PHARMACOKINETICS OF ACYCLOVIR IN PATIENTS UNDERGOING CONTINUOUS VENOVENOUS HEMODIALYSIS

The pharmacokinetics of acyclovir in three patients undergoing continu ous venovenous hemodialysis was investigated. Acyclovir was administer ed as an intravenous infusion over 1 hour at a dose of 5 mg/kg daily i n one patient and 10 mg/kg every 48 hours in two patients. Samples fro m the arterial and venous blood lines and from ultrafiltrate were coll ected to calculate pharmacokinetic parameters, sieving coefficient and clearance of ultrafiltration. Plasma concentrations of acyclovir were assessed by high-performance Liquid chromatography. Peak plasma conce ntrations 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 approx imately half those found in patients with renal impairment. The cleara nce by ultrafiltration was from 17.4 to 22.3 ml/minute and reached nea rly 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 ra nging from 6.7 to 13.0 mg/hour. These data should be taken into accoun t to optimize drug therapy in patients on continuous hemodialysis. Unt il formal guidelines are defined, acyclovir dosage should be adjusted according to monitoring of plasma drug concentrations.