Abstract
BackgroundGeneric 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 FindingsAn 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 FindingsThese 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.
Highlights
Generic drugs provide patients with lower-cost alternatives to the more costly brand name drugs
Two subjects were excluded from the analysis because their plasma samples were not sufficient for pharmacokinetic analysis
One exception is that in the former study, the generic Triomune formulation resulted in a significant increase in stavudine Cmax compared to the brand name
Summary
Generic drugs provide patients with lower-cost alternatives to the more costly brand name drugs. The use of generics has resulted in substantial savings to consumers and governments These drugs have dramatically reduced the morbidity and mortality due to HIV/AIDS, and drug quality is a key factor in attaining the long term goals of sustained viral suppression with minimal drug resistance. Drug pharmacokinetics and pharmacodynamics may vary in ethnically distinct populations of HIV-infected patients. Since this is chronic therapy, there is a need to evaluate the steady-state pharmacokinetics of these drugs in the target population. We compared the steady-state pharmacokinetics of lamivudine, stavudine and nevirapine in HIV-infected subjects who were receiving a generic formulation (TriomuneH) or the corresponding brand formulations (EpivirH, ZeritH, and ViramuneH)
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