen; Wu, Ping; Song, Junke; Wang, Shuang; Du, Guanhua

    2015-04-22

    Methyl salicylate-2-O-β-d-lactoside (MSL) is one of the main active components isolated from Gaultheria yunnanensis, which is a traditional Chinese medicine used to treat arthritis and various aches and pains. Pharmacological researches showed that MSL had various effective activities in both in vivo and in vitro experiments. However, the pharmacokinetics features and oral bioavailability of MSL in primates were not studied up to now. To study the pharmacokinetics of different doses of MSL in rhesus monkeys and investigate the absolute bioavailability of MSL after oral administration. Male and female rhesus monkeys were either orally administrated with MSL 200, 400 and 800 mg/kg or received an intravenous dose of 20mg/kg randomly. The levels of MSL and salicylic acid (SA) in plasma were simultaneous measured by a simple, sensitive and reproducible high performance liquid chromatography method. Mean peak plasma concentration values for groups treated with 200, 400 and 800 mg/kg doses ranged from 48.79 to 171.83 μg/mL after single-dose oral administration of MSL, and mean area under the concentration-time curve values ranged from 195.16 to 1107.76 μg/mL h. Poor linearity of the kinetics of SA after oral administration of MSL was observed in the regression analysis of the Cmax-dose plot (r(2)=0.812), CL-dose plot (r(2)=0.225) and AUC(0-t)-dose plot (r(2)=0.938). Absolute bioavailability of MSL was assessed to be 118.89 ± 57.50, 213.54 ± 58.98 and 168.72 ± 76.58%, respectively. Bioavailability of MSL after oral administration in rhesus monkeys was measured for the first time. Pharmacokinetics parameters did not appear to be dose proportional among the three oral doses of treatments, and MSL showed an apparent absolute bioavailability in excess of 100% in rhesus monkeys based on the present study. In addition, a rapid, sensitive and reliable HPLC method was established and demonstrated for the research of traditional Chinese medicine in this study. Copyright

  11. The macrocyclic tetrapeptide [D-Trp]CJ-15,208 produces short-acting κ opioid receptor antagonism in the CNS after oral administration

    PubMed Central

    Eans, Shainnel O; Ganno, Michelle L; Reilley, Kate J; Patkar, Kshitij A; Senadheera, Sanjeewa N; Aldrich, Jane V; McLaughlin, Jay P

    2013-01-01

    Background and Purpose Cyclic peptides are resistant to proteolytic cleavage, therefore potentially exhibiting activity after systemic administration. We hypothesized that the macrocyclic κ opioid receptor (KOR)-selective antagonist [D-Trp]CJ-15,208 would demonstrate antagonist activity after systemic, that is, s.c. and oral (per os, p. o.), administration. Experimental Approach C57BL/6J mice were pretreated with [D-Trp]CJ-15,208 s.c. or p.o. before administration of the KOR-selective agonist U50,488 and the determination of antinociception in the warm-water tail-withdrawal assay. The locomotor activity of mice treated with [D-Trp]CJ-15,208 was determined by rotorod testing. Additional mice demonstrating cocaine conditioned place preference and subsequent extinction were pretreated daily with vehicle or [D-Trp]CJ-15,208 and then exposed to repeated forced swim stress or a single additional session of cocaine place conditioning before redetermining place preference. Key Results Pretreatment with [D-Trp]CJ-15,208 administered s.c. or p.o. dose-dependently antagonized the antinociception induced by i.p. administration of U50,488 in mice tested in the warm-water tail-withdrawal assay for less than 12 and 6 h respectively. [D-Trp]CJ-15,208 also produced limited (<25%), short-duration antinociception mediated through KOR agonism. Orally administered [D-Trp]CJ-15,208 dose-dependently antagonized centrally administered U50,488-induced antinociception, and prevented stress-, but not cocaine-induced, reinstatement of extinguished cocaine-seeking behaviour, consistent with its KOR antagonist activity, without affecting locomotor activity. Conclusions and Implications The macrocyclic tetrapeptide [D-Trp]CJ-15,208 is a short-duration KOR antagonist with weak KOR agonist activity that is active after oral administration and demonstrates blood–brain barrier permeability. These data validate the use of systemically active peptides such as [D-Trp]CJ-15,208 as potentially useful

  12. The macrocyclic tetrapeptide [D-Trp]CJ-15,208 produces short-acting κ opioid receptor antagonism in the CNS after oral administration.

    PubMed

    Eans, Shainnel O; Ganno, Michelle L; Reilley, Kate J; Patkar, Kshitij A; Senadheera, Sanjeewa N; Aldrich, Jane V; McLaughlin, Jay P

    2013-05-01

    Cyclic peptides are resistant to proteolytic cleavage, therefore potentially exhibiting activity after systemic administration. We hypothesized that the macrocyclic κ opioid receptor (KOR)-selective antagonist [D-Trp]CJ-15,208 would demonstrate antagonist activity after systemic, that is, s.c. and oral (per os, p. o.), administration. C57BL/6J mice were pretreated with [D-Trp]CJ-15,208 s.c. or p.o. before administration of the KOR-selective agonist U50,488 and the determination of antinociception in the warm-water tail-withdrawal assay. The locomotor activity of mice treated with [D-Trp]CJ-15,208 was determined by rotorod testing. Additional mice demonstrating cocaine conditioned place preference and subsequent extinction were pretreated daily with vehicle or [D-Trp]CJ-15,208 and then exposed to repeated forced swim stress or a single additional session of cocaine place conditioning before redetermining place preference. Pretreatment with [D-Trp]CJ-15,208 administered s.c. or p.o. dose-dependently antagonized the antinociception induced by i.p. administration of U50,488 in mice tested in the warm-water tail-withdrawal assay for less than 12 and 6 h respectively. [D-Trp]CJ-15,208 also produced limited (<25%), short-duration antinociception mediated through KOR agonism. Orally administered [D-Trp]CJ-15,208 dose-dependently antagonized centrally administered U50,488-induced antinociception, and prevented stress-, but not cocaine-induced, reinstatement of extinguished cocaine-seeking behaviour, consistent with its KOR antagonist activity, without affecting locomotor activity. The macrocyclic tetrapeptide [D-Trp]CJ-15,208 is a short-duration KOR antagonist with weak KOR agonist activity that is active after oral administration and demonstrates blood-brain barrier permeability. These data validate the use of systemically active peptides such as [D-Trp]CJ-15,208 as potentially useful therapeutics. © 2013 The Authors. British Journal of Pharmacology © 2013 The

  13. A Comparison of Betamethasone Valerate 0.1% Cream Twice Daily Plus Oral Simvastatin Versus Betamethasone Valerate 0.1% Cream Alone in the Treatment of Vitiligo Patients.

    PubMed

    Iraji, Fariba; Banihashemi, Seyed Hossin; Faghihi, Gita; Shahmoradi, Zabihollah; Tajmirriahi, Nabet; Jazi, Safoura Bokaie

    2017-01-01

    Vitiligo, a common disorder of depigmentation, is often difficult to treat. Corticosteroids are known to be effective, but with modest results. Although simvastatin has been reported to be effective for immunorelated dermatologic disorders including vitiligo, controlled trials are lacking. This study was conducted to compare the efficacy of topical betamethasone valerate 0.1% cream (as a standard method of treatment for vitiligo) versus a combination of betamethasone valerate plus oral simvastatin in the treatment of vitiligo. Eighty-eight subjects with symmetric vitiligo who had body surface involvement up to 20% were divided randomly into two groups. Group A were treated with betamethasone valerate 01% cream twice daily and Group B with betamethasone valerate 01% cream twice daily and oral simvastatin 80 mg daily for 12 weeks. Finally, 46 patients completed treatment after 12 weeks in both groups. The results were evaluated by a blind dermatologist using Vitiligo Area Scoring Index (VASI) score at baseline, 4 th , 8 th , and 12 th week of treatment. In a similar way, subjective assessment performed by patients based on photo evaluation at the end of the study. Despite a continuous reduction in VASI score in both groups, according to both physician ( P = 0.13) and patient ( P = 0.374) assessment oral simvastatin was not statistically more effective than conventional treatment of vitiligo. This study indicates that oral simvastatin is not associated with significant impacts in the treatment of vitiligo as compared to other inflammatory dermatologic conditions such as psoriasis. Indeed, other studies should be initiated regarding exact molecular and cellular effects of statins in the treatment of vitiligo.

  14. A Comparison of Betamethasone Valerate 0.1% Cream Twice Daily Plus Oral Simvastatin Versus Betamethasone Valerate 0.1% Cream Alone in the Treatment of Vitiligo Patients

    PubMed Central

    Iraji, Fariba; Banihashemi, Seyed Hossin; Faghihi, Gita; Shahmoradi, Zabihollah; Tajmirriahi, Nabet; Jazi, Safoura Bokaie

    2017-01-01

    Background: Vitiligo, a common disorder of depigmentation, is often difficult to treat. Corticosteroids are known to be effective, but with modest results. Although simvastatin has been reported to be effective for immunorelated dermatologic disorders including vitiligo, controlled trials are lacking. This study was conducted to compare the efficacy of topical betamethasone valerate 0.1% cream (as a standard method of treatment for vitiligo) versus a combination of betamethasone valerate plus oral simvastatin in the treatment of vitiligo. Materials and Methods: Eighty-eight subjects with symmetric vitiligo who had body surface involvement up to 20% were divided randomly into two groups. Group A were treated with betamethasone valerate 01% cream twice daily and Group B with betamethasone valerate 01% cream twice daily and oral simvastatin 80 mg daily for 12 weeks. Finally, 46 patients completed treatment after 12 weeks in both groups. The results were evaluated by a blind dermatologist using Vitiligo Area Scoring Index (VASI) score at baseline, 4th, 8th, and 12th week of treatment. In a similar way, subjective assessment performed by patients based on photo evaluation at the end of the study. Results: Despite a continuous reduction in VASI score in both groups, according to both physician (P = 0.13) and patient (P = 0.374) assessment oral simvastatin was not statistically more effective than conventional treatment of vitiligo. Conclusion: This study indicates that oral simvastatin is not associated with significant impacts in the treatment of vitiligo as compared to other inflammatory dermatologic conditions such as psoriasis. Indeed, other studies should be initiated regarding exact molecular and cellular effects of statins in the treatment of vitiligo. PMID:28516068

  15. Predictive model accuracy in estimating last Δ9-tetrahydrocannabinol (THC) intake from plasma and whole blood cannabinoid concentrations in chronic, daily cannabis smokers administered subchronic oral THC.

    PubMed

    Karschner, Erin L; Schwope, David M; Schwilke, Eugene W; Goodwin, Robert S; Kelly, Deanna L; Gorelick, David A; Huestis, Marilyn A

    2012-10-01

    Determining time since last cannabis/Δ9-tetrahydrocannabinol (THC) exposure is important in clinical, workplace, and forensic settings. Mathematical models calculating time of last exposure from whole blood concentrations typically employ a theoretical 0.5 whole blood-to-plasma (WB/P) ratio. No studies previously evaluated predictive models utilizing empirically-derived WB/P ratios, or whole blood cannabinoid pharmacokinetics after subchronic THC dosing. Ten male chronic, daily cannabis smokers received escalating around-the-clock oral THC (40-120 mg daily) for 8 days. Cannabinoids were quantified in whole blood and plasma by two-dimensional gas chromatography-mass spectrometry. Maximum whole blood THC occurred 3.0 h after the first oral THC dose and 103.5h (4.3 days) during multiple THC dosing. Median WB/P ratios were THC 0.63 (n=196), 11-hydroxy-THC 0.60 (n=189), and 11-nor-9-carboxy-THC (THCCOOH) 0.55 (n=200). Predictive models utilizing these WB/P ratios accurately estimated last cannabis exposure in 96% and 100% of specimens collected within 1-5h after a single oral THC dose and throughout multiple dosing, respectively. Models were only 60% and 12.5% accurate 12.5 and 22.5h after the last THC dose, respectively. Predictive models estimating time since last cannabis intake from whole blood and plasma cannabinoid concentrations were inaccurate during abstinence, but highly accurate during active THC dosing. THC redistribution from large cannabinoid body stores and high circulating THCCOOH concentrations create different pharmacokinetic profiles than those in less than daily cannabis smokers that were used to derive the models. Thus, the models do not accurately predict time of last THC intake in individuals consuming THC daily. Published by Elsevier Ireland Ltd.

  16. Predictive model accuracy in estimating last Δ9-tetrahydrocannabinol (THC) intake from plasma and whole blood cannabinoid concentrations in chronic, daily cannabis smokers administered subchronic oral THC*

    PubMed Central

    Karschner, Erin L.; Schwope, David M.; Schwilke, Eugene W.; Goodwin, Robert S.; Kelly, Deanna L.; Gorelick, David A.; Huestis, Marilyn A.

    2012-01-01

    Background Determining time since last cannabis/Δ9-tetrahydrocannabinol (THC) exposure is important in clinical, workplace, and forensic settings. Mathematical models calculating time of last exposure from whole blood concentrations typically employ a theoretical 0.5 whole blood-to-plasma (WB/P) ratio. No studies previously evaluated predictive models utilizing empirically-derived WB/P ratios, or whole blood cannabinoid pharmacokinetics after subchronic THC dosing. Methods Ten male chronic, daily cannabis smokers received escalating around-the-clock oral THC (40-120 mg daily) for 8 days. Cannabinoids were quantified in whole blood and plasma by two-dimensional gas chromatography-mass spectrometry. Results Maximum whole blood THC occurred 3.0 h after the first oral THC dose and 103.5 h (4.3 days) during multiple THC dosing. Median WB/P ratios were THC 0.63 (n=196), 11-hydroxy-THC 0.60 (n=189), and 11-nor-9-carboxy-THC (THCCOOH) 0.55 (n=200). Predictive models utilizing these WB/P ratios accurately estimated last cannabis exposure in 96% and 100% of specimens collected within 1-5 h after a single oral THC dose and throughout multiple dosing, respectively. Models were only 60% and 12.5% accurate 12.5 and 22.5 h after the last THC dose, respectively. Conclusions Predictive models estimating time since last cannabis intake from whole blood and plasma cannabinoid concentrations were inaccurate during abstinence, but highly accurate during active THC dosing. THC redistribution from large cannabinoid body stores and high circulating THCCOOH concentrations create different pharmacokinetic profiles than those in less than daily cannabis smokers that were used to derive the models. Thus, the models do not accurately predict time of last THC intake in individuals consuming THC daily. PMID:22464363

  17. [Evaluation of combination chemotherapy with oral S-1 administration followed by docetaxel by superselective intra-arterial infusion for patients with oral squamous cell carcinomas].

    PubMed

    Nagai, Hirokazu; Takamaru, Natsumi; Ohe, Go; Uchida, Daisuke; Tamatani, Tetsuya; Fujisawa, Kenji; Iwamoto, Seiji; Miyamoto, Youji

    2011-05-01

    The purpose of this study was to evaluate the effectiveness and adverse events of combination chemotherapy with oral S-1 administration following docetaxel (DOC) treatment by superselective intra-arterial infusion as neo-adjuvant chemotherapy (NAC) for patients with oral squamous cell carcinoma. Thirteen patients were enrolled in this study (9 men and 4 women, with a mean age of 61. 0 years). All patients were given S-1 65mg/m(2) per day for 14 days, and DOC 40-50mg/m(2) by intraarterial infusion was administered. The locoregional response evaluated 3 weeks after administration was 100%, including a 69. 2% complete response. According to Oboshi and Shimosato's classification, histological evaluation of surgical specimens revealed that 3 cases were Grade II a, 4 cases Grade II b, 1 case Grade IV a, and 4 cases Grade IV c. The severe side effects were neutropenia and cerebral infarction. The present study suggests that combination chemotherapy with S-1 and DOC by superselective intra-arterial infusion would be an effective and safe regimen in NAC for oral squamous cell carcinomas.

