Pharmacokinetics of ganciclovir in pediatric renal transplant recipients.

Abstract

Ganciclovir (GCV) is effective in preventing and treating cytomegalovirus (CMV) infection in solid organ transplant recipients. The aims of the present study were to determine the pharmacokinetics of GCV administered intravenously (IV) and orally (p.o.) as pre-emptive anti-CMV therapy in pediatric renal transplant recipients and to monitor trough levels and side-effects during pre-emptive therapy. Eleven pediatric renal transplant recipients (aged 11.0+/-3.9 years) were included. The diagnosis of CMV infection, based on two positive pp-65 CMV blood antigen tests at 1 week apart, was made at 39+/-12 days post renal transplantation. They received IV GCV at a dose of 5.0+/-0.3 mg/kg per 12 h for 15 days, followed by GCV p.o. at a dose of 46.7+/-8.2 mg/kg per 12 h for 3 months. Pharmacokinetics (PK) were studied at steady state and GCV plasma concentrations were measured by high-performance liquid chromatography. After IV GCV administration, PK parameters were: C(0)=0.84+/-0.66 microg/ml; C(max)=11.77+/-2.82 microg/ml; AUC(0-12 h)=42.29+/-17.57 microg/ml per hour; Cl=0.13+/-0.05 l/h per kg. After p.o. GCV administration, PK parameters were: C(0)=1.08+/-0.68 microg/ml; C(max)=2.70+/-1.07 microg/ml; AUC(0-12 h)=18.97+/-9.36 microg/ml per hour; Cl/F=2.97+/-1.42 l/h per kg. Bioavailability (F) was 4.9+/-1.2%. Pre-dose concentrations (C(0)) measured under p.o. GCV (n=51) were 1.29+/-0.80 microg/ml (8 C(0) values were below 0.5 microg/ml). Pp-65 CMV blood antigen tests became negative after 16+/-11 days of treatment. GCV was well tolerated. Because of the limited bioavailability, the recommended high doses of p.o. GCV (50 mg/kg per 12 h) were administered and were associated with trough levels over 0.5 microg/ml. In 1 patient who received an erroneously low dosage p.o., CMV resistance to GCV appeared, requiring foscarnet.