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 greater than or equal to7 days of twice daily administration, and again over a 24-hour period after greater than or equal to7 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 (C-max) 2077 +/- 816 mug/L; trough plasma concentration (C-min) 332 +/- 219 mug/L; elimination half-life (t1/2 beta) 6.1 +/-1.9h; time to C-max (t(max)) 1.6 +/- 0.7h; average concentration over the dosage interval (C-av) 711 +/- 269 mug/L; and area under the concentration-time curve (AUC) over 2 dosage intervals (24h) 17 085 +/- 6464 mug (.) h/L. Corresponding values after administration of 300mg once daily were: C-max 3461 +/- 854 mug/L; C-min 146 +/- 87 mug/L; t(1)/(2)beta, 7.9 3.4h; t(max) 2.2 +/- 1.3h; C-av 705 +/- 177 mug/L; and AUC over 1 dosage interval (24h) 16 644 +/- 4150 mug h/L. Statistical analysis showed a significant difference (p < 0.05) between the 2 schedules for C-max, and C-min 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.