  18. Pharmacodynamic effects and relationships to plasma and oral fluid pharmacokinetics after intravenous cocaine administration.

    PubMed

    Ellefsen, Kayla N; Concheiro, Marta; Pirard, Sandrine; Gorelick, David A; Huestis, Marilyn A

    2016-06-01

    No controlled cocaine administration data describe cocaine and metabolite disposition in oral fluid (OF) collected with commercially-available collection devices, OF-plasma ratios, and pharmacodynamic relationships with plasma and OF cocaine and metabolite concentrations. Eleven healthy, cocaine-using adults received 25mg intravenous cocaine. Physiological and subjective effects (visual analogue scales), and plasma were collected one hour prior, and up to 21h post-dose. OF was collected with the Quantisal™ device up to 69h post-dose. Cocaine, benzoylecgonine (BE) and ecgonine methyl ester were quantified in plasma by liquid chromatography-tandem mass spectrometry; cocaine and BE were quantified in OF by two dimensional-gas chromatography-mass spectrometry. Increases in heart rate, blood pressure and positive subjective effects occurred within the first 15min, persisting up to 1h ("Rush"), with clockwise hysteresis observed for plasma and OF concentrations and some subjective measures. Peak subjective effects ("Rush," "Good drug effect" and "Bad drug effect") occurred prior to peak OF cocaine concentration, whereas observed peak plasma concentrations and subjective measures occurred simultaneously, most likely due to significantly earlier plasma Tmax compared to OF Tmax.Tlast was generally longer in OF (12.5h cocaine; 33.0h BE) than plasma (9.5h cocaine; >21h BE, cutoffs 1μg/L); 8 and 10μg/L OF cocaine confirmatory cutoffs yielded detection times similar to cocaine's impairing effects, suggesting usefulness for DUID testing. OF offers advantages as an alternative matrix to blood and plasma for identifying cocaine intake, defining pharmacokinetic parameters at different confirmation cutoffs, and aiding different drug testing programs to best achieve their monitoring goals. Copyright © 2016. Published by Elsevier Ireland Ltd.

  19. Antihypertensive effects of continuous oral administration of nattokinase and its fragments in spontaneously hypertensive rats.

    PubMed

    Fujita, Mitsugu; Ohnishi, Katsunori; Takaoka, Shinsaku; Ogasawara, Kazuya; Fukuyama, Ryo; Nakamuta, Hiromichi

    2011-01-01

    To determine whether the antihypertensive effect of nattokinase is associated with the protease activity of this enzyme, we compared nattokinase with the fragments derived from nattokinase, which possessed no protease activity, in terms of the effect on hypertension in spontaneously hypertensive rats (SHR). In the continuous oral administration test, the groups were given a basic diet alone (control), the basic diet containing nattokinase (0.2, 2.6 mg/g diet) or the basic diet containing the fragments derived from nattokinase (0.2, 0.6 mg/g diet). The group fed the basic diet containing high-dosage nattokinase (2.6 mg/g diet) showed significant reductions in systolic blood pressure (SBP), diastolic blood pressure (DBP) and plasma fibrinogen level, compared with control group and no influence on activities of renin and angiotensin-converting enzyme (ACE, EC 3.4.15.1), and plasma angiotensin II level in the renin-angiotensin system. The treatment of the basic diet containing high-dosage fragments (0.6 mg/g diet) significantly decreased SBP, DBP and plasma angiotensin II level in plasma but the treatment did not influence on plasma fibrinogen level. These results suggest that nattokinase and its fragments are different from each other in the mechanism to reduce hypertension. Nattokinase, retained its protease activity after absorbance across the intestines, may decrease blood pressure through cleavage of fibrinogen in plasma. The fragments, which absorbed as nattokinase-degradation products, prevents the elevation of plasma angiotensin II level to suppress hypertension.

  20. Oral administration of rutile and anatase TiO2 nanoparticles shifts mouse gut microbiota structure.

    PubMed

    Li, Juan; Yang, Shengmei; Lei, Runhong; Gu, Weihong; Qin, Yanxia; Ma, Sihan; Chen, Kui; Chang, Yanan; Bai, Xue; Xia, Shibo; Wu, Chongming; Xing, Gengmei

    2018-04-26

    The widespread application of TiO2 nanoparticles (NPs) as additives in foods such as gum, candy and puddings has dramatically increased the human ingestion and accumulation of these nanomaterials. Although the toxicity of TiO2 NPs has been extensively studied, their impact on gut microbiota in vivo still needs further research. In this study, TiO2 NPs with two main crystalline phases anatase and rutile were orally administrated to mice for 28 days. The dynamic influences of anatase and rutile on gut microbiota structures were investigated at doses equivalent to those consumed by people who love to eat candies. The results showed that titanium accumulated in the spleen, lung, and kidney but had no significant effects on organ histology. Gavage of rutile NPs but not anatase NPs resulted in longer intestinal villi and irregular arrangement of villus epithelial cells. Treatment with TiO2 NPs did not decrease gut microbiota diversity but shifted their structures in a time-dependent manner. Rutile NPs had a more pronounced influence on the gut microbiota than anatase NPs. The most influenced phylum was Proteobacteria, which was significantly increased by rutile but not by anatase. At the genus level, Prevotella was significantly decreased by both the TiO2 NPs, Rhodococcus was enriched by rutile NPs, and Bacteroides was increased by anatase NPs. Overall, these results suggested that chronic overconsumption of TiO2 NP-containing foods is likely to deteriorate the gastrointestinal tract and change the structures of microbiota. The crystalline phases may play an important role in mediating the intestinal impact of TiO2 NPs.

  1. Co-administration with cell penetrating peptide enhances the oral bioavailability of docetaxel-loaded nanoparticles.

    PubMed

    Bu, Xiangyuan; Zhu, Tao; Ma, Yiran; Shen, Qi

    2015-05-01

    This study proposes a novel docetaxel (DTX) cyclodextrin inclusion-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (D-CNPs) system with cell penetrating peptide (CPP), and evaluates its potential for oral administration of DTX. Heptaarginine (R7) was used as the CPP. D-CNPs were prepared by the double-emulsification method. The mean particle size and zeta potential of the resulting D-CNPs were 198.7 ± 12.56 nm and -27.25 ± 4.62 mV, respectively, and their mean encapsulation efficiency and drug loading were 80.35 ± 6.37% and 1.02 ± 0.15%, respectively. The morphology of the D-CNPs was observed by scanning electron microscope (SEM) and transmission electron microscope (TEM). The release behavior of the D-CNPs was studied by using the dialysis method. The relative bioavailability of D-CNPs and D-CNPs co-administered with R7 was enhanced about 5.57- and 9.43-fold, respectively, compared with the free DTX suspension. Furthermore, D-CNPs with R7 displayed maximum cytotoxicity against MCF-7 cells in MTT assay. D-CNPs co-administered with R7 showed markedly higher fluorescence intensity than D-CNPs without CPP. The results suggest that the D-CNPs co-administered with R7 could be a potential delivery system with excellent therapeutic efficacy for targeting the drugs to cancer cells.

  2. Cost-effectiveness analysis of exenatide twice daily (BID) vs insulin glargine once daily (QD) as add-on therapy in Chinese patients with Type 2 diabetes mellitus inadequately controlled by oral therapies.

    PubMed

    Deng, Jing; Gu, Shuyan; Shao, Hui; Dong, Hengjin; Zou, Dajin; Shi, Lizheng

    2015-01-01

    To estimate cost-effectiveness of exenatide twice daily (BID) vs insulin glargine once daily (QD) as add-on therapy in Chinese type 2 diabetes patients not well controlled by oral anti-diabetic (OAD) agents. The Cardiff model was populated with data synthesized from three head-to-head randomized clinical trials of up to 30 weeks in China comparing exenatide BID vs insulin glargine as add-on therapies to oral therapies in the Chinese population. The Cardiff model generated outputs including macrovascular and microvascular complications, diabetes-specific mortality, costs, and quality-adjusted life years (QALYs). Cost and QALYs were estimated with a time horizon of 40 years at a discount rate of 3% from a societal perspective. Compared with insulin glargine plus OAD treatments, patients on exenatide BID plus OAD gained 1.88 QALYs, at an incremental cost saving of Chinese Renminbi (RMB) 114,593 (i.e., cost saving of RMB 61078/QALY). The cost-effectiveness results were robust to various sensitivity analyses including probabilistic sensitivity analysis. The variables with the most impact on incremental cost-effectiveness ratio included HbA1c level at baseline, health utilities decrement, and BMI at baseline. Compared with insulin glargine QD, exenatide BID as add-on therapy to OAD is a cost-effective treatment in Chinese patients inadequately controlled by OAD treatments.

  3. Oral administration of Lactobacillus paracasei NCC 2461 for the modulation of grass pollen allergic rhinitis: a randomized, placebo-controlled study during the pollen season.

    PubMed

    Nembrini, Chiara; Singh, Anurag; De Castro, Carlos Antonio; Mercenier, Annick; Nutten, Sophie

    2015-01-01

    The efficacy of Lactobacillus paracasei NCC 2461 in modulating allergic rhinitis was previously evaluated in two exploratory clinical studies. Oral administration with NCC 2461 reduced specific subjective symptoms following nasal provocation tests with controlled grass pollen allergen concentrations. Our aim was to confirm the anti-allergic effect of NCC 2461 in grass pollen allergic subjects exposed to natural doses of allergens during the pollen season. A double-blind, randomized, placebo-controlled, parallel study was conducted with 131 grass pollen allergic subjects from May to July 2012 in concomitance with the pollen season in Berlin. NCC 2461 or placebo was administered daily for an 8-week period to adult subjects with clinical history of allergic rhinitis to grass pollen, positive skin prick test and IgE to grass pollen. During the 8 weeks, symptoms and quality of life questionnaires were filled out, and plasma was collected for IgE analysis at screening and at the end of the intervention. All subjects were included within a 5-day interval, ensuring exposure to similar air pollen counts for each individual during the trial period. The results obtained show that symptoms increased with pollen loads, confirming a natural exposure to the allergen and presence of pollen-induced allergic rhinitis in the subjects. However, no significant differences were observed in allergic rhinitis symptoms scores, quality of life, or specific IgE levels between subjects receiving NCC 2461 as compared to placebo administration. In contrast to previous findings, oral administration of NCC 2461 did not show a beneficial effect on allergic rhinitis in a field trial. The influence of study design, allergen exposure and intervention window on the efficacy of NCC 2461 in modulating respiratory allergy should be further evaluated.

  4. Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo.

    PubMed

    He, Wen-Bin; Abe, Kazuho; Akaishi, Tatsuhiro

    2018-01-01

    To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP) at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin) tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to inhibit its effect in hippocampal slices in vitro. These results suggest that orally administered fisetin crosses the blood-brain barrier and promotes synaptic functions in the hippocampus. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  5. Physicochemical characterisation of fluids and soft foods frequently mixed with oral drug formulations prior to administration to children.

    PubMed

    Kersten, E; Barry, A; Klein, S

    2016-03-01

    Oral drug administration to children poses specific pharmaceutical challenges that are often not seen to the same extent in adults, and whose occurrence may also be age dependent. When an age-appropriate dosage form is not available, manipulation of adult dosage forms (e.g., splitting and crushing of tablets or opening of capsules) has been reported as a means to facilitate administration to children. To enhance swallowability and/or mask an unpleasant taste of the dosage form to be administered, crushed/split tablets or the contents of capsules are often mixed with food or drinks or suspended in a vehicle prior to administration. However, it seems that the risks and benefits of an approach whereby the dosage form is modified prior to administration in this manner are everything but clear. The aim of the present study was to gain an overview of the physicochemical properties of a number of fluids, soft foods and suspension vehicles that are commonly reported to be mixed with oral medications before administration to children to improve patient acceptability. For this purpose, physicochemical parameters of 15 different fluids, soft foods and suspension vehicles were measured. These included pH, buffer capacity, osmolality, surface tension and viscosity. Results of the study clearly show the differences in physicochemical properties of the test candidates. It is thus obvious that the type of fluid/food mixed with a drug product before administration may have a significant impact on bioavailability of the drug administered. Therefore, a risk-based assessment of such practices considering API properties, formulation features and physicochemical properties of the fluids and foods intended to be co-administered with the dosage form, in conjunction with the anatomical and physiological maturity of the gastro-intestinal tract in the intended paediatric population, should be an essential part of paediatric oral formulation development.

  6. Antihypertensive effect of long-term oral administration of jellyfish (Rhopilema esculentum) collagen peptides on renovascular hypertension.

    PubMed

    Zhuang, Yongliang; Sun, Liping; Zhang, Yufeng; Liu, Gaoxiang

    2012-02-01

    Antihypertensive effect of long-term oral administration of jellyfish (Rhopilema esculentum) collagen peptides (JCP) on renovascular hypertension rats (RVHs) was evaluated. The systolic blood pressure and diastolic blood pressure of the RVHs were significantly reduced with administration of JCP (p < 0.05), compared with model control group. However, the arterial blood pressure of normal rats showed no significant changes during long-term oral treatment with high dose JCP (p > 0.05). Furthermore, effect of JCP on angiotensin II (Ang II) concentration of plasma had no significance (p > 0.05), but JCP significantly inhibited the Ang II concentration in RVHs' kidney (p < 0.05). The kidney should be the target site of JCP.

  7. Antihypertensive Effect of Long-Term Oral Administration of Jellyfish (Rhopilema esculentum) Collagen Peptides on Renovascular Hypertension

    PubMed Central

    Zhuang, Yongliang; Sun, Liping; Zhang, Yufeng; Liu, Gaoxiang

    2012-01-01

    Antihypertensive effect of long-term oral administration of jellyfish (Rhopilema esculentum) collagen peptides (JCP) on renovascular hypertension rats (RVHs) was evaluated. The systolic blood pressure and diastolic blood pressure of the RVHs were significantly reduced with administration of JCP (p < 0.05), compared with model control group. However, the arterial blood pressure of normal rats showed no significant changes during long-term oral treatment with high dose JCP (p > 0.05). Furthermore, effect of JCP on angiotensin II (Ang II) concentration of plasma had no significance (p > 0.05), but JCP significantly inhibited the Ang II concentration in RVHs’ kidney (p < 0.05). The kidney should be the target site of JCP. PMID:22412809

  8. Pharmacokinetics and metabolism of benzene in Zymbal gland and other key target tissues after oral administration in rats.

