title: Pharmacokinetics of ganciclovir and valganciclovir in the adult horse.
abstract: 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 2.5 mg/kg, and valganciclovir was administered orally at a dose of 1800 mg per horse. Intravenously administered ganciclovir disposition was best described by a three-compartment model with a prolonged terminal half-life of 72 ± 9 h. Following the oral administration of valganciclovir, the mean observed maximum serum ganciclovir concentration was 0.58 ± 0.37 μg/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 2.5 mg/kg every 8 h for 24 h followed by maintenance dosing of 2.5 mg/kg every 12 h would maintain effective ganciclovir serum concentrations in most horses throughout the dosing interval.
authors.affiliation: Department of Veterinary Clinical Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Carmichael
authors.forename: C
authors.initials: C
authors.lastname: Whitfield
authors.forename: L K
authors.initials: LK
authors.lastname: Maxwell
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D006736:Horses; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D000077562:Valganciclovir
chemical_list: D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir