Determination of pharmacokinetic parameters of stavudine in Japanese patients infected with HIV-1, using a Gaussian-like input rate function.

We sought to examine variation in pharmacokinetic parameters of stavudine in Japanese patients infected with HIV-1. Stavudine concentrations were measured in two hemophiliacs (HIV-1 asymptomatic carriers (ACs)) and two non-hemophiliacs (both ACs). To simulate the plasma stavudine concentrations following a single oral dose, we used a Gaussian-like input rate function in a single compartment model. The theoretical equation successfully simulated changes in the time course of plasma stavudine concentrations in all four patients. The mean+/-SD of Tmax, Cmax, AUC0-infinity, and t 1/2 were 0.96+/-0.26 hr, 478+/-90 ng/mL, 1112+/-136 ng x hr/mL, and 1.26+/-0.23 hr, respectively. Pharmacokinetic characteristics were comparable to those reported in the literature, although the mean of Cmax was slightly lower and means of Tmax and t 1/2 slightly longer than those previously reported. Interpatient variability in plasma stavudine concentrations was not as dramatic as that seen with lamivudine. Thus, we confirmed the validity of the uniform therapeutic regimen of stavudine in Japanese people with HIV-1 infection.