    PubMed Central

    Low, L K; Meeks, J R; Norris, K J; Mehlman, M A; Mackerer, C R

    1989-01-01

    Solid tumors have been reported in the Zymbal gland, oral and nasal cavities, and mammary gland of Sprague-Dawley rats following chronic oral administration of benzene. The cause for the specificity of such lesions remains unclear, but it is possible that tissue-specific metabolism or pharmacokinetics of benzene is responsible. Metabolism and pharmacokinetic studies were carried out in our laboratory with 14C-benzene at oral doses of 0.15 to 500 mg/kg to ascertain tissue retention, metabolite profile, and elimination kinetics in target and nontarget organs and in blood. Findings from those studies indicate the following: a) the Zymbal gland is not a sink or a site of accumulation for benzene or its metabolites even after a single high dose (500 mg/kg) or after repeated oral administration; b) the metabolite profile is quantitatively different in target tissues (e.g., Zymbal gland, nasal cavity), nontarget tissues and blood; and (c) pharmacokinetic studies show that the elimination of radioactivity from the Zymbal gland is biphasic. PMID:2792043

  9. Combining two technologies: multifunctional polymers and self-nanoemulsifying drug delivery system (SNEDDS) for oral insulin administration.

    PubMed

    Sakloetsakun, Duangkamon; Dünnhaupt, Sarah; Barthelmes, Jan; Perera, Glen; Bernkop-Schnürch, Andreas

    2013-10-01

    The aim of the study is to develop a self-nanoemulsifying drug delivery system (SNEDDS) based on thiolated chitosan for oral insulin administration. The preparations were characterized by particle size, entrapment efficiency, stability and drug release. Serum insulin concentrations were determined after oral administration of all formulations. Insulin SNEDDS formulation was served as control. The optimized SNEDDS consists of 65% (w/w) miglyol 840, 25% (w/w) cremophor EL, 10% (w/w) co-solvents (a mixture of DMSO and glycerol). The formulations in the presence or absence of insulin (5mg/mL) were spherical with the size range between 80 and 160 nm. Entrapment efficiency of insulin increased significantly when the thiolated chitosan was employed (95.14±2.96%), in comparison to the insulin SNEDDS (80.38±1.22%). After 30 min, the in vitro release profile of insulin from the nanoemulsions was markedly increased compared to the control. In vivo results showed that insulin/thiolated chitosan SNEDDS displayed a significant increase in serum insulin (p-value=0.02) compared to oral insulin solution. A new strategy to combine SNEDDS and thiolated chitosan described in the study would therefore be a promising and innovative approach to improve oral bioavailability of insulin. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  10. Recovery Effects of Oral Administration of Glucosylceramide and Beet Extract on Skin Barrier Destruction by UVB in Hairless Mice.

    PubMed

    Tokudome, Yoshihiro; Masutani, Noriomi; Uchino, Shohei; Fukai, Hisano

    2017-10-27

    Purified glucosylceramide from beet extract (beet GlcCer) and beet extract containing an equal amount of GlcCer were administered orally to ultra violet B (UVB)-irradiated mice, and differences in the protective effects against skin barrier dysfunction caused by UVB irradiation were compared. In the beet GlcCer group, epidermal thickening and the decrease in stratum corneum (SC) ceramide content caused by UVB irradiation were reduced. In the group that was orally administered beet extract containing glucosylceramide, effects similar to those in the beet GlcCer group were observed. Oral administration of beet GlcCer had no obvious effects against an increase in TEWL or decrease in SC water content after UVB irradiation, but there was improvement in the beet extract group. Oral administration of beet GlcCer is effective in improving skin barrier function in UVB-irradiated mice. Beet extract contains constituents other than GlcCer that are also effective in improving skin barrier function.

  11. Changes in plasma glucose in Otsuka Long-Evans Tokushima Fatty rats after oral administration of maple syrup.

    PubMed

    Nagai, Noriaki; Yamamoto, Tetsushi; Tanabe, Wataru; Ito, Yoshimasa; Kurabuchi, Satoshi; Mitamura, Kuniko; Taga, Atsushi

    2015-01-01

    We investigate whether maple syrup is a suitable sweetener in the management of type 2 diabetes using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The enhancement in plasma glucose (PG) and glucose absorption in the small intestine were lower after the oral administration of maple syrup than after sucrose administration in OLETF rats, and no significant differences were observed in insulin levels. These data suggested that maple syrup might inhibit the absorption of glucose from the small intestine and preventing the enhancement of PG in OLETF rats. Therefore, maple syrup might help in the prevention of type 2 diabetes.

  12. A Case Report of Post-Operative Jöd-Basedow Phenomennon Following Oral and IV Iodine Contrast Administration

    PubMed Central

    Hull, Erroll; Lujan, Eugenio

    2014-01-01

    This is a case of thyrotoxicosis, due to the Jöd-Basedow phenomenon following administration of oral and IV iodinated contrast in a patient with history of gastrointestinal stromal tumor (GIST) and small bowel obstruction. The patient developed atrial fibrillation and had an extended stay in the intensive care unit. Given the aging population with possible subclinical hyperthyroidism, multinodular goiter, and the rise in contrast administration for routine diagnostic studies, this case serves to raise awareness of the risks of “routine” tests administered to our aging patient population. PMID:24716009

  13. Daily and Nondaily Oral Preexposure Prophylaxis in Men and Transgender Women Who Have Sex With Men: The Human Immunodeficiency Virus Prevention Trials Network 067/ADAPT Study.

    PubMed

    Grant, Robert M; Mannheimer, Sharon; Hughes, James P; Hirsch-Moverman, Yael; Loquere, Avelino; Chitwarakorn, Anupong; Curlin, Marcel E; Li, Maoji; Amico, K Rivet; Hendrix, Craig W; Anderson, Peter L; Dye, Bonnie J; Marzinke, Mark A; Piwowar-Manning, Estelle; McKinstry, Laura; Elharrar, Vanessa; Stirratt, Michael; Rooney, James F; Eshleman, Susan H; McNicholl, Janet M; van Griensven, Frits; Holtz, Timothy H

    2018-05-17

    Nondaily dosing of oral preexposure prophylaxis (PrEP) may provide equivalent coverage of sex events compared with daily dosing. At-risk men and transgender women who have sex with men were randomly assigned to 1 of 3 dosing regimens: 1 tablet daily, 1 tablet twice weekly with a postsex dose (time-driven), or 1 tablet before and after sex (event-driven), and were followed for coverage of sex events with pre- and postsex dosing measured by weekly self-report, drug concentrations, and electronic drug monitoring. From July 2012 to May 2014, 357 participants were randomized. In Bangkok, the coverage of sex events was 85% for the daily arm compared with 84% for the time-driven arm (P = .79) and 74% for the event-driven arm (P = .02). In Harlem, coverage was 66%, 47% (P = .01), and 52% (P = .01) for these groups. In Bangkok, PrEP medication concentrations in blood were consistent with use of ≥2 tablets per week in >95% of visits when sex was reported in the prior week, while in Harlem, such medication concentrations occurred in 48.5% in the daily arm, 30.9% in the time-driven arm, and 16.7% in the event-driven arm (P < .0001). Creatinine elevations were more common in the daily arm (P = .050), although they were not dose limiting. Daily dosing recommendations increased coverage and protective drug concentrations in the Harlem cohort, while daily and nondaily regimens led to comparably favorable outcomes in Bangkok, where participants had higher levels of education and employment. NCT01327651.

  14. Dose-response relationship of an environmental mixture of pyrethroids following an acute oral administration in the rat

    EPA Science Inventory

    Dose-response relationship of an environmental mixture of pyrethroids following an acute oral administration in the rat M.F. Hughes1, D.G. Ross1, J.M. Starr1, E.J. Scollon1,2, M.J. Wolansky1,3, K.M. Crofton1, M.J. DeVito1,4 1U.S. EPA, ORD, Research Triangle Park, NC, 2U.S. EPA,...

  15. Drug distribution in man: a positron emission tomography study after oral administration of the labelled neuroprotective drug vinpocetine.

    PubMed

    Gulyás, Balázs; Halldin, Christer; Sóvágó, Judit; Sandell, Johan; Cselényi, Zsolt; Vas, Adám; Kiss, Béla; Kárpáti, Egon; Farde, Lars

    2002-08-01

    Direct information on the distribution of a drug requires measurements in various tissues. Such data have until now been obtained in animals, or have indirectly been calculated from plasma measurements in humans using mathematical models. Here we suggest the use of positron emission tomography (PET) as a method to obtain direct measurements of drug distribution in the human body. The distribution in body and brain of vinpocetine, a neuroprotective drug widely used in the prevention and treatment of cerebrovascular diseases, was followed after oral administration. Vinpocetine was labelled with carbon-11 and radioactivity was measured by PET in stomach, liver, brain and kidney in six healthy volunteers. The radioactivity in blood and urine as well as the fractions of [(11)C]vinpocetine and labelled metabolites in plasma were also determined. After oral administration, [(11)C]vinpocetine appeared immediately in the stomach and within minutes in the liver and the blood. In the blood the level of radioactivity continuously increased until the end of the measurement period, whereas the fraction of the unchanged mother compound decreased. Radioactivity uptake and distribution in the brain were demonstrable from the tenth minute after the administration of the labelled drug. Brain distribution was heterogeneous, similar to the distribution previously reported after intravenous administration. These findings indicate that vinpocetine, administered orally in humans, readily enters the bloodstream from the stomach and gastrointestinal tract and, consequently, passes the blood-brain barrier and enters the brain. Radioactivity from [(11)C]vinpocetine was also demonstrated in the kidneys and in urine, indicating that at least a part of the radioactive drug and labelled metabolites is eliminated from the body through the kidneys. This study is the first to demonstrate that PET might be a useful, direct and non-invasive tool to study the distribution and pharmacokinetics of orally

  16. Sex and menstrual cycle effects on chronic oral cocaine self-administration in rhesus monkeys: Effects of a nondrug alternative reward.

    PubMed

    Carroll, Marilyn E; Collins, Molly; Kohl, Emily A; Johnson, Seth; Dougen, Ben

    2016-08-01

    In previous studies, female monkeys self-administered more oral phencyclidine (PCP) than males, and PCP intake differed by phase of menstrual cycle. The purpose of this study was to examine sex and hormonal influences on oral cocaine self-administration in male and female rhesus monkeys in the follicular vs. luteal phases of the menstrual cycle, with concurrent access to an alternative nondrug reward, saccharin (SACC) vs. water. Concurrent access to cocaine (0.2, 0.4, and 0.8 mg/ml) and SACC or water was available from two drinking spouts under concurrent fixed-ratio (FR) 2, 4, and 8 schedules during daily 3-h sessions. Cocaine deliveries were similar in males and females in the females' luteal phase, but cocaine deliveries were higher in females during the follicular phase than the luteal phase and compared to males. When SACC was available, cocaine deliveries were reduced in females in the follicular phase of the cycle, and cocaine intake (mg/kg) was reduced in males and in females' follicular and luteal phases. Access to concurrent SACC (vs. water) reduced cocaine intake (mg/kg) in males and in females during both menstrual phases, and the magnitude of the reduction in cocaine intake was greatest during the females' follicular phase. Thus, a nondrug alternative reward, SACC, is a viable alternative treatment for reducing cocaine's rewarding effects on male and female monkeys, and reductions in cocaine seeking were optimal in the females' luteal phase.

  17. Oral Administration of β-1,3/1,6-Glucan to Dogs Temporally Changes Total and Antigen-Specific IgA and IgM▿

    PubMed Central

    Stuyven, E.; Verdonck, F.; Van Hoek, I.; Daminet, S.; Duchateau, L.; Remon, J. P.; Goddeeris, B. M.; Cox, E.

    2010-01-01

    The effect of oral administration of β-1,3/1,6-glucans from Saccharomyces cerevisiae on humoral immunity in domestic dogs is not known. In this study, 15 beagle dogs were orally given MacroGard tablets, which contain 150 mg of this β-glucan, daily for 4 weeks. At the end of this period, the total serum immunoglobulin A (IgA) level decreased significantly in the group treated with the glucan compared to that in the control group as well as compared to the concentrations before supplementation. In contrast, the total serum IgM level rose significantly, whereas no effect on the IgG level occurred. Similar changes were seen in Bordetella-specific IgA and IgM titers following vaccination during the supplementation period. The IgA concentration also became significantly lower in the saliva and tears of the glucan group than in the placebo group. The effects disappeared 1 week after the cessation of the supplementation. In conclusion, the results showed a temporary change in the isotype profile during glucan supplementation. PMID:20032218

  18. Comparative pharmacokinetics of oxytetracycline in blunt-snout bream (Megalobrama amblycephala) with single and multiple-dose oral administration.

    PubMed

    Li, Ru-Qin; Ren, Yu-Wei; Li, Jing; Huang, Can; Shao, Jun-Hui; Chen, Xiao-Xuan; Wu, Zhi-Xin

    2015-06-01

    Research into the pharmacokinetics and residue elimination of oxytetracycline (OTC) is important both to determine the optimal dosage regimens and to establish a safe withdrawal time in fish. A depletion study is presented here for OTC in Megalobrama amblycephala with a single-dose (100 mg/kg) and multiple-dose (100 mg/kg for five consecutive days) oral administration. The study was conducted at 25 °C. As a result, a one-compartment model was developed. For the single dose, the absorption half-life was 5.79, 9.40, 6.96, and 8.06 h in the plasma, liver, kidney, and muscle, respectively. However, the absorption half-life was 3.62, 7.33, 4.59, and 6.02 h with multiple-dose oral administration. The elimination half-time in the plasma, liver, kidney, and muscle was 58.63, 126.43, 65.1, and 58.85 h when M. amblycephala was treated with a single dose. However, the elimination half-time changed to 91.75, 214.87, 126.22, and 135.84 h with multiple-dose oral administration.

  19. Halloysite Nanotubes-Induced Al Accumulation and Fibrotic Response in Lung of Mice after 30-Day Repeated Oral Administration.

    PubMed

    Wang, Xue; Gong, Jiachun; Rong, Rui; Gui, Zongxiang; Hu, Tingting; Xu, Xiaolong

    2018-03-21

    Natural halloysite (Al 2 Si 2 O 5 (OH) 4 · nH 2 O) nanotubes (HNT) are clay materials with hollow tubular structure and are widely applied in many fields. Many in vitro studies indicate that HNTs exhibit a high level of biocompatibility; however, the in vivo toxicity of HNTs remains unclear. In this study, the biodistribution and pulmonary toxicity of the purified HNTs in mice were investigated after intragastric administration for 30 days. HNTs have high stability in biological conditions. Oral administration of HNTs caused significant Al accumulation predominantly in the lung with relative slight effects on Si biodistribution. Oral administration of HNTs stimulated the growth of the mice at low dose (5 mg/kg BW) with no pulmonary toxicity but inhibited the mouse growth and resulted in oxidative stress and inflammation in lung at high dose (50 mg/kg BW). In addition, oral HNTs at high dose could be absorbed from the gastrointestinal tract and deposited in lung and could also induce pulmonary fibrosis.

  20. The antinociceptive effects of Monechma ciliatum and changes in EEG waves following oral and intrathecal administration in rats

    NASA Astrophysics Data System (ADS)

    Meraiyebu, Ajibola B.; Adelaiye, Alexander B.; O, Odeh S.

