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


CONCLUSIONS
The two stavudine 40 mg capsule formulations examined were bioequivalent and may be used interchangeably in medical practice.
Monif
T
T
Department of Clinical Pharmacology and Pharmacokinetics, Ranbaxy Laboratories, Gurgaon, Haryana, India. tausif.monif@ranbaxy.com
Tippabhotla
S K
SK
Garg
M
M
Singla
A K
AK
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D006801:Humans; D013058:Mass Spectrometry; D018119:Stavudine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency
D019380:Anti-HIV Agents; D002214:Capsules; D018119:Stavudine