Effect of renal failure on the pharmacokinetics of acyclovir

Abstract

To determine the effect of renal failure on the pharmacokinetics of acyclovir in patients with end-stage renal disease (ESRD), we studied six anuric subjects on chronic hemodialysis. Each subject received a single one-hour intravenous infusion of acyclovir (2.5 mg/kg). We compared these anuric subjects with 13 subjects with normal renal function (NRF) who had received a single dose of acyclovir (2.5 to 15 mg/kg) in an identical fashion. The kinetics were well-described by a two-compartment open model. The mean terminal plasma half-life of acyclovir in subjects with ESRD was 19.5 ± 5.9 hours (mean ± SD) compared with 2.9 ± 0.8 hours in our subjects with NRF. In subjects with renal failure the mean (± SD) peak, eight- and 24-hour plasma acyclovir concentrations were 37.5 ± 23.3, 10.3 ± 2.9, and 6.4 ± 2.4, μ M respectively. Forty-eight hours after the start of acyclovir infusion, the subjects were hemodialyzed for six hours. The pre- and post-hemodialysis acyclovir plasma levels were 2.74 ± 1.38 and 1.11 ± 0.60 μ M, respectively. The total body clearance of acyclovir (28.6 ± 9.5 ml/min/1.73 m 2) in ESRD was found to be approximately 10 percent of that previously seen in subjects with normal renal function (307 ± 98.4 mg/min/1.73 m 2). The volume of distribution at steady state was significantly less in the subjects with ESRD than in subjects with NRF. Acyclovir was readily hemodialyzable with an extraction coefficient of 0.45 ± 0.12 and a fourfold enhancement in the elimination of acyclovir during dialysis. Suggestions for acyclovir dosage modifications for patients with ESRD are provided.