    2010-02-01

    The research work was carried out to study the effect of Oral and Intrathecal Monechma Ciliatum on antinociception and EEG readings in Wistar Rats. Traditionally the extract is given to women in labour believed to reduce pain and ease parturition, though past works show that it has oesteogenic and oxytotic effects. The rats were divided into 5 major groups. Group 1 served as oral control group while groups 2 and 3 served as oral experimental groups and were treated with 500mg/kg and 1000mg/kg monechma ciliatum respectively. Group 4 served as intrathecal control group treated with intrathecal dextrose and group 5 received 1000mg/kg Monechma Ciliatrum intrathecally. The antinociceptive effect was analysed using a Von Frey's aesthesiometer. Monechma Ciliatum showed significant antinociceptive effect both orally and intrathecally, although it had a greater effect orally and during the first 15 minutes of intrathecal administration. EEG readings were also taken for all the groups and there was a decrease in amplitude and an increase in frequency for high dose (1000mg/ml) experimental groups and the mid brain electrodes produced a change from theta waves (3.5 - 7 waves per second) to alpha waves (7.5 - 13 waves per second) as seen in relaxed persons and caused decreased amplitudes and change in distribution seen in beta waves. Properties similarly accentuated by sedativehypnotic drugs.

  1. Oral and intraperitoneal administration of quercetin decreased lymphocyte DNA damage and plasma lipid peroxidation induced by TSA in vivo.

    PubMed

    Chan, Shu-Ting; Lin, Yi-Chin; Chuang, Cheng-Hung; Shiau, Rong-Jen; Liao, Jiunn-Wang; Yeh, Shu-Lan

    2014-01-01

    Our previous study showed that quercetin enhances the anticancer effect of trichostatin A (TSA) in xenograft mice given quercetin intraperitoneally (10 mg/kg, 3 times/week). Herein, we investigate whether quercetin administered orally exerts such an effect and prevents the cytotoxic side effects of TSA. We found that quercetin given orally (20 and 100 mg/kg, 3 times/week) failed to enhance the antitumor effect of TSA although it increased the total quercetin concentration more than quercetin administered intraperitoneally in the plasma. The compound quercetin-3-glucuronide (Q3G) increased the most. However, quercetin administered intraperitoneally increased the total quercetin level in tumor tissues more than oral quercetin. Oral and intraperitoneal administration of quercetin similarly decreased lymphocyte DNA damage and plasma lipid peroxidation level induced by TSA. Furthermore, we found that the enhancing effect of Q3G on the antitumor effect of TSA and the incorporation of Q3G was less than that of quercetin in A549 cells. However, we found that A549 cells possessed the ability to convert Q3G to quercetin. In conclusion, different from quercetin administered intraperitoneally, quercetin administered orally failed to enhance the antitumor effect of TSA because of its metabolic conversion. However, it prevented TSA-induced DNA damage and lipid peroxidation.

  2. Oral and Intraperitoneal Administration of Quercetin Decreased Lymphocyte DNA Damage and Plasma Lipid Peroxidation Induced by TSA In Vivo

    PubMed Central

    Chan, Shu-Ting; Shiau, Rong-Jen; Liao, Jiunn-Wang; Yeh, Shu-Lan

    2014-01-01

    Our previous study showed that quercetin enhances the anticancer effect of trichostatin A (TSA) in xenograft mice given quercetin intraperitoneally (10 mg/kg, 3 times/week). Herein, we investigate whether quercetin administered orally exerts such an effect and prevents the cytotoxic side effects of TSA. We found that quercetin given orally (20 and 100 mg/kg, 3 times/week) failed to enhance the antitumor effect of TSA although it increased the total quercetin concentration more than quercetin administered intraperitoneally in the plasma. The compound quercetin-3-glucuronide (Q3G) increased the most. However, quercetin administered intraperitoneally increased the total quercetin level in tumor tissues more than oral quercetin. Oral and intraperitoneal administration of quercetin similarly decreased lymphocyte DNA damage and plasma lipid peroxidation level induced by TSA. Furthermore, we found that the enhancing effect of Q3G on the antitumor effect of TSA and the incorporation of Q3G was less than that of quercetin in A549 cells. However, we found that A549 cells possessed the ability to convert Q3G to quercetin. In conclusion, different from quercetin administered intraperitoneally, quercetin administered orally failed to enhance the antitumor effect of TSA because of its metabolic conversion. However, it prevented TSA-induced DNA damage and lipid peroxidation. PMID:24868531

  3. Oral Fluid and Plasma 3,4-Methylenedioxymethamphetamine (MDMA) and Metabolite Correlation after Controlled Oral MDMA Administration

    PubMed Central

    Desrosiers, Nathalie A.; Barnes, Allan J.; Hartman, Rebecca L.; Scheidweiler, Karl B.; Kolbrich-Spargo, Erin A.; Gorelick, David A.; Goodwin, Robert S.; Huestis, Marilyn A.

    2013-01-01

    Oral fluid (OF) offers a non-invasive sample collection for drug testing. However, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) in OF has not been adequately characterized in comparison to plasma. We administered oral low (1.0 mg/kg) and high (1.6 mg/kg) dose MDMA to 26 participants and collected simultaneous OF and plasma specimens for up to 143 h after dosing. We compared OF/plasma (OF/P) ratios, time of initial detection (tfirst), maximal concentrations (Cmax), time of peak concentrations (tmax), time of last detection (tlast), clearance, and 3,4-methylenedioxyamphetamine (MDA) to MDMA ratios over time. For OF MDMA and MDA, Cmax was higher, tlast was later, and clearance was slower compared to plasma. For OF MDA only, tfirst was later compared to plasma. Median (range) OF/P ratios were 5.6 (0.1-52.3) for MDMA and 3.7 (0.7-24.3) for MDA. OF and plasma concentrations were weakly but significantly correlated (MDMA R2= 0.438, MDA R2= 0.197, p<0.0001). Median OF/P ratios were significantly higher following high dose: MDMA low 5.2 (0.1-40.4) and high 6.0 (0.4-52.3) (p<0.05); MDA low 3.3 (0.7-17.1) and high 4.1 (0.9-24.3) (p<0.001). There was large inter-subject variation in OF/P ratios. MDA/MDMA ratios in plasma were higher than those in OF (p<0.001), and MDA/MDMA ratios significantly increased over time in OF and plasma. MDMA and MDA concentrations were higher in OF than in plasma. OF and plasma concentrations were correlated, but large inter-subject variability precludes estimation of plasma concentrations from OF. PMID:23471370

  4. Metal ion-oxytetracycline pharmacokinetic interactions after oral co-administration in broiler chickens.

    PubMed

    Ziółkowski, H; Jasiecka, A; Zuśka-Prot, M; Przybysz, J; Grabowski, T; Jaroszewski, J J

    2016-08-01

    The influence of the composition of calcium (Ca(2+)), magnesium (Mg(2+)), and iron (Fe(3+)) ions in two concentration levels (low-500 mg/L of CaCl2, 125 mg/L of MgCl2, and 10 mg/L of FeCl3 and high-2,500 mg/L of CaCl2, 625 mg/L of MgCl2, and 50 mg/L of FeCl3) contained in water on the pharmacokinetics (PK) of oxytetracycline (OTC) was determined. OTC hydrochloride was administered at a dose of 25 mg/kg of body weight to broiler chickens divided into four groups of nine birds each, including 3 oral groups (in deionized water -control, in water with low ion concentration, and in water with high ion concentration) and 1 intravenous group. OTC concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry, after which non-compartmental pharmacokinetic analysis was conducted.The absolute bioavailability of OTC in the group of birds exposed to higher ions concentration was reduced (8.68% ± 2.56) as compared to the control (13.71% ± 2.60). Additionally, in this group, decrease in PK parameters such as: area under the concentration-time curve from 0 to infinity (15.36 μg × h/mL ± 4.36), from 0 to t (14.78 μg × h/mL ± 4.37), area under the first moment of curve from 0 to t (107.54 μg × h/mL ± 36.48), and maximum plasma concentration (2.13 μg/mL ± 0.32) were also observed. It is noteworthy, all mentioned parameters demonstrated a downward trend with high correlation coefficient (P = 0.004, P = 0.002, P = 0.005, P = 0.004, P = 0.011, respectively), reflecting the influence of increasing concentrations of Ca(2+), Mg(2+), and Fe(3+) ions on the decreasing absorption rate of OTC.Based on the current research results, it can be assumed that high concentrations of several ions applied concomitantly are able to decrease the absorption of OTC from gastrointestinal tract in broiler chickens. This occurrence might impair the drug's clinical efficacy toward some pathogenic microorganisms. It implies that using OTC on a farm may require

  5. Pharmacokinetics of mequindox and one of its major metabolites in chickens after intravenous, intramuscular and oral administration.

    PubMed

    Ding, Huanzhong; Liu, Yingchun; Zeng, Zhenling; Si, Hongbin; Liu, Kaiyong; Liu, Yiming; Yang, Fan; Li, Yafei; Zeng, Dongping

    2012-08-01

    Pharmacokinetics of mequindox and one of its major metabolites (M) was determined in chickens after intravenous (i.v.), intramuscular (i.m.) and oral administration of mequindox at a single dose of 10 (i.v. and i.m.) or 20 mg/kg b.w. (oral). Plasma concentration profiles were analyzed by a non-compartmental pharmacokinetic method. Following i.v., i.m. and oral administration, the areas under the plasma concentration-time curve (AUC(0-∞)) were 0.71±0.15, 0.67±0.21, 0.25±0.10 μg h/mL (mequindox) and 37.24±7.98, 36.40±9.16, 86.39±16.01 μg h/mL (M), respectively. The terminal elimination half-lives (t(1/2λz)) were determined to be 0.15±0.06, 0.21±0.09, 0.49±0.23 h (mequindox) and 5.36±0.86, 5.39±0.52, 5.22±0.35 h (M), respectively. The bioavailabilities (F) of mequindox were 89.4% and 16.6% for i.m. and oral administration. Steady-state distribution volume (V(ss)) of 1.20±0.34 L/kg and total body clearance (Cl(B)) of 13.57±2.16 L/kg h were determined for mequindox after i.v. dosing. After single i.m. and oral administration, peak plasma concentrations (C(max)) of 3.04±1.32, 0.36±0.13 μg/mL (mequindox) and 3.81±0.92, 5.99±1.16 μg/mL (M) were observed at t(max) of 0.08±0.02, 0.32±0.12 h (mequindox) and 0.66±0.19, 6.67±1.03 h (M), respectively. The results showed that mequindox was rapidly absorbed after i.m. or p.o. administration and most of mequindox was transformed to metabolites in chickens, with much higher C(max)s and AUCs of metabolite (M) than those of mequindox in plasma. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Oral conditions and dysphagia in Japanese, community-dwelling middle- and older- aged adults, independent in daily living.

    PubMed

    Inui, Akinari; Takahashi, Ippei; Kurauchi, Sizuka; Soma, Yuki; Oyama, Toshiaki; Tamura, Yoshihiro; Noguchi, Takao; Murashita, Kouichi; Nakaji, Shigeyuki; Kobayashi, Wataru

    2017-01-01

    Prevention, early detection and effective rehabilitation of dysphagia are important issues to be considered in an aging society. Previous studies have shown conflicting findings regarding the association between dysphagia and its potential risk factors, including age, malnutrition, oral conditions, lifestyle and medical history. Herein, we assessed the prevalence and association of dysphagia with potential risk factors in 50- to 79-year-old adults dwelling in a community in Japan. In this study, there were 532 participants (185 males and 347 females). Participants who responded positively to the question "Do you sometimes choke on drinks/food such as tea and soup?" or those who presented with abnormal repetitive saliva swallowing test findings were diagnosed with dysphagia. The data collected from these participants included the following: number of teeth, occurrence of oral dryness, age, body mass index, serum albumin concentration, smoking, drinking and exercise habits, presence of diseases, such as diabetes mellitus and hypertension, and questions from the Mini-Mental State Examination. Dysphagia was observed in 33 males (17.8%) and 76 females (21.9%). To explore the effect of the potential risk factors on the prevalence of dysphagia, a model was built by multivariate logistic regression analysis. Using the forced entry method, oral dryness (odds ratio [OR] =3.683 and P =0.003 in males; OR =1.797 and P =0.032 in females) and the number of teeth (OR =0.946 and P =0.038 in males) were found to be significantly related to dysphagia. This cross-sectional study demonstrated associations between oral conditions and dysphagia. Factors such as oral dryness and number of teeth may contribute to dysphagia more so than aging, lifestyle and comorbidity in community-dwelling adults over the age of 50.

  7. Oral conditions and dysphagia in Japanese, community-dwelling middle- and older- aged adults, independent in daily living

    PubMed Central

    Inui, Akinari; Takahashi, Ippei; Kurauchi, Sizuka; Soma, Yuki; Oyama, Toshiaki; Tamura, Yoshihiro; Noguchi, Takao; Murashita, Kouichi; Nakaji, Shigeyuki; Kobayashi, Wataru

    2017-01-01

    Purpose Prevention, early detection and effective rehabilitation of dysphagia are important issues to be considered in an aging society. Previous studies have shown conflicting findings regarding the association between dysphagia and its potential risk factors, including age, malnutrition, oral conditions, lifestyle and medical history. Herein, we assessed the prevalence and association of dysphagia with potential risk factors in 50- to 79-year-old adults dwelling in a community in Japan. Patients and methods In this study, there were 532 participants (185 males and 347 females). Participants who responded positively to the question “Do you sometimes choke on drinks/food such as tea and soup?” or those who presented with abnormal repetitive saliva swallowing test findings were diagnosed with dysphagia. The data collected from these participants included the following: number of teeth, occurrence of oral dryness, age, body mass index, serum albumin concentration, smoking, drinking and exercise habits, presence of diseases, such as diabetes mellitus and hypertension, and questions from the Mini–Mental State Examination. Results Dysphagia was observed in 33 males (17.8%) and 76 females (21.9%). To explore the effect of the potential risk factors on the prevalence of dysphagia, a model was built by multivariate logistic regression analysis. Using the forced entry method, oral dryness (odds ratio [OR] =3.683 and P=0.003 in males; OR =1.797 and P=0.032 in females) and the number of teeth (OR =0.946 and P=0.038 in males) were found to be significantly related to dysphagia. Conclusion This cross-sectional study demonstrated associations between oral conditions and dysphagia. Factors such as oral dryness and number of teeth may contribute to dysphagia more so than aging, lifestyle and comorbidity in community-dwelling adults over the age of 50. PMID:28352164

  8. Kinetics of absorption and elimination of ofloxacin in humans after oral and rectal administrations.

    PubMed

    Eboka, C J; Okor, R S; Akerele, J O; Aigbavboa, S O

    1997-06-01

    Ofloxacin pharmacokinetics have been studied in four healthy subjects after a single oral or rectal dose, each of 200 mg. For the oral dose tmax was about 2 h, Cmax 1.96 +/- 0.56 micrograms/ml and AUC1-15 15.22 micrograms/ml.h. Two-phase elimination pharmacol kinetics were observed for the oral dose, t1/2 for the rapid elimination phase was 3.3 h and for the slow phase 10 h. With the rectal dose tmax was 6 h, Cmax 0.71 +/- 0.44 microgram/ml and AUC0-15 7.58 micrograms/ml.h. The relative rectal bioavailability (AUC rectal/AUC oral) was 49.8%. Elimination rate of the rectal dose was generally slow (t1/2 = 9 h), an observation attributable to the sustained-release effect of the rectal suppository base, PEG 6000. The indication is that the rectal formulation cannot be substituted totally for the oral without first increasing the rectal dose; the 200 mg suppository can however be employed as a follow-up therapy to the oral dose in certain situations.

