Pharmacokinetics of ganciclovir and valganciclovir in the adult horse

Equine herpes myeloencephalopathy, resulting from equine herpes virus type 1 (EHV-1) infection, is associated with substantial morbidity and mortality in the horse. As compared to other antiviral drugs, such as acyclovir, ganciclovir has enhanced potency against EHV-1. This study investigated the pharmacokinetics of ganciclovir and its oral prodrug, valganciclovir, in six adult horses in a randomized cross-over design. Ganciclovir sodium was administered intravenously as a slow bolus at a dose of 2.5mg/kg, and valganciclovir was administered orally at a dose of 1800mg per horse. Intravenously administered ganciclovir disposition was best described by a three-compartment model with a prolonged terminal half-life of 72 +/- 9h. Following the oral administration of valganciclovir, the mean observed maximum serum ganciclovir concentration was 0.58 +/- 0.37g/mL, and bioavailability of ganciclovir from oral valganciclovir was 41 +/- 20%. Superposition predicted that oral dosing of 1800-mg valganciclovir two times daily would fail to produce and maintain effective plasma concentrations of ganciclovir. However, superposition suggested that i.v. administration of ganciclovir at 2.5mg/kg every 8h for 24h followed by maintenance dosing of 2.5mg/kg every 12h would maintain effective ganciclovir serum concentrations in most horses throughout the dosing interval.