Pharmacokinetic consideration on administration regimen of lamivudine in Japanese patients infected with HIV-1

Objective: The typical regimen for lamivudine is 150 mg bis in die (bid). H owever, pharmacokinetic values of lamivudine will differ among individual p atients. In addition, few studies regarding the pharmacokinetics of lamivud ine in the Japanese people have so far been reported. Therefore, we have ai med to examine the variation in the pharmacokinetic values of lamiduvine pr esent in six Japanese patients with HIV-I infection. Patients and methods: Lamivudine concentrations were measured in three hemophiliacs (HIV-l-asympt omatic carrier, AC) and three non-hemophiliacs (2 of these patients were AC and one had AIDS-related complex, ARC). In order to simulate the lamivudin e plasma concentrations found in chronic oral administration, we added an a bsorption compartment to the two-compartment model. Results: The mean +/- S D of T-max C-max, AUC(0-infinity), and t(1/2)beta were 1.2 +/- 0.5 (hours), 1280 +/- 267 (ng/ml), 6778 +/- 2763 (ngxh/ml), and 10.3 +/- 4.7 (hours), r espectively. Although these values were comparable on average to those prev iously reported, there were noticeable differences with respect to the vari ous time courses of drug plasma concentration among each patient. Conclusio n: Computations speculated that the trough and peak plasma concentrations a s well as the AUC at steady-state change significantly depending on each pa tient. It suggests that individual pharmacokinetic values of lamivudine sho uld be determined before deciding the optimal administration dose for speci fic patients.