  9. Oral administration of French maritime pine bark extract (Flavangenol(®)) improves clinical symptoms in photoaged facial skin.

    PubMed

    Furumura, Minao; Sato, Noriko; Kusaba, Nobutaka; Takagaki, Kinya; Nakayama, Juichiro

    2012-01-01

    French maritime pine bark extract (PBE) has gained popularity as a dietary supplement in the treatment of various diseases due to its polyphenol-rich ingredients. Oligometric proanthocyanidins (OPCs), a class of bioflavonoid complexes, are enriched in French maritime PBE and have antioxidant and anti-inflammatory activity. Previous studies have suggested that French maritime PBE helps reduce ultraviolet radiation damage to the skin and may protect human facial skin from symptoms of photoaging. To evaluate the clinical efficacy of French maritime PBE in the improvement of photodamaged facial skin, we conducted a randomized trial of oral supplementation with PBE. One hundred and twelve women with mild to moderate photoaging of the skin were randomized to either a 12-week open trial regimen of 100 mg PBE supplementation once daily or to a parallel-group trial regimen of 40 mg PBE supplementation once daily. A significant decrease in clinical grading of skin photoaging scores was observed in both time courses of 100 mg daily and 40 mg daily PBE supplementation regimens. A significant reduction in the pigmentation of age spots was also demonstrated utilizing skin color measurements. Clinically significant improvement in photodamaged skin could be achieved with PBE. Our findings confirm the efficacy and safety of PBE.

  10. Understanding Adherence to Daily and Intermittent Regimens of Oral HIV Pre-exposure Prophylaxis Among Men Who Have Sex with Men in Kenya.

    PubMed

    Mugo, Peter Mwangi; Sanders, Eduard J; Mutua, Gaudensia; van der Elst, Elisabeth; Anzala, Omu; Barin, Burc; Bangsberg, David R; Priddy, Frances H; Haberer, Jessica E

    2015-05-01

    A qualitative assessment of Kenyan men who have sex with men taking daily and intermittent oral HIV pre-exposure prophylaxis (PrEP) found stigma, sex work, mobility, and alcohol impacted adherence. We analyzed quantitative data from the same cohort to explore different definitions of intermittent adherence. Volunteers were randomized to daily emtricitabine/tenofovir or placebo, or intermittent (prescription: Mondays/Fridays/after sex, maximum 1 dose/day) emtricitabine/tenofovir or placebo (2:1:2:1), and followed for 4 months. By electronic monitoring, median adherence for daily dosing was 80 %. Median adherence for intermittent dosing was 71 % per a "relaxed" definition (accounting for off-prescription dosing) and 40 % per a "strict" definition (limited to the prescription). Factors associated with lower adherence included travel, transactional sex, and longer follow-up; higher adherence was associated with daily dosing and an income. The definition of intermittent dosing strongly affects interpretation of adherence. These findings suggest interventions should address challenges of mobility, sex work, and long-term PrEP.

  11. Acute development of cortical porosity and endosteal naïve bone formation from the daily but not weekly short-term administration of PTH in rabbit

    PubMed Central

    Yamane, Hiroshi; Takakura, Aya; Shimadzu, Yukari; Kodama, Toshiyuki; Lee, Ji-Won; Isogai, Yukihiro; Ishizuya, Toshinori; Takao-Kawabata, Ryoko

    2017-01-01

    Teriparatide [human parathyroid hormone (1–34)], which exerts an anabolic effect on bone, is used for the treatment of osteoporosis in patients who are at a high risk for fracture. That the once-daily administration of teriparatide causes an increase in cortical porosity in animal models and clinical studies has been a matter of concern. However, it is not well documented that the frequency of administration and/or the total dose of teriparatide affect the cortical porosity. The present study developed 4 teriparatide regimens [20 μg/kg/day (D20), 40 μg/kg/day (D40), 140 μg/kg/week (W140) and 280 μg/kg/week (W280)] in the rabbit as a model animal with a well-developed Haversian system and osteons. The total weekly doses were equivalent in the low-dose groups (D20 and W140) and in the high-dose groups (D40 and W280). After the short-term (1 month) administration of TPDT, micro-CT, histomorphometry and three-dimensional second harmonic generation (3D-SHG) imaging to visualize the bone collagen demonstrated that daily regimens but not weekly regimens were associated with the significant development of cortical porosity and endosteal naïve bone formation by marrow fibrosis. We concomitantly monitored the pharmacokinetics of the plasma teriparatide levels as well as the temporal changes in markers of bone formation and resorption. The analyses in the present study suggested that the daily repeated administration of teriparatide causes more deleterious changes in the cortical microarchitecture than the less frequent administration of higher doses. The findings of the present study may have some implications for use of teriparatide in clinical treatment. PMID:28394900

  12. HIV/AIDS-related attitudes and oral impacts on daily performances: a cross-sectional study of Sudanese adult dental patients

    PubMed Central

    2013-01-01

    Background Few studies have investigated the relationships between HIV-related knowledge, fear of contagion in dental environments and Oral Impacts on Daily Performance (OIDP) among dental patients. Our objectives were to investigate the associations between HIV-related knowledge and fear of contagion in dental environments and OIDP among dental patients, and to evaluate whether those associations were modified by the frequency of dental service attendance. Methods A total of 1262 patients (mean age 30.7 years, 56.5% females) were recruited from the Khartoum Dental Teaching Hospital and the University of Science and Technology during March–July 2008. The participants underwent a full-mouth oral clinical examination and completed an interview in a face-to-face setting. Results Of the study participants, 41.4% had visited a dentist at least twice during the last 2 years, 96.2% had caries experience (DT > 0) and 79.1% reported oral impacts (OIDP > 0). The most frequently reported oral impacts were problems eating, sleeping and cleaning teeth. In total, 26.3% of the participants had HIV transmission knowledge, 75.6% knew people with HIV/AIDS and 58.7% perceived a high risk of cross-infection in dental environments. After adjusting for sociodemographic characteristics, frequency of dental service attendance and caries experience, patients who had high HIV-related information exposure, a positive attitude toward people with HIV/AIDS and a high perceived risk of cross-infection were more likely to report oral impacts, whereas patients who knew people with HIV/AIDS were less likely to report oral impacts. The association between OIDP and HIV transmission knowledge was modified by frequency of dental service attendance. Conclusions Dental patients who were informed about HIV and had a high HIV/AIDS risk perception were more likely to report impaired oral health-related quality of life than their less informed counterparts and those who perceived a low risk of

  13. Periodontal status, tooth loss and self-reported periodontal problems effects on oral impacts on daily performances, OIDP, in pregnant women in Uganda: a cross-sectional study

    PubMed Central

    Wandera, Margaret N; Engebretsen, Ingunn M; Rwenyonyi, Charles M; Tumwine, James; Åstrøm, Anne N

    2009-01-01

    Background An important aim of antenatal care is to improve maternal health- and well being of which oral health is an important part. This study aimed to estimate the prevalence of oral impacts on daily performances (OIDP) during pregnancy, using a locally adapted OIDP inventory, and to document how periodontal status, tooth-loss and reported periodontal problems are related to oral impacts. Methods Pregnant women at about 7 months gestational age who were members of a community based multi-center cluster randomized community trial: PROMISE EBF: Safety and Efficacy of Exclusive Breast feeding in the Era of HIV in Sub-Saharan Africa, were recruited in the district of Mbale, Eastern Uganda between January 2006 and June 2008. A total of 877 women (participation rate 877/886, 98%, mean age 25.6, sd 6.4) completed an interview and 713 (participation rate 713/886, 80.6%, mean age 25.5 sd 6.6) were examined clinically with respect to tooth-loss and according to the Community Periodontal Index, CPI. Results Seven of the original 8 OIDP items were translated into the local language. Cronbach's alpha was 0.85 and 0.80 in urban and rural areas, respectively. The prevalence of oral impacts was 25% in the urban and 30% in the rural area. Corresponding estimates for CPI>0 were 63% and 68%. Adjusted ORs for having any oral impact were 1.1 (95% CI 0.7-1.7), 1.9 (95% CI 1.2-3.1), 1.7 (1.1-2.7) and 2.0 (0.9-4.4) if having respectively, CPI>0, at least one tooth lost, tooth loss in molars and tooth loss in molar-and anterior regions. The Adjusted ORs for any oral impact if reporting periodontal problems ranged from 2.7(95% CI 1.8-4.2) (bad breath) through 8.6(95% CI 5.6-12.9) (chewing problem) to 22.3 (95% CI 13.3-35.9) (toothache). Conclusion A substantial proportion of pregnant women experienced oral impacts. The OIDP impacts were most and least substantial regarding functional- and social concerns, respectively. The OIDP varied systematically with tooth loss in the molar region

  14. Hepatic, metabolic and toxicity evaluation of repeated oral administration of SnS2 nanoflowers in mice.

    PubMed

    Bai, Disi; Li, Qingzhao; Xiong, Yanjie; Wang, Chao; Shen, Peijun; Bai, Liyuan; Yuan, Lu; Wu, Ping

    2018-05-02

    Tin sulphide (SnS2) nanoflowers (NFs) with highly photocatalytic activity for wastewater treatment may lead to potential health hazards via oral routes of human exposure. No studies have reported the hepatic effects of SnS2 NFs on the metabolic function and hepatotoxicity. In this study, we examined the hepatic effects of the oral administration of SnS2 NFs (250-1000 mg/kg) to ICR mice for 14 d, with the particle size ranging from 50 to 200 nm. Serum and liver tissue samples were assayed using biochemical analysis, liver histopathology and metabolic gene expression. The different sizes of SnS2 NFs (250 mg/kg dose), such as 50, 80 and 200 nm, did not induce any adverse hepatic effect related to biochemical parameters or histopathology in the treated mice compared with controls. The oral administration of 50-nm SnS2 NFs at doses of 250, 500 and 1000 mg/kg for 14 d produced dose-dependent hepatotoxicity and inflammatory responses in treated mice. Furthermore, the expression of metabolic genes in the liver tissues was altered, supporting the SnS2 NF-related hepatotoxic phenotype. The oral administration of SnS2 NFs also produced abnormal microstructures in the livers of the treated mice. Taken together, these data indicate that the increased risk of hepatotoxicity in SnS2 NF-treated mice was independent of the particle size but was dependent on their dose. The no-observed-adverse effect level was <250 mg/kg for the 50-nm SnS2 NFs. Our study provides an experimental basis for the safe application of SnS2 NFs.

  15. Metabolomic and pharmacokinetic study on the mechanism underlying the lipid-lowering effect of oral-administrated berberine

    PubMed Central

    Gu, Shenghua; Cao, Bei; Sun, Runbin; Tang, Yueqing; Paletta, Janice L.; Wu, Xiao-Lei; Liu, Linsheng; Zha, Weibin; Zhao, Chunyan; Li, Yan; Radlon, Jason M.; Hylemon, Phillip B.; Zhou, Huiping; Aa, Jiye; Wang, Guangji

    2014-01-01

    Clinic and animal studies demonstrated that oral-administrated berberine had distinct lipid-lowering effect. However, pharmacokinetic studies showed berberine was poorly absorbed into the body so that the levels of berberine in the blood and target tissues were far below the effective concentrations revealed. To probe the underlying mechanism, the effect of berberine on biological system was studied on a high-fat-diet-induced hamster hyperlipidemia model. Our results showed that intragastric-administered berberine was poorly absorbed into circulation and most berberine accumulated in gut content. Although the bioavailability for intragastric-administered berberine was much lower than that of intraperitoneal-administered berberine, it had stronger lipid-lowing effect, indicating gastrointestinal is a potential target for hypolipidemic effect of berberine. Metabolomic study on both serum and gut content showed that oral-administrated berberine significantly regulated molecules involved in lipid metabolism, and increased the generation of bile acids in the hyperlipidemic model. DNA analysis revealed that the oral-administered berberine modulated the gut microbiota, and BBR showed a significant inhibition on the 7α-dehydroxylation conversion of cholic acid to deoxycholic acid, indicating a decreased elimination of bile acids in the gut. However, in model hamsters, elevated bile acids failed to down-regulate the expression and function of CYP7A1 in a negative feed-back way. It was suggested that the hypocholesterolemic effect for oral-administrated berberine is involved in its effect on modulating the turnover of bile acids and farnesoid X receptor signal pathway. PMID:25411028

  16. Oral administration of γ-aminobutyric acid affects heat production in a hot environment in resting humans.

    PubMed

    Miyazawa, Taiki; Kawabata, Takashi; Okazaki, Kazunobu; Suzuki, Takashi; Imai, Daiki; Hamamoto, Takeshi; Matsumura, Shinya; Miyagawa, Toshiaki

    2012-02-29

    Central administration of γ-amino butyric acid (GABA) induces lower body temperature in animals in hot ambient air. However, it is still unknown whether oral GABA administration affects temperature regulation at rest in a hot environment in humans. Therefore, in the present study, we specifically hypothesized that systemic administration of GABA in humans would induce hypothermia in a hot environment and that this response would be observed in association with decreased heat production. Eight male participants drank a 200-ml sports drink with 1 g of GABA (trial G) or without GABA (trial C), then rested for 30 minutes in a sitting position in a hot environment (ambient air temperature 33°C, relative humidity 50%). We found that changes in esophageal temperature from before drinking the sports drink were lower in trial G than in trial C (-0.046 ± 0.079°C vs 0.001 ± 0.063°C; P < 0.05), with lower heat production calculated by oxygen consumption (41 ± 5 W/m2 vs 47 ± 8 W/m2; P < 0.05). In this study, we have demonstrated that a single oral administration of GABA induced a larger decrease in body core temperature compared to a control condition during rest in a hot environment and that this response was concomitant with a decrease in total heat production.

  17. Oral administration of Lactobacillus plantarum CJLP133 and CJLP243 alleviates birch pollen-induced allergic rhinitis in mice.

    PubMed

    Choi, S-P; Oh, H-N; Choi, C-Y; Ahn, H; Yun, H S; Chung, Y M; Kim, B; Lee, S J; Chun, T

    2018-03-01

    In this study, we evaluated the therapeutic efficacy of selected probiotics in a mouse model of birch pollen (BP)-induced allergic rhinitis. Oral administration of Lactobacillus plantarum CJLP133 and CJLP243 ameliorated the symptoms of BP-induced allergic rhinitis by reducing airway hyperresponsiveness, and both the histological scores and the number of infiltrated cells in the nasal cavities and lungs. Compared with those from vehicle-treated mice, bronchoalveolar lavage fluid and draining lymph node samples from CJLP133 and CJLP243-administrated mice showed diminished numbers of immune cells, increased secretion of a Th1-type cytokine (IFN-γ) and decreased production of Th2-type cytokines (IL-4, IL-5 and IL-13). Consistent with these results, levels of IL-4, IL-5, IL-13, serum IgE and BP-specific serum IgG1 were decreased, whereas secretion of IFN-γ and BP-specific serum IgG2a was augmented upon administration of CJLP133 and CJLP243 in mice. Oral administration of L. plantarum CJLP133 and CJLP243 alleviates symptoms of BP-induced allergic rhinitis in mice by recovering Th1/Th2 balance via enhancement of the Th1-type immune response. Lactobacillus plantarum CJLP133 and CJLP243 have therapeutic effects on BP-induced allergic rhinitis in an animal model. © 2017 The Society for Applied Microbiology.

