TY - JOUR
T1 - Steady state bioequivalence of generic and innovator formulations of stavudine, lamivudine, and nevirapine in HIV-infected Ugandan adults
AU - Byakika-Tusiime, Jayne
AU - Chinn, Leslie W.
AU - Oyugi, Jessica H.
AU - Obua, Celestino
AU - Bangsberg, David R.
AU - Kroetz, Deanna L.
PY - 2008/12/19
Y1 - 2008/12/19
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0003981
DO - 10.1371/journal.pone.0003981
M3 - Article
C2 - 19096711
AN - SCOPUS:58049204452
SN - 1932-6203
VL - 3
JO - PloS one
JF - PloS one
IS - 12
M1 - e3981
ER -