Clinical Pharmacology of Ganciclovir and Valganciclovir in Infants and Children - Abstract
Ganciclovir is an acyclic guanine nucleotide analogue and valganciclovir is the L-valyl ester prodrug of ganciclovir. Ganciclovir inhibits all herpes viruses and is especially active against cytomegalovirus. Ganciclovir inhibits viral DNA. Ganciclovir diphosphate and ganciclovir triphosphate are formed by host enzymes. The oral bioavailability of ganciclovir is < 10% whereas that of valganciclovir is about 60% and food further increases its bioavailability. Ganciclovir is effective in the treatment of cytomegalovirus retinitis. The intravenous dose of ganciclovir is 6 mg/ kg twice-daily in infants and in children it is 5 mg/kg twice-daily. Ganciclovir has been found efficacy and safe in infants and children but it may induce adverse-effects. The mean elimination half-life of ganciclovir is 2.4 hours and the mean distribution volume is about 700 ml/kg in infants. Ganciclovir is converted into ganciclovir triphosphate in human cytomegalovirus infected cells and the elimination of ganciclovir triphosphate is about 48 hours in these cells. Ganciclovir interacts with drugs and the treatment and prophylaxis with ganciclovir have been extensively studied in infants and children. Ganciclovir penetrates into the cerebrospinal fluid of infants and children in significant amounts and treated the meningitis caused by human herpesvirus 6 and by cytomegalovirus. Ganciclovir is poorly transferred across the human placenta. The aim of this study is to review the published data on ganciclovir dosing, efficacy and safety, effects, adverseeffects, pharmacokinetics, metabolism, drug interactions, therapeutic use, treatment, prophylaxis, penetration into the cerebrospinal fluid, and treatment of meningitis in infants and children, and the transfer across the human placenta.