Nevirapine/lamivudine/stavudine as a combined-formulation tablet: bioequivalence study compared with each component administered concurrently under fasting condition.
OBJECTIVE
The objective of the study was to compare the bioequivalence of a fixed-dose combination of a nevirapine 200 mg, lamivudine 150 mg and stavudine 30 mg combination tablet with application of the 3 medications, at the same dosage, concurrently as separate formulations, in healthy, adult subjects under fasting conditions.


METHODS
An open-label, balanced, randomized, 2-treatment, 2-period, 2-sequence, single-dose, crossover bioavailability study was conducted in 40 subjects with 21-day washout period between each treatment. Blood samples were collected for 168 hours. Plasma concentrations of nevirapine, lamivudine and stavudine were determined using a validated LC-MS-MS method. Noncompartmental pharmacokinetics and statistical analyses were performed using SAS (SAS Institute Inc., Cary, NC, USA) software (SAS System under Windows, Version 8.02).


RESULTS
The ratios of least-square means and the 90% confidence intervals of the log-transformed data were calculated for AUC(0-t), AUC(0-inf), and Cmax. The 90% confidence interval for least-square mean ratio between test and reference formulation for log-transformed parameters Cmax, AUC(0-t) and AUC(0-inf) were within the requirements of the 80-125% range.


CONCLUSIONS
The test formulation (Ranbaxy Laboratories Ltd., Gurgaon, India) is bioequivalent to the reference formulations both in terms of rate and extent of absorption after single-dose administration under fasting condition.
Monif
T
T
Department of Clinical Pharmacology and Pharmacokinetics, Ranbaxy Laboratories Ltd., Gurgaon, Haryana, India. tausif.monif@ranbaxy.com
Tippabhotla
S K
SK
Garg
M
M
Singla
A K
AK
Vijan
T
T
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D018119:Stavudine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency
D019380:Anti-HIV Agents; D004338:Drug Combinations; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine