The pharmacokinetics of 150 mg lamivudine, 300 mg zidovudine, and 200 mg nevirapine were assessed following single oral administration of a fixed-dose combination tablet and coadministration of the separate innovator products in healthy male subjects (n = 64) under fasting conditions in an open-label, randomized, 2-way crossover study. Multiple blood samples were collected up to 72 hours and plasma concentrations of antiretrovirals were assayed using liquid chromatography/tandem mass spectrometry methods. Pharmacokinetic parameters were calculated using noncompartmental methods, and bioequivalence was assessed using an analysis of variance model. The ratio of the least squares mean (fixed-dose combination to individual products) and 90% confidence intervals of AUC(0-t), AUC(0-infinity), and C(max) for lamivudine, zidovudine, and nevirapine were all within 80.0% to 125.0%, suggesting a similar rate and extent of antiretroviral exposure in the bloodstream. Mean oral clearance (CL/F) values of lamivudine, zidovudine, and nevirapine for the fixed-dose combination were 23.7, 127, and 1.65 L/h, respectively. The fixed-dose combination and individual products were equally safe and well tolerated, with only a few subjects experiencing drug-related adverse events. The current fixed-dose combination of lamivudine, zidovudine, and nevirapine is expected to provide a similar efficacy/safety profile as coadministration of the individual products, a better adherence to treatment, and considerable cost savings in the treatment of HIV.
The bioequivalence of tacrolimus (CAS 104987-11-3) 5 mg capsules was assessed in two single-dose, open-label, randomIzed 2-way crossover trials with a minimum washout period of 14 days; one trial was conducted under fasting condition (n = 44) and the other one under fed condition (n = 48). Blood samples were collected over a 120-h period and concentrations were assayed using a liquid chromatography tandem mass spectrometry (LCMS/MS) method. A non-compartmental method was used for calculation of pharmacokinetic parameters. Under fasting conditions, mean AUC(0-t), AUC(0-inf) and C(max) were comparable between the test (296 ng x h/mL, 318 ng x h/mL and 32 ng/ mL, respectively) and the reference formulations (289 ng x h/mL, 309 ng x h/mL and 33 ng/mL, respectively). T(max) was reached between 1.5 and 2 h post-dose. Mean AUC(0-t), AUC(0-inf) and C(max) were also comparable under fed conditions (154 ng x h/mL, 169 ng x h/mL and 7.6 ng/mL, respectively, for the test and 161 ng x h/mL, 176 ng x h/mL and 7.5 ng/mL, respectively, for the reference formulation). Under fed conditions, T(max) was reached between 5 and 6 h post-dose. 90% geometric confidence intervals were all within the acceptable 80-125% limit, suggesting bioequivalence between the generic product and the innovator product.
The aim of this study is to compare the single-dose oral bioavailability of memantine hydrochloride 10 mg tablets of Ranbaxy Laboratories Limited, with NAMENDA™ tablets (containing memantine hydrochloride 10 mg) of Forest Pharmaceuticals Inc. in healthy, adult, human subjects under fasting condition. The study was carried out as 2-way crossover design on 8 subjects in fasting and fed conditions. The plasma samples were obtained over a 72 h post dose in each period. Plasma memantine samples were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) with positive ion electro spray ionization using multiple reactions monitoring (MRM). A sensitive, reproducible, accurate and validated LC-MS/MS method with limit of quantification (LOQ) 0.200 ng/mL was used to analyze memantine. Ln transformed AUC0-72and Cmaxwere assessed for bioequivalence using 90% confidence interval (CI). 90% confidence intervals for the ratio of test and reference (Ratio of least-squares mean) for ln-transformed AUC0-72and Cmaxwere within the regulatory acceptance criteria of 80-125%.
A bioequivalence study for venlafaxine generic formulation was conducted as an open label, balanced, randomized, two-way crossover, single-dose study. In this study, a comparison of various pharmacokinetic parameters of venlafaxine hydrochloride 150 mg modified release capsules of Ranbaxy and EFEXOR®-XR 150 mg capsules of Wyeth, in healthy, adult, male, human subjects under fasting condition was performed to conclude bioequivalence. Venlafaxine and its major active metabolite O-desmethylvenlafaxine (ODV) are racemates. The "(S)-(+)" and "(R)-(-)" enantiomers of venlafaxine and ODV are established as being active. Hence, subject samples were analyzed using nonstereoselective and stereoselective assay methods. Both (S)-(+) and (R)-(-) enantiomers of venlafaxine and ODV showed similar absorption and disposition. The 90% confidence intervals for venlafaxine, (R)-(-)-venlafaxine as well as (S)-(+)-venlafaxine were within acceptance range concluding bioequivalence. The results obtained by stereoselective assay were comparable to the nonstereoselective analysis, as sum of concentrations of (S)-(+)- and (R)-(-)-enantiomers of venlafaxine and ODV. The mean (S)-(+)/(R)-(-) ratios of the enantiomers of venlafaxine and ODV at various time points were consistent in the study subjects. Therefore, the estimation of venlafaxine and ODV using nonstereoselective assay method is effective in distinguishing formulation differences (if any) in bioequivalence studies in a cost-effective manner.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.