Comparison of the plasma pharmacokinetics of lamivudine during twice and once daily administration in patients with HIV

Objective: To compare the plasma pharmacokinetics of lamivudine 150mg twice daily and 300mg once daily in patients with HIV-1 infection. Design: Nonblind, sequential, pharmacokinetic study. Participants: 13 patients with HIV-1 infection (median age 36 years). Methods: Patients were tested during twice daily and then once daily regimens of lamivudine. In both regimens, the total daily dose of lamivudine was identical (300 mg/day). Blood samples for pharmacokinetic analysis were taken over a 12-hour period after ≥7 days of twice daily administration, and again over a 24-hour period after 7 days of once daily administration. Results: 12 patients completed the study. Lamivudine pharmacokinetic parameters (mean±SD) after administration of 150mg twice daily were: peak plasma concentration (Cmax) 2077±816 μg/L; trough plasma concentration (Cmin) 332±219 μg/L; elimination half-life (t1/2β) 6.1±1.9h; time to Cmax(tmax) 1.6±0.7h; average concentration over the dosage interval (Cav) 711±269 μg/L; and area under the concentration-time curve (AUC) over 2 dosage intervals (24h) 17 085±6464 μg · h/L. Corresponding values after administration of 300mg once daily were: Cmax 3461±854 μg/L; Cmin 146±87 μg/L; t1/2β 7.9±3.4h; tmax 2.2±1.3h; Cav 705±177 μg/L; and AUC over 1 dosage interval (24h) 16 644±4150 μg · h/L. Statistical analysis showed a significant difference (p<0.05) between the 2 schedules for Cmax and Cmin values, whereas no significant differences emerged for the other parameters. Conclusions: Once daily lamivudine leads to a similar exposure in plasma as twice daily administration of the same total daily dose. Since once daily administration may result in improved compliance, these results provide the pharmacokinetic basis for using lamivudine in a once daily regimen. Randomised clinical studies are needed to confirm this pharmacokinetic finding.