Steady-State Pharmacokinetics of Lamivudine in Human Immunodeficiency Virus-Infected Patients with End-Stage Renal Disease Receiving Chronic Dialysis

摘要

The steady-state pharmacokinetics of lamivudine were evaluated in 11 subjects with human immunodeficiency virus infection and end-stage renal disease, 9 of whom were receiving hemodialysis and 2 of whom were receiving chronic ambulatory peritoneal dialysis (CAPD). All subjects received 150 mg of lamivudine daily for at least 2 weeks prior to sampling for determination of the pharmacokinetics of lamivudine over a 24-h period on 2 consecutive days. On the first day, subjects received 150 mg of oral lamivudine and underwent dialysis (hemodialysis or CAPD). On the second day, subjects received another 150 mg of oral lamivudine but dialysis was not performed. For the subjects undergoing hemodialysis, the geometric mean predose serum lamivudine concentration was 1.14 μg/ml (95% confidence interval [CI], 0.83 to 1.58 μg/ml), the geometric mean maximum concentration in serum (Cmax) was 3.77 μg/ml (95% CI, 3.01 to 4.71 μg/ml), and the geometric mean area under the serum concentration-time curve from time zero to 24 h (AUC0-24) was 49.8 μg · h/ml (95% CI 39.1 to 63.6 μg · h/ml). Hemodialysis removed approximately 28 mg of lamivudine but had no significant effect on Cmax or AUC0-24. In the absence of hemodialysis, the geometric mean lamivudine terminal elimination half-life was 17.2 h (95% CI, 10.5 to 28.1 h), whereas the geometric mean intradialysis half-life of lamivudine was 5.3 h (95% CI, 3.4 to 8.2 h). The pharmacokinetics of lamivudine in subjects undergoing CAPD were similar to those in subjects undergoing hemodialysis. CAPD removed 24 mg of lamivudine over a 24-h period but had no effect on Cmax or AUC0-24. Pharmacokinetic modeling suggests that a lamivudine dose of 25 mg daily in hemodialysis subjects would provide serum exposure similar to that provided by a dose of 150 mg twice daily in patients with normal renal function.