Steady state bioequivalence of generic and innovator formulations of stavudine, lamivudine, and nevirapine in HIV-infected Ugandan adults

Jayne Byakika-Tusiime, Leslie W. Chinn, Jessica H. Oyugi, Celestino Obua, David R. Bangsberg, Deanna L. Kroetz

Research output: Contribution to journalArticle

9 Scopus citations

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 AUC0-12h and Cmax. 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 Cmax, 1.3 (0.99-1.71) and AUC0-12h, 1.1 (0.87-1.38); lamivudine Cmax, 0.8 (0.63-0.98) and AUC0-12h, 0.8 (0.65-0.99); and nevirapine Cmax, 1.1 (0.95-1.23) and AUC0-12h, 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.

Original languageEnglish (US)
Article numbere3981
JournalPloS one
Volume3
Issue number12
DOIs
StatePublished - Dec 19 2008

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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