  18. Influence of functional dentition on satisfaction with oral health and impacts on daily performance among Brazilian adults: a population-based cross-sectional study.

    PubMed

    Chalub, Loliza Luiz Figueiredo Houri; Ferreira, Raquel Conceição; Vargas, Andréa Maria Duarte

    2017-07-11

    Dental esthetics, chewing and speech should be preserved in a dentition denominated functional and are closely related to satisfaction with oral health (SOH), impacts caused by oral problems and have a possible association with Oral Health-Related Quality of Life. Thus, the purpose of the present study was to investigate the influence of different concepts of functional dentition (FD) on both SOH and impacts on daily performance (IDP) among Brazilian adults. A cross-sectional study was conducted with 9564 adults (35-44 years). SOH and IDP were evaluated using the Oral Impacts on Daily Performance (OIDP) questionnaire. FD was considered based on four different definitions: I-classification of the World Health Organization (FDWHO = ≥20 teeth); II-well-distributed teeth (WDT = ≥10 teeth in each arch); III-classified by esthetics and occlusion (FD Class5  = sequential presence of one tooth in each arch, ≥10 teeth in each arch, 12 anterior teeth, ≥three posterior occluding pairs [POPs] of premolars and ≥one POP molar bilaterally); and IV-classified by esthetics, occlusion and periodontal status (FD Class6  = FD Class5 plus all sextants with CPI ≤ 3 and/or CAL ≤ 1). The proportion of adults satisfied with oral health and without overall impact (OIDP = 0) was calculated for each definition of FD. Multiple Poisson regression models were adjusted by demographic-socioeconomic characteristics, self-reported oral problems and the use of dental services for each dependent variable. When FD Class5 and FD Class6 were considered a greater proportion of adults reported being satisfied (52.1 and 53.1%, respectively) and have OIDP = 0 (52.4 and 53.3, respectively). In the multiple models, SOH was associated with FD Class5 (RP = 1.21) and FD Class6 (RP = 1.24) and OIDP = 0 was associated with WDT (RP = 1.14) and FD Class6 (RP = 1.21). The greater influence of WDT, FD Class5 and FD Class6 on aspects related to quality of life in comparison to

  19. Pharmacokinetics and effect of food after oral administration of prolonged-release tablets of ropinirole hydrochloride in Japanese patients with Parkinson's disease.

    PubMed

    Hattori, N; Hasegawa, K; Sakamoto, T

    2012-10-01

    Ropinirole hydrochloride, a dopamine receptor agonist with a non-ergot alkaloid structure, is highly selective for the dopamine D(2) /D(3) receptors. This study was conducted to evaluate the steady-state pharmacokinetics, safety and efficacy after repeated oral administration of prolonged-release tablets of ropinirole hydrochloride in the absence of L-dopa preparations in Japanese patients with Parkinson's disease (PD). This was a multicenter, open-label, uncontrolled study. The total duration of participation in the study ranged from 56 to 63 weeks. In the study, the plasma concentrations of ropinirole, its major metabolite SK&F104557 (N-depropyl ropinirole) and another metabolite SK&F89124 (ropinirole hydroxylated at the seventh position of the indole ring) were assessed. Safety based on adverse events, haematology, biochemistry, urinalysis and electrocardiography (ECG) (standard 12-lead ECG) were evaluated, and vital signs (blood pressure/pulse rate) were measured. Efficacy based on the Japanese version of Unified Parkinson's Disease Rating Scale (UPDRS) Parts III (motor) and II [activities of daily living (ADL)] as well as tolerability was evaluated. After repeated oral administration of prolonged-release tablets of ropinirole hydrochloride in Japanese patients with PD, ropinirole, SK&F104557 and low levels of SK&F89124 were detected in plasma. The trough concentrations of ropinirole and the two metabolites increased in proportion to the dose when ropinirole hydrochloride prolonged-release tablets were administered at doses ranging from 2 to 16 mg/day. The plasma exposure to ropinirole and its two metabolites after intake of normal diet was comparable to that in the fasting state. The most common adverse events (10% or more) were somnolence, nausea, constipation, hallucination and nasopharyngitis. Most adverse events were mild or moderate in severity, and with no death. During the treatment period, serious adverse events were reported in five patients. Efficacy

  20. Comparative pharmacokinetics of swertiamarin in rats after oral administration of swertiamarin alone, Qing Ye Dan tablets and co-administration of swertiamarin and oleanolic acid.

    PubMed

    Xu, Gui-li; Li, Hong-liang; He, Jian-chang; Feng, En-fu; Shi, Pan-pan; Liu, Yue-qiong; Liu, Chang-xiao

    2013-08-26

    Qing Ye Dan is a well-known herbal drug that is widely used to treat viral hepatitis in the Yi and Hani minority regions in the Yunnan province of China. An LC-MS/MS method was developed to determine the levels of swertiamarin in rat plasma. Swertiamarin and naringin (internal standard, IS) were extracted from rat plasma using solid-phase extraction (SPE) to purify the samples. The pharmacokinetics of the following different administration methods of swertiamarin in rats were studied: oral administration of swertiamarin alone, a Qing Ye Dan tablet (QYDT) and co-administration of swertiamarin and oleanolic acid, with each method delivering approximately 20mg/kg of swertiamarin. Non-compartmental pharmacokinetic profiles were constructed by using the software DAS (version 2.1.1), and the pharmacokinetic parameters were compared using an unpaired Student's t-test. The results showed that the pharmacokinetic parameters Cmax, AUC0-∞, Vz/F and CLz/F were significantly different (P<0.05) among the three types of swertiamarin administration. The data indicate that oleanolic acid and the other ingredients present in QYDT could affect the pharmacokinetic behaviour of swertiamarin in rats. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. The effects of co-administration of butter on the absorption, metabolism and excretion of catechins in rats after oral administration of tea polyphenols.

    PubMed

    Zhang, Liang; Han, Yuhui; Xu, Liwei; Liang, Yuhong; Chen, Xin; Li, Junsong; Wan, Xiaochun

    2015-07-01

    In Southwest China, tea polyphenols are usually utilized by way of butter tea. Tea polyphenols inhibit the absorption and biosynthesis of fatty acids in vivo, but the effects of butter on the pharmacokinetics of tea polyphenols have drawn less concern. A rapid UHPLC-MS/MS method was used to quantitatively determine the catechins in the plasma, feces and bile of rats after the oral administration of tea polyphenol or its combination with butter. In comparison with the single tea polyphenol treatment, the maximum plasma concentrations (Cmax) of the free EGCG, EGC, EC, GCG, GC and ECG significantly decreased after the co-administration of butter. The mean residence times (MRT) of the free EGCG, EGC, EC, GC and ECG were also significantly prolonged. When the plasma samples were treated with β-glucuronidase and arylsulfatase, the pharmacokinetic parameters of the total catechins (free and conjugated forms) were not affected by the co-administration of butter. These results indicated that the total absorption of catechins was not affected by butter, but the metabolism of catechins had been changed. Furthermore, the fecal catechins were significantly increased by butter. The total fecal amount and excretion ratio of all catechins were increased highly. The biliary excretion of EGCG, EGC, EC, GCG and GC was significantly increased by the co-administration of butter. To sum up, the butter changed the metabolism of catechins in vivo by decreasing the plasma concentration of the free catechins but increasing the conjugated catechins.

  2. 77 FR 40069 - Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-06

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0563... Labeled for Human Use; Enforcement Action Dates AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing its intention to take enforcement...

  3. A pharmacokinetic and residual study of sulfadiazine/trimethoprim in mandarin fish (Siniperca chuatsi) with single- and multiple-dose oral administrations.

    PubMed

    Wang, W; Luo, L; Xiao, H; Zhang, R; Deng, Y; Tan, A; Jiang, L

    2016-06-01

    A pharmacokinetic and tissue residue study of sulfadiazine combined with trimethoprim (SDZ/TMP = 5/1) was conducted in Siniperca chuatsi after single- (120 mg/kg) or multiple-dose (an initial dose of 120 mg/kg followed by a 5-day consecutive dose of 60 mg/kg) oral administrations at 28 °C. The absorption half-life (t1/2α ), elimination half-life (t1/2β ), volume of distribution (Vd /F), and the total body clearance (ClB /F) for SDZ and TMP were 4.3 ± 1.7 to 6.3 ± 1.8 h and 2.4 ± 1.0 to 3.9 ± 0.9 h, 25.9 ± 4.5 to 53.0 ± 5.6 h and 11.8 ± 3.5 to 17.1 ± 3.4 h, 2.34 ± 0.78 to 3.67 ± 0.99 L/kg and 0.39 ± 0.01 to 1.33 ± 0.57 L/kg, and 0.03 ± 0.01 to 0.06 ± 0.01 L/kg·h and 0.02 ± 0.01 to 0.05 ± 0.01 L/kg·h, respectively, after the single dose. The elimination half-life (t1/2β ) and mean residue time (MRT) for SDZ and TMP were 68.8 ± 7.8 to 139.8 ± 12.3 h and 34.0 ± 5.5 to 56.1 ± 6.8 h, and 99.3 ± 6.1 to 201.7 ± 11.5 h and 49.1 ± 3.5 to 81.0 ± 5.1 h, respectively, after the multiple-dose administration. The daily oral SDZ/TMP administration might cause a high tissue concentration and long t1/2β , thereby affecting antibacterial activity. The withdrawal time for this oral SDZ/TMP formulation (according to the accepted guidelines in Europe for maximum residue limits, <0.1 mg/kg of tissues for sulfonamides, and <0.05 mg/kg for TMP) should not be <36 days for fish. © 2015 John Wiley & Sons Ltd.

  4. Once-daily administration of intranasal corticosteroids for allergic rhinitis: a comparative review of efficacy, safety, patient preference, and cost.

    PubMed

    Herman, Howard

    2007-01-01

    The aim of this review was to compare the efficacy, safety, patient preference, and cost-effectiveness of once-daily budesonide aqueous nasal spray (BANS), fluticasone propionate nasal spray (FPNS), mometasone furoate nasal spray (MFNS), and triamcinolone aqueous nasal spray (TANS) for treatment of allergic rhinitis (AR) in adult patients. A MEDLINE search (1966 to January 2004) was conducted to identify potentially relevant English language articles. Pertinent abstracts from recent allergy society meetings were identified also. The medical subject heading search terms included were intranasal corticosteroid (INS), nasal steroid, BANS, MFNS, FPNS, or TANS and AR. Selected studies were randomized, controlled, comparison trials of patients with AR treated with once-daily BANS, MFNS, FPNS, or TANS. All four INSs administered once daily were effective and well tolerated in the treatment of AR in adult patients, with similar efficacy and adverse event profiles. No differences were seen between INSs in systemic effects, except for significantly lower overnight urinary cortisol levels in healthy volunteers treated with FPNS compared with placebo. Based on sensory attributes, patients preferred BANS and TANS versus MFNS and FPNS. BANS was associated with more days of treatment per prescription at a lower cost per day for adults compared with the other INSs and is the only INS with a pregnancy category B rating. BANS, FPNS, MFNS, and TANS have similar efficacy and safety profiles. Differences in sensory attributes, documented safety during pregnancy, and cost may contribute to better patient acceptance of one INS versus another and promote better adherence to therapy.

  5. Expression of verocytotoxic Escherichia coli antigens in tobacco seeds and evaluation of gut immunity after oral administration in mouse model.

    PubMed

    Rossi, Luciana; Di Giancamillo, Alessia; Reggi, Serena; Domeneghini, Cinzia; Baldi, Antonella; Sala, Vittorio; Dell'Orto, Vittorio; Coddens, Annelies; Cox, Eric; Fogher, Corrado

    2013-01-01

    Verocytotoxic Escherichia (E.) coli strains are responsible for swine oedema disease, which is an enterotoxaemia that causes economic losses in the pig industry. The production of a vaccine for oral administration in transgenic seeds could be an efficient system to stimulate local immunity. This study was conducted to transform tobacco plants for the seed-specific expression of antigenic proteins from a porcine verocytotoxic E. coli strain. Parameters related to an immunological response and possible adverse effects on the oral administration of obtained tobacco seeds were evaluated in a mouse model. Tobacco was transformed via Agrobacteium tumefaciens with chimeric constructs containing structural parts of the major subunit FedA of the F18 adhesive fimbriae and VT2e B-subunit genes under control of a seed specific GLOB promoter. We showed that the foreign Vt2e-B and F18 genes were stably accumulated in storage tissue by the immunostaining method. In addition, Balb-C mice receiving transgenic tobacco seeds via the oral route showed a significant increase in IgA-positive plasma cell presence in tunica propria when compared to the control group with no observed adverse effects. Our findings encourage future studies focusing on swine for evaluation of the protective effects of transformed tobacco seeds against E. coli infection.

  6. Pharmacokinetics of Caffeine following a Single Administration of Coffee Enema versus Oral Coffee Consumption in Healthy Male Subjects

    PubMed Central

    Tosri, Nisanuch; Rojanasthien, Noppamas; Srichairatanakool, Somdet; Sangdee, Chaichan

    2013-01-01

    The objective of this study was to determine the pharmacokinetics of caffeine after single administration of a coffee enema versus coffee consumed orally in healthy male subjects. The study design was an open-label, randomized two-phase crossover study. Eleven healthy subjects were randomly assigned either to receive 500 mL of coffee enema for 10 minutes or to consume 180 mL of ready-to-drink coffee beverage. After a washout period of at least 10 days, all the subjects were switched to receive the alternate coffee procedure. Blood samples were collected immediately before and at specific time points until 12 hours after coffee administration in each phase. The mean caffeine content in both the coffee solution prepared for the coffee enema and the ready-to-drink coffee beverage was not statistically different. The C max and AUC of caffeine obtained from the coffee enema were about 3.5 times significantly less than those of the coffee consumed orally, despite having slightly but statistically faster T max. The t 1/2 of caffeine obtained following both coffee procedures did not statistically differ. In summary, the relative bioavailability of caffeine obtained from the coffee enema was about 3.5 times significantly less than those of the coffee consumed orally. PMID:23533801

  7. Oral administration of Bifidobacterium breve attenuates UV-induced barrier perturbation and oxidative stress in hairless mice skin.

    PubMed

    Ishii, Yuki; Sugimoto, Saho; Izawa, Naoki; Sone, Toshiro; Chiba, Katsuyoshi; Miyazaki, Kouji

    2014-07-01

    Recent studies have shown that some probiotics affect not only the gut but also the skin. However, the effects of probiotics on ultraviolet (UV)-induced skin damage are poorly understood. In this study, we aim to examine whether oral administration of live Bifidobacterium breve strain Yakult (BBY), a typical probiotic, can attenuate skin barrier perturbation caused by UV and reactive oxygen species (ROS) in hairless mice. The mice were orally supplemented with a vehicle only or BBY once a day for nine successive days. Mouse dorsal skin was irradiated with UV from days 6 to 9. The day after the final irradiation, the transepidermal water loss (TEWL), stratum corneum hydration, and oxidation-related factors of the skin were evaluated. We elucidated that BBY prevented the UV-induced increase in TEWL and decrease in stratum corneum hydration. In addition, BBY significantly suppressed the UV-induced increase in hydrogen peroxide levels, oxidation of proteins and lipids, and xanthine oxidase activity in the skin. Conversely, antioxidant capacity did not change regardless of whether BBY was administered or not. In parameters we evaluated, there was a positive correlation between the increase in TEWL and the oxidation levels of proteins and lipids. Our results suggest that oral administration of BBY attenuates UV-induced barrier perturbation and oxidative stress of the skin, and this antioxidative effect is not attributed to enhancement of antioxidant capacity but to the prevention of ROS generation.

