Comparative bioavailability/bioequivalence of two different stavudine 40 mg capsule formulations: a randomized, 2-way, crossover study in healthy volunteers under fasting condition.

PURPOSE: The aim of this study was to compare the single-dose oral bioavailability of two formulations of stavudine 40 mg capsules in healthy human subjects.

METHODS: A bioequivalence study of two oral capsule formulations of 40 mg stavudine was carried out in 40 healthy volunteers following a single-dose, 2-sequence, crossover and randomized design. The two formulations were stavudine 40 mg capsules (Ranbaxy Laboratories Ltd., Haryana, India) as test and zerit 40 mg capsules (Bristol-Myers Squibb, Princeton, NJ, USA) as reference product. Test and reference capsules were administered to each subject in each period separated by a 3-day washout period. Serial blood samples were collected for a period of 10 h. Blood plasma was analyzed for stavudine using a sensitive, reproducible, accurate and validated LC-MS/MS method. Pharmacokinetic parameters, including AUC(0-t), AUC(0-inf), C(max), t(max), t(1/2) and lambda(z), were determined from plasma concentrations for both formulations. AUC(0-t), AUC(0-inf) and C(max) were tested for bioequivalence after log-transformation of data.

RESULTS: The LC-MS/MS method, used to quantify stavudine in human plasma, was specific and sensitive for stavudine. Plasma concentration profiles of stavudine test and reference treatments were similar. Geometric mean ratios and 90% confidence intervals for C(max), AUC(0-t) and AUC(0-inf) for stavudine were 99.9 (93.9-106), 99.9 (98.4-101) and 99.8 (98.2-101), respectively. Untransformed results for the same parameters were consistent with the natural log-transformed data.

CONCLUSION: The two stavudine 40 mg capsule formulations examined were bioequivalent and may be used interchangeably in medical practice.