PHARMACOKINETICS OF GANCICLOVIR IN HEART-TRANSPLANT PATIENTS UNDERGOING CONTINUOUS VENOVENOUS HEMODIALYSIS

The pharmacokinetics of ganciclovir in patients with severe renal dysfunction is poorly defined. In this paper, we report the pharmacokinetics of ganciclovir in three anuric heart transplant patients under continuous venovenous hemodialysis (CVVHD). Ganciclovir was administered at a dose of 5 mg/kg every 48 h for at least 9 days. Samples from the arterial and venous blood lines and from ultrafiltrate were collected to calculate pharmacokinetic parameters, clearance of ultrafiltration, and sieving coefficient. Ganciclovir concentrations were determined by high-performance liquid chromatography. Pharmacokinetic parameters (mean +/- SD) were the following: t1/2 beta 18.9 +/- 2.2 h, Cl 0.42 +/- 0.08 ml/min/kg, V(dss) 0.68 +/- 0.10 L/kg. At the steady state the clearance of ultrafiltration was 12.9 +/- 1.9 ml/min (or 130 L/week) and the sieving coefficient was 0.84 +/- 0.08 with an average fraction of 89.7 +/- 10.6% of the administered dose removed by CVVHD. These results show that CVVHD is highly effective in removing ganciclovir from plasma. Furthermore, CVVHD appears more effective than intermittent hemodialysis. These data should be taken into account to optimize dosage adjustment of ganciclovir in patients under CVVHD, and until guidelines are available, careful monitoring of drug concentrations is recommended.