  8. Changes in cytokine and nitric oxide secretion by rat alveolar macrophages after oral administration of bacterial extracts.

    PubMed Central

    Broug-Holub, E; Persoons, J H; Schornagel, K; Kraal, G

    1995-01-01

    Oral administration of the bacterial immunomodulator Broncho-Vaxom (OM-85), a lysate of eight bacteria strains commonly causing respiratory disease, has been shown to enhance the host defence of the respiratory tract. In this study we examined the effect of orally administered (in vivo) OM-85 on stimulus-induced cytokine and nitric oxide secretion by rat alveolar macrophages in vitro. The results show that alveolar macrophages isolated from OM-85-treated rats secreted significantly more nitric oxide, tumour necrosis factor-alpha (TNF-alpha) and IL-1 beta upon in vitro stimulation with lipopolysaccharide (LPS), whereas, in contrast, LPS-induced IL-6 secretion was significantly lower. The observed effects of in vivo OM-85 treatment on stimulus-induced cytokine secretion in vitro are not due to a direct effect of OM-85 on the cells, because in vitro incubation of alveolar macrophages with OM-85 did not result in altered activity, nor did direct intratracheal instillation of OM-85 in the lungs of rats result in altered alveolar macrophage activity in vitro. It is hypothesized that oral administration of OM-85 leads to priming of alveolar macrophages in such a way that immune responses are non-specifically enhanced upon stimulation. The therapeutic action of OM-85 may therefore result from an enhanced clearance of infectious bacteria from the respiratory tract due to increased alveolar macrophage activity. PMID:7648713

  9. Comparison of once-daily versus twice-weekly terbinafine administration for the treatment of canine Malassezia dermatitis - a pilot study.

    PubMed

    Berger, Darren J; Lewis, Thomas P; Schick, Anthea E; Stone, Richard T

    2012-10-01

    Terbinafine, an allylamine antifungal, is used in pulsatile dose regimens for superficial mycoses in human medicine. To compare the clinical efficacy of twice-weekly versus once-daily terbinafine administration to determine whether preliminary proof-of-concept evidence exists for pulsatile administration of terbinafine in the treatment of canine Malassezia dermatitis and to determine whether twice-weekly treatment results in fewer clinical and owner-perceived adverse events. Twenty client-owned dogs with Malassezia dermatitis. In this randomized, single-blinded clinical trial, dogs were randomly assigned to receive terbinafine (30 mg/kg) either once daily for 21 days (n = 10) or once daily on two consecutive days per week for six doses (n = 10). On day 0 and day 21, a mean yeast count was calculated from eight anatomical locations via adhesive tape-strip cytology, clinical lesion scores were assigned to the same locations, and owners assessed pruritus using a visual analog scale. There was no significant difference between treatment groups with respect to the reduction in mean yeast count (P = 0.343) and clinical lesion scores (P = 0.887). Pruritus measured by visual analog scale was significantly decreased in the twice-weekly treatment group compared with the daily treatment group (P = 0.047). Seven of 20 dogs had a clinically measurable or owner-reported adverse event during treatment that included gastrointestinal disturbances, excessive panting and elevated hepatic enzymes, with no significant difference noted between treatment groups. This pilot study indicates that twice-weekly terbinafine administration may be an effective alternative treatment for canine Malassezia dermatitis and merits further investigation. © 2012 The Authors. Veterinary Dermatology © 2012 ESVD and ACVD.

  10. Oral administration of hyaluronan prevents skin dryness and epidermal thickening in ultraviolet irradiated hairless mice.

    PubMed

    Kawada, Chinatsu; Kimura, Mamoru; Masuda, Yasunobu; Nomura, Yoshihiro

    2015-12-01

    Hyaluronan is a component of the extracellular matrix that plays a role in water retention in tissues. In this study, we orally administered hyaluronans of varying molecular weights (300k and less than 10k) repeatedly to hairless mice exposed to ultraviolet (UV) irradiation and examined their effects on the skin of these mice. UV irradiation induces a marked increase in the epidermal thickness of the dorsal skin and a marked decrease in the skin moisture content; however, orally administered hyaluronan, particularly that with a molecular weight of less than 10k, markedly reversed the increase and decrease in the epidermal thickness and skin moisture content, respectively. Furthermore, on analyzing the mice skin, orally administered hyaluronan with a molecular weight of less than 10k increased the levels of the HAS2 gene expression in the skin. Based on these findings, it is assumed that orally administered hyaluronans, with molecular weight of 300k and less than 10k, reversed UV irradiation-induced skin disturbance. In particular, it was considered that the increase in the skin moisture content by orally administered hyaluronan, with a molecular weight of less than 10k, was related to the effect on skin cells. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Pharmacokinetic interaction of enrofloxacin/trimethoprim combination following single-dose intraperitoneal and oral administration in rats.

    PubMed

    Choi, Myung-Jin; Yohannes, Sileshi Belew; Lee, Seung-Jin; Damte, Dereje; Kim, Jong-Choon; Suh, Joo-Won; Park, Seung-Chun

    2014-03-01

    The pharmacokinetic interaction of enrofloxacin and trimethoprim was evaluated after single-dose intraperitoneal or oral co-administration in rats. Plasma concentrations of the two drugs were determined by high-performance liquid chromatography. Following intraperitoneal combination, a significant (P < 0.05) increase in mean values of plasma half-life (t 1/2) and maximum plasma concentration (C max) was observed for enrofloxacin and trimethoprim, respectively. There was a significant (P < 0.05) increase in mean values of area under the plasma drug concentration versus time from time zero to infinity (AUC0-∞) and C max between combined oral doses (10, 30 and 100 mg/kg) of both antibacterial drugs. Also, after oral conjugation a significant difference in mean values of MRT0-∞ was observed between lower (10 mg/kg) and higher (100 mg/kg) doses of both drugs. A significant increase in pharmacokinetic parameters of both drugs in combined intraperitoneal and oral doses indicated pharmacokinetic interaction of enrofloxacin and trimethoprim. Further study is recommended in other species of animals.

  12. Optimization of health-care organization and perceived improvement of patient comfort by switching from intra-venous BU four-times-daily infusions to a once-daily administration scheme in adult hematopoietic stem cell recipients.

    PubMed

    Xhaard, A; Rzepecki, P; Valcarcel, D; Santarone, S; Fürst, S; Serrano, D; De Angelis, G; Krüger, W; Scheid, C

    2014-04-01

    Previous studies have shown an equivalent pharmacokinetic profile between four-times-daily (4QD) and once-daily (QD) administration of intra-venous (IV) BU, without increased toxicity. We assess the impact of a switch in IV BU from a 4QD to a QD schedule, in terms of health-care organization, staff working conditions, quality of care dispensed and perceived patient comfort. Clinicians, nurses and pharmacists from nine allogeneic transplantation units in five European countries were interviewed face to face. Overall perception of QD versus 4QD BU was very positive. Both administration schemes were evaluated to be equally efficaciousZ. QD BU was perceived to be safer and more convenient. Clinicians and nurses perceived that patient comfort was improved, due to fewer complications associated with repeated infusions, and avoiding night infusions associated with stress, anxiety and decreased quality of sleep. Switching from 4QD to QD BU had a significant impact on health-care organization, with a better integration in the overall management and usual timelines in the pharmacies and transplantation units. Time spent to prepare and administer BU was significantly reduced, leading to potential financial savings that merit further assessment and would be of particular interest in the current economic climate.

  13. Restoration of Tear Secretion in a Murine Dry Eye Model by Oral Administration of Palmitoleic Acid.

    PubMed

    Kimura, Yuki; Mori, Daisuke; Imada, Toshihiro; Izuta, Yusuke; Shibuya, Michiko; Sakaguchi, Hisayo; Oonishi, Erina; Okada, Naoko; Matsumoto, Kenji; Tsubota, Kazuo

    2017-04-05

    Sea buckthorn ( Hippophae rhamnoides ) -derived products have traditionally been used as food and medicinal ingredients in Eastern countries. The purpose of this study was to investigate the effect of oral intake of sea buckthorn oil products on tear secretion using a murine dry eye model. Orally administered sea buckthorn pulp oil (not seed oil) restored aqueous tear secretion to its normal value under a dry eye condition. Palmitoleate (C16:1), a fatty acid present in sea buckthorn pulp oil, preserved tear secretion and suppressed inflammatory cytokines in the lacrimal gland to the same extent as that by pulp oil. These results suggest that an oral intake of sea buckthorn pulp oil has a potency to preserve tear secretion capacity in the dry eye state and palmitoleate, its main constituent fatty acid, is an active component of the oil. This effect may enable a potent diet-based treatment for the prevention of dry eye.

  14. Restoration of Tear Secretion in a Murine Dry Eye Model by Oral Administration of Palmitoleic Acid

    PubMed Central

    Nakamura, Shigeru; Kimura, Yuki; Mori, Daisuke; Imada, Toshihiro; Izuta, Yusuke; Shibuya, Michiko; Sakaguchi, Hisayo; Oonishi, Erina; Okada, Naoko; Matsumoto, Kenji; Tsubota, Kazuo

    2017-01-01

    Sea buckthorn (Hippophae rhamnoides)–derived products have traditionally been used as food and medicinal ingredients in Eastern countries. The purpose of this study was to investigate the effect of oral intake of sea buckthorn oil products on tear secretion using a murine dry eye model. Orally administered sea buckthorn pulp oil (not seed oil) restored aqueous tear secretion to its normal value under a dry eye condition. Palmitoleate (C16:1), a fatty acid present in sea buckthorn pulp oil, preserved tear secretion and suppressed inflammatory cytokines in the lacrimal gland to the same extent as that by pulp oil. These results suggest that an oral intake of sea buckthorn pulp oil has a potency to preserve tear secretion capacity in the dry eye state and palmitoleate, its main constituent fatty acid, is an active component of the oil. This effect may enable a potent diet-based treatment for the prevention of dry eye. PMID:28379171

  15. In vitro and in vivo evaluation of self-nanoemulsifying drug delivery systems of cilostazol for oral and parenteral administration.

    PubMed

    Mahmoud, Dina B; Shukr, Marwa H; Bendas, Ehab R

    2014-12-10

    The current investigation was aimed to improve the solubility of poorly soluble drug, cilostazol (CLZ). Self-nanoemulsifying drug delivery system (SNEDDS) composed of oil, surfactant and co-surfactant for both oral and parenteral administration of CLZ was formulated. The components for SNEDDS were identified by solubility studies, and pseudo-ternary phase diagrams were plotted to identify the efficient self-emulsification regions. The optimum formula, composed of Capryol 90 as an oil phase, Cremophor EL as a surfactant, and Transcutol HP as a co-surfactant in a ratio of 19.8:30.5:49.7 by weight, was able to solubilize CLZ 2000 times higher than its solubility in water. This formula was able to form grade "A" nanoemulsion when diluted with water, resulted in emulsification time of 50±1.1 s, particle size of 14.3 nm, PDI of 0.5 and % transmittance was 97.40%±0.65. It showed excellent in vitro dissolution of 93.1% and 81.5% after 5 min in 0.3% sodium lauryl sulphate solution and phosphate buffer pH 6.4, respectively when compared with the marketed tablet formulation and drug suspension as the tablets showed only 44.3% and 9.9% while CLZ suspension showed 33.9% and 8.8% in 0.3% sodium lauryl sulphate solution and phosphate buffer pH 6.4, respectively. It was found to be robust to dilution, thermodynamically stable with low viscosity values of 14.20±0.35 cP. In vivo study revealed significant increase in bioavailability of CLZ in rabbits to 3.94 fold compared with the marketed tablet formulation after oral administration. This formula could be sterilized by autoclaving and did not cause significant hemolysis to human blood which indicates its safety for intravenous administration with a 1.12 fold increase in bioavailability compared with its oral administration. Our study illustrated the potential use of SNEDDS of poorly soluble CLZ orally, and its successful administration of parenterally when required in acute cases of myocardial and cerebral infarction. Copyright

  16. The chronic oral administration of arginine aspartate decreases secretion of IGF-1 and IGFBP-3 in healthy volunteers.

    PubMed

    Blazejewski, Sylvie; Georges, Agnès; Forest, Karelle; Corcuff, Jean-Benoît; Abouelfath, Abdelilah; Girodet, Pierre-Olivier; Kamagate, Mamadou; Jacquet, Alain; Pillet, Odile; Bordenave, Laurence; Moore, Nicholas

    2009-06-01

    To investigate the effect of chronic oral arginine aspartate on the growth hormone (GH), GH-releasing hormone (GHRH), insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) secretions in healthy volunteers. Twenty-three healthy non-athlete volunteer males were administered arginine aspartate (30 g) orally once daily at 21:00 h for 21 consecutive days. Subjects were hospitalized on days 0, 1, 3, 5, 7, 14 and 21 of treatment. At each hospitalization, concentrations of GHRH, GH, IGF-1 and IGFBP-3 were measured over 4 h after arginine aspartate intake. GH, IGF-1 and IGFBP-3 concentrations were also determined over 12 h at days 0, 1 and 21. Compared with day 1, 4 h GH levels dropped at day 5 and subsequently rose to levels not significantly different from initial ones. The latter was substantiated by 12 h GH levels that did not significantly change from days 1 to 21. GHRH levels were not statistically different, although there was a trend in median values that seemed to inversely mirror those of GH. This dynamic over the course of the study for GH and GHRH was accompanied by a general decrease in IGF-1 and IGFBP-3. In healthy volunteers, a chronic oral treatment with 30 g/day arginine aspartate is followed by a decrease in IGF-1 and IGFBP-3 secretions.

  17. Adherence and acceptability in MTN 001: A randomized cross-over trial of daily oral and topical tenofovir for HIV prevention in women

    PubMed Central

    Minnis, Alexandra M.; Gandham, Sharavi; Richardson, Barbra A.; Guddera, Vijayanand; Chen, Beatrice A.; Salata, Robert; Nakabiito, Clemensia; Hoesley, Craig; Justman, Jessica; Soto-Torres, Lydia; Patterson, Karen; Gomez, Kailazarid; Hendrix, Craig

    2012-01-01

    We compared adherence to and acceptability of daily topical and oral formulations of tenofovir (TFV) used as pre-exposure prophylaxis (PrEP) for HIV prevention among women in South Africa, Uganda and the United States. 144 sexually active, HIV-uninfected women participated in a cross-over study of three regimens: oral tablet, vaginal gel, or both. We tested for differences in adherence and evaluated product acceptability. Self-reported adherence for all regimens was high (94%), but serum TFV concentrations indicated only 64% of participants used tablets consistently. Most women in the U.S. (72%) favored tablets over gel; while preferences varied at the African sites (42% preferred gel and 40% tablets). Findings indicate a role for oral and vaginal PrEP formulations and highlight the importance of integrating pharmacokinetics-based adherence assessment in future trials. Biomedical HIV prevention interventions should consider geographic and cultural experience with product formulations, partner involvement, and sexual health benefits that ultimately influence use. PMID:23065145

  18. Suspected adverse reactions to oral administration of a praziquantel-pyrantel combination in captive cheetahs (Acinonyx jubatus).

