چکیده (انگلیسی):

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/mm3 and 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 mixedeffects
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.