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). However, pharmacokinetic values of lamivudine will differ among individual patients. In addition, few studies regarding the pharmacokinetics of lamivudine in the Japanese people have so far been reported. Therefore, we have aimed to examine the variation in the pharmacokinetic values of lamiduvine present in six Japanese patients with HIV-1 infection.


METHODS
Lamivudine concentrations were measured in three hemophiliacs (HIV-1-asymptomatic carrier, AC) and three non-hemophiliacs (2 of these patients were AC and one had AIDS-related complex, ARC). In order to simulate the lamivudine plasma concentrations found in chronic oral administration, we added an absorption compartment to the two-compartment model.


RESULTS
The mean +/- SD of Tmax, Cmax, AUC(0 - infinity) and t1/2beta were 1.2 +/- 0.5 (hours), 1,280 +/- 267 (ng/ml), 6,778 +/- 2,763 (ng x h/ml), and 10.3 +/- 4.7 (hours), respectively. Although these values were comparable on average to those previously reported, there were noticeable differences with respect to the various time courses of drug plasma concentration among each patient.


CONCLUSIONS
Computations speculated that the trough and peak plasma concentrations as well as the AUC at steady-state change significantly depending on each patient. It suggests that individual pharmacokinetic values of lamivudine should be determined before deciding the optimal administration dose for specific patients.
Tatsunami
S
S
Radioisotope Research Institute, St. Marianna University School of Medicine, Kawasaki, Japan.
Ito
A
A
Kawata
K
K
Kuwabara
R
R
Fukutake
K
K
Yamada
K
K
D000328:Adult; D000465:Algorithms; D019380:Anti-HIV Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D005260:Female; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1; D006207:Half-Life; D006801:Humans; D019259:Lamivudine / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological
D019380:Anti-HIV Agents; D019259:Lamivudine