Pharmacokinetics of nevirapine and lamivudine in patients with HIV-1 infection.

The purpose of this parallel treatment group, double-blind, multicenter study was to characterize the pharmacokinetics of nevirapine and lamivudine when coadministered to patients with the HIV-1 infection. This pharmacokinetic interaction study was nested within a larger Phase III clinical trial conducted to characterize the safety and efficacy of coadministered nevirapine and lamivudine. One hundred HIV-1 infected patients with CD4+ lymphocyte counts < 200 cells/mm3and who were on a background of nucleoside (zidovudine [ZDV], didanosine [ddI], zalcitabine [ddC], stavudine [d4T]) therapy were randomly assigned to be treated with either nucleoside + lamivudine + nevirapine or nucleoside + lamivudine + placebo. Each patient underwent blood sampling at defined times for the purpose of determining the concentration of nevirapine in plasma and lamivudine in serum under steady-state conditions. Each patient was also monitored closely for concomitant administration of other drugs, including ZDV, ddI, ddC, d4T and cotrimoxazole. The pharmacokinetics of nevirapine and lamivudine were characterized using nonlinear mixed-effects modeling. There were no reported serious adverse events during the 40-day pharmacokinetic study. The results of the modeling analysis revealed that nevirapine had no effect on the pharmacokinetics of lamivudine. Estimates of the apparent clearance for nevirapine (CL/F = 3.3 L/hour; 95% confidence interval [CI] 2.9 to 3.7 L/hour) and lamivudine (CL/F 27.6 L/hour; 95% CI 22 to 33.2 L/hour) were consistent with the values reported in earlier trials. However, the results also showed that concomitant administration of lamivudine with cotrimoxazole resulted in a 31% reduction in the apparent clearance of lamivudine, resulting in a 43% increase in the average steady-state lamivudine serum concentrations. These results indicate that chronic concurrent administration of cotrimoxazole with lamivudine may significantly affect the steady-state pharmacokinetics of lamivudine.

RCT Entities:   Population Interventions Outcomes