Pharmacokinetics of acyclovir in patients undergoing continuous venovenous hemodialysis

The pharmacokinetics of acyclovir in three patients undergoing continuous venovenous hemodialysis was investigated. Acyclovir was administered as an intravenous infusion over 1 hour at a dose of 5 mg/kg daily in one patient and 10 mg/kg every 48 hours in two patients. Samples from the arterial and venous blood lines and from ultrafiltrate were collected to calculate pharmacokinetic parameters, sieving coefficient and clearance of ultrafiltration. Plasma concentrations of acyclovir were assessed by high-performance liquid chromatography. Peak plasma concentrations were 9.3 mg/l for the patient receiving 5 mg/kg daily, 29.6 mg/l and 20.7 mg/l for the two patients with 10 mg/kg every 48 hours. The elimination half-life ranged from 8.8 to 11.2 hours and was approximately half those found in patients with renal impairment. The clearance by ultrafiltration was from 17.4 to 22.3 ml/minute and reached nearly 35% of the total clearance. The sieving coefficient ranged from 0.92 to 0.98 with an average rate of removal over the dosing interval ranging from 6.7 to 13.0 mg/hour. These data should be taken into account to optimize drug therapy in patients on continuous hemodialysis. Until formal guidelines are defined, acyclovir dosage should be adjusted according to monitoring of plasma drug concentrations.