    PubMed

    Whitehouse-Tedd, Katherine M; Smith, Liesl; Budd, Jane A; Lloyd, Christopher G

    2017-11-15

    OBJECTIVE To characterize adverse reactions to oral administration of a combination of praziquantel and pyrantel embonate or pyrantel pamoate, with or without oxantel embonate, in captive cheetahs (Acinonyx jubatus). DESIGN Retrospective case series and case-control study. ANIMALS 16 captive cheetahs with signs of adverse reaction to oral administration of praziquantel and pyrantel, with or without oxantel embonate (affected group), and 27 cheetahs without such reactions (unaffected group), all from 3 independent facilities. PROCEDURES Medical records and postmortem findings for affected cheetahs were reviewed and compared with those of unaffected animals. Anthelmintic doses administered, age, and sex of cheetahs were compared between groups. RESULTS 3 reactions in affected cheetahs were fatal, whereas the remainder ranged from mild to severe. Postmortem examination failed to reveal any disease processes or conditions to explain the deaths. No differences in anthelmintic dose were identified between affected and unaffected cheetahs for all facilities combined, and no correlation existed between dose and reaction severity. No association with sex was detected, but affected cheetahs were significantly younger than unaffected cheetahs. This difference was not significant after controlling for facility. CONCLUSIONS AND CLINICAL RELEVANCE Cheetahs were concluded to have had an adverse reaction to the praziquantel-pyrantel combination because of temporal proximity of onset of clinical signs to dose administration, similarity of signs to those reported for toxicosis in other species for these drugs, and a lack of other disease process or environmental explanatory factors. A highly cautious approach to the use of this drug combination is recommended for cheetahs.

  19. Computer versus lecture: a comparison of two methods of teaching oral medication administration in a nursing skills laboratory.

    PubMed

    Jeffries, P R

    2001-10-01

    The purpose of this study was to compare the effectiveness of both an interactive, multimedia CD-ROM and a traditional lecture for teaching oral medication administration to nursing students. A randomized pretest/posttest experimental design was used. Forty-two junior baccalaureate nursing students beginning their fundamentals nursing course were recruited for this study at a large university in the midwestern United States. The students ranged in age from 19 to 45. Seventy-three percent reported having average computer skills and experience, while 15% reported poor to below average skills. Two methods were compared for teaching oral medication administration--a scripted lecture with black and white overhead transparencies, in addition to an 18-minute videotape on medication administration, and an interactive, multimedia CD-ROM program, covering the same content. There were no significant (p < .05) baseline differences between the computer and lecture groups by education or computer skills. Results showed significant differences between the two groups in cognitive gains and student satisfaction (p = .01), with the computer group demonstrating higher student satisfaction and more cognitive gains than the lecture group. The groups were similar in their ability to demonstrate the skill correctly. Importantly, time on task using the CD-ROM was less, with 96% of the learners completing the program in 2 hours or less, compared to 3 hours of class time for the lecture group.

  20. Human urinary excretion profile after smoking and oral administration of ( sup 14 C)delta 1-tetrahydrocannabinol

    SciTech Connect

    Johansson, E.; Gillespie, H.K.; Halldin, M.M.

    The urinary excretion profiles of delta 1-tetrahydrocannabinol (delta 1-THC) metabolites have been evaluated in two chronic and two naive marijuana users after smoking and oral administration of ({sup 14}C)delta 1-THC. Urine was collected for five days after each administration route and analyzed for total delta 1-THC metabolites by radioactivity determination, for delta 1-THC-7-oic acid by high-performance liquid chromatography, and for cross-reacting cannabinoids by the EMIT d.a.u. cannabinoid assay. The average urinary excretion half-life of {sup 14}C-labeled delta 1-THC metabolites was calculated to be 18.2 +/- 4.9 h (+/- SD). The excretion profiles of delta 1-THC-7-oic acid and EMIT readings weremore » similar to the excretion profile of {sup 14}C-labeled metabolites in the naive users. However, in the chronic users the excretion profiles of delta 1-THC-7-oic acid and EMIT readings did not resemble the radioactive excretion due to the heavy influence from previous Cannabis use. Between 8-14% of the radioactive dose was recovered in the urine in both user groups after oral administration. Lower urinary recovery was obtained both in the chronic and naive users after smoking--5 and 2%, respectively.« less

  1. The effects of concurrent administration of cytochrome P-450 inhibitors on the pharmacokinetics of oral methadone in healthy dogs.

    PubMed

    Kukanich, Butch; Kukanich, Kate S; Rodriguez, Jessica R

    2011-05-01

    The objective was to examine the effects of inhibiting cytochrome P450 (CYP) on the pharmacokinetics of oral methadone in dogs. Prospective non-randomized experimental trial. Six healthy Greyhounds (three male and three female). The study was divided into two phases. Oral methadone (mean = 2.1 mg kg(-1) PO) was administered as whole tablets in Phase 1. In Phase 2 oral methadone (2.1 mg kg(-1) PO) was administered concurrently with ketoconazole (13.0 mg kg(-1) PO q 24 hours), chloramphenicol (48.7 mg kg(-1) PO q 12 hours), fluoxetine (1.3 mg kg(-1) PO q 24 hours), and trimethoprim (6.5 mg kg(-1) PO q 24 hours). Blood was obtained for analysis of methadone plasma concentrations by liquid chromatography with mass spectrometry. The maximum plasma concentration (C(max)), time to C(max) (T(max)), and the area under the curve from time 0 to the last measurable time point above the limit of quantification of the analytical assay (AUC(0-LAST)) were compared statistically. The C(max) of methadone was significantly different (p=0.016) for Phase 1 (5.5 ng mL(-1)) and Phase 2 (171.9 ng mL(-1)). The AUC(0-LAST) was also significantly different (p=0.004) for Phase 1 (13.1 hour ng mL(-1)) and Phase 2 (3075.2 hour ng mL(-1)). Concurrent administration of CYP inhibitors with methadone significantly increased the area under the curve and plasma concentrations of methadone after oral administration to dogs. Further studies are needed assessing more clinically relevant combinations of methadone and CYP inhibitors. © 2011 The Authors. Veterinary Anaesthesia and Analgesia © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

  2. Pharmacokinetics of amino acid ester prodrugs of Acyclovir after oral administration: Interaction with the transporters on Caco-2 cells

    PubMed Central

    Katragadda, Suresh; Jain, Ritesh; Kwatra, Deep; Hariharan, Sudharshan; Mitra, Ashim K.

    2008-01-01

    In vivo systemic absorption of the amino acid prodrugs of acyclovir (ACV) after oral administration was evaluated in rats. Stability of the prodrugs, L-Alanine-ACV (AACV), L-Serine-ACV (SACV), L-Isoleucine-ACV (IACV), γ-Glutamate-ACV (EACV) and L-Valine-ACV (VACV) was evaluated in various tissues. Interaction of these prodrugs with the transporters on Caco-2 cells was studied. In vivo systemic bioavailability of these prodrugs upon oral administration was evaluated in jugular vein cannulated rats. The amino acid ester prodrugs showed affinity towards various amino acid transporters as well as the peptide transporter on the Caco-2 cells. In terms of stability, EACV was most enzymatically stable compared to other prodrugs especially in liver homogenate. In oral absorption studies, ACV and AACV showed high terminal elimination rate constants (λz). SACV and VACV exhibited approximately five fold increase in area under the curve (AUC) values relative to ACV (p<0.05). Cmax(T) (maximum concentration) of SACV was observed to be 39 ± 22 µM in plasma which is 2 times better than VACV and 15 times better than ACV. Clast(T) (concentration at the last time point) of SACV was observed to be 0.18 ± 0.06 µM in plasma which is 2 times better than VACV and 3 times better than ACV. Amino acid ester prodrugs of ACV were absorbed at varying amounts (Cmax) and eliminated at varying rates (λz) thereby leading to varying extents (AUC). The amino acid ester prodrug SACV owing to its enhanced stability, higher AUC and better concentration at last time point seems to be a promising candidate for the oral treatment of herpes infections. PMID:18638532

  3. Vitamin D in newborns. A randomised controlled trial comparing daily and single oral bolus vitamin D in infants.

    PubMed

    Huynh, Julie; Lu, Thao; Liew, Danny; Doery, James Cg; Tudball, Ronald; Jona, Madeleine; Bhamjee, Roisin; Rodda, Christine P

    2017-02-01

    There are no published data to demonstrate the efficacy of bolus dose vitamin D in newborn infants. The study sought to evaluate this alternative approach of supplementation. This single centre, open randomised controlled trial was conducted from August 2013 to May 2014. It compared the efficacy and safety of daily (400 IU) versus a bolus dose (50 000 IU) of cholecalciferol in newborn infants of vitamin D deficient mothers. The primary outcome measure was the rate of 25 hydroxyvitamin D (25OHD) repletion-defined as 25OHD greater than 50 nmol/L. The secondary objective was determining safety using adjusted total serum calcium. Of 70 eligible infants, 36 received a daily dose and 34 received a single high-dose cholecalciferol. Mean 25OHD in the bolus group (154 nmol/L, 95% confidence interval (CI) 131-177) was higher than the daily group (48 nmol/L, 95% CI 42-54) at 1-2 weeks of age. This was reversed at 3-4 months, (65 nmol/L, 95% CI 59-71) compared with the daily group (81 nmol/L, 95% CI 77-85). More infants in the single bolus group achieved vitamin D repletion (100 vs. 31%) at 1-2 weeks. By 3-4 months, both groups achieved similar vitamin D repletion rates (91 vs. 89%). Mean adjusted total serum calcium in the bolus group were normal at 1-2 weeks (2.73 mmol/L) and 3-4 months (2.55 mmol/L). Single bolus dosing of 50 000 IU cholecalciferol achieves higher 25OHD repletion rates at 1-2 weeks of age compared with daily dosing, but repletion rates were similar by 3-4 months. There was no hypercalcaemia documented with single bolus dosing in this study. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  4. Long-term maintenance combination chemotherapy with OPEC/MPEC (vincristine or methotrexate, prednisolone, etoposide and cyclophosphamide) or with daily oral etoposide and prednisolone can improve survival and quality of life in adult T-cell leukemia/lymphoma.

    PubMed

    Matsushita, K; Matsumoto, T; Ohtsubo, H; Fujiwara, H; Imamura, N; Hidaka, S; Kukita, T; Tei, C; Matsumoto, M; Arima, N

    1999-12-01

    Acute leukemia and lymphoma varieties of adult T-cell leukemia/lymphoma (ATL) usually carry a poor prognosis. While etoposide is generally useful for treating ATL, especially as a daily oral maintenance regimen, etoposide has not proven effective in severe types of ATL efficient in some patients. Of 87 ATL patients whom we have treated, 51 had acute leukemia, 22 lymphoma and 14 progressive chronic leukemia. Seventy-nine patients were treated with a long term maintenance combination protocol, OPEC/MPEC (weekly doses of vincristine, 0.7 mg/m2 or methotrexate, 14 mg/m2; prednisolone, 20 mg/m2; etoposide, 70 mg/m2 and cyclophosphamide, 200 mg/m2). The other 8 patients, 3 with acute leukemia, 2 with lymphoma and 3 with progressive chronic leukemia, were treated with daily oral administration of 25 mg of etoposide and 10 mg of prednisolone (DOEP). The dose administered was modified in individual cases to maintain the granulocyte count and reduce the number of ATL cells. Considering both protocols, a complete response and a partial response were achieved in 31.0% and 58.6% patients, respectively. Median survival times (MST) of all patients and, acute leukemia, lymphoma and progressive chronic leukemia types were 7.5, 6.7, 9.6 and 12.4 months, respectively. Respective MST of patients treated with OPEC/MPEC or DOEP protocols were 7.1 and 18.0 months. Relatively normal WBC counts, lower lactate dehydrogenase concentration and normal calcium concentration, limited numbers of anatomic sites involved, good performance status and good response to chemotherapy were significantly associated with long survival time. Drug toxicity was not apparent, and about half of patients were treated in an outpatient setting.

  5. [Variations in hyperbilirrubinemia in low birth weight newborns under phototherapy and continous or discontinous agar oral administration (author's transl)].

    PubMed

    Colomer, J; Moya, M; Marco, V; De Paredes, C; Escrivá, F; Vila, R

    1975-06-01

    Therapeutic attitude in hyperbilirrubinemia is always worth because other infrequent complications but not for this, less important. Phototherapy innocuousness, largely demonstrated, fosters its profilactic use at beginning and not only for those babies with serum bilirrubin over 10 mg % in the first day of life. Previously we have reported positive results with agar oral administration without collateral effects. On this grounds we have planned the following experience in a homogenous group of L.B.W.: one group was fed with agar previously to each formula administration; other group received the same amount of agar but divided in only three administrations in 24 hours; the last group received continuous phototherapy for 96 hours with a white cold fluorescent light from a source of 8-Vita-lite lamp of 40 watts with a intensity of 500 foot candle and 30 lumens. All of these babies weighed less than 2.500 g. and were between 10 and 90 percentil of Lubschenko diagram. They were fed with the same formula and same time table with no infusions, rejecting all that presented any type of pathology. Obstetric conditions were basically identical. This population was randomly divided in four groups. 1) Control group with no profilaxis, but with identical bilirrubin andhematocrit determinations. 2) Group with continuous agar oral administration, 125 mg. before each of the seven formula feeding. 3) Group with discontinuous agar administration, 250 mg. before three of the seven formula feeding. 4) Group with continuous phototherapy for 96 hours. These is initial identification of the groups with statistic signification, and after that a quantitative and sequential evolution of bilirrubin is analized in each group.

  6. Pharmacokinetics and dosimetry of the anti-androgen vinclozolin after oral administration inthe rat

    EPA Science Inventory

    Vinclozolin (V) is a fungicide with antiandrogenic properties. To determine the pharmacokinetics and dosimetry of V, adult male rats were administered an oral dose of V (100 mg/kg) in corn oil and sacrificed over time after dosing. V and its metabolites were analyzed in serum and...

  7. Subjective and physiological effects after controlled Sativex and oral THC administration.

    PubMed

    Karschner, E L; Darwin, W D; McMahon, R P; Liu, F; Wright, S; Goodwin, R S; Huestis, M A

    2011-03-01

    Sativex is a cannabis-plant extract delivering nearly 1:1 Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) by oromucosal spray. It has been suggested that CBD attenuates THC-induced tachycardia, anxiety, and euphoria. In this study, pharmacodynamic effects were compared over 10.5 h in nine cannabis smokers randomly assigned to receive placebo, 5 and 15 mg oral synthetic THC, and low (5.4 mg THC, 5.0 mg CBD) and high (16.2 mg THC, 15.0 mg CBD) doses of Sativex. At therapeutic doses, no substantial CBD-induced modulation of THC's effects was evident. Oral THC and Sativex produced similar, clinically insignificant increases in heart rate, anxiety, and "good drug effects" with no serious adverse events. Oral and oromucosal THC have slower absorption, lower rate of THC delivery to the brain, and fewer associated adverse events as compared with smoked cannabis. These results indicate that Sativex has a pharmacodynamic safety profile comparable to that of oral THC at low, therapeutic doses.

  8. Subjective and Physiological Effects After Controlled Sativex and Oral THC Administration

    PubMed Central