Steady State Bioequivalence of Generic and Innovator Formulations of Stavudine, Lamivudine, and Nevirapine in HIV-Infected Ugandan Adults

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From: PLoS ONE(Vol. 3, Issue 12)
Publisher: Public Library of Science
Document Type: Clinical report
Length: 4,575 words
Lexile Measure: 1400L

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Abstract :

Background Generic antiretroviral therapy is the mainstay of HIV treatment in resource-limited settings, yet there is little evidence confirming the bioequivalence of generic and brand name formulations. We compared the steady-state pharmacokinetics of lamivudine, stavudine and nevirapine in HIV-infected subjects who were receiving a generic formulation (Triomune®) or the corresponding brand formulations (Epivir®, Zerit®, and Viramune®). Methodology/Principal Findings An open-label, randomized, crossover study was carried out in 18 HIV-infected Ugandan subjects stabilized on Triomune-40. Subjects received lamivudine (150 mg), stavudine (40 mg), and nevirapine (200 mg) in either the generic or brand formulation twice a day for 30 days, before switching to the other formulation. At the end of each treatment period, blood samples were collected over 12 h for pharmacokinetic analysis. The main outcome measures were the mean AUC.sub.0-12h and C.sub.max . Bioequivalence was defined as a geometric mean ratio between the generic and brand name within the 90% confidence interval of 0.8-1.25. The geometric mean ratios and the 90% confidence intervals were: stavudine C.sub.max, 1.3 (0.99-1.71) and AUC.sub.0-12h, 1.1 (0.87-1.38); lamivudine C.sub.max, 0.8 (0.63-0.98) and AUC.sub.0-12h, 0.8 (0.65-0.99); and nevirapine C.sub.max, 1.1 (0.95-1.23) and AUC.sub.0-12h, 1.1 (0.95-1.31). The generic formulation was not statistically bioequivalent to the brand formulations during steady state, although exposures were comparable. A mixed random effects model identified about 50% intersubject variability in the pharmacokinetic parameters. Conclusions/Significant Findings These findings provide support for the use of Triomune in resource-limited settings, although identification of the sources of intersubject variability in these populations is critical.

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Gale Document Number: GALE|A472536078