title: Pharmacokinetics of acyclovir after single intravenous and oral administration to adult horses.
abstract: The purpose of the study reported here was to describe the bioavailability and pharmacokinetics of acyclovir after intravenous and oral administration to horses. Six healthy adult horses were used in a randomized cross-over study with a 3 x 3 Latin square design. Three treatments were administered to each horse: 10 mg of injectable acyclovir/kg of body weight in 1 L of normal saline delivered as an infusion over 15 minutes; 10 mg of acyclovir/kg in tablets by nasogastric intubation; and 20 mg of acyclovir/kg in tablets by nasogastric intubation. A 2-week washout period was provided between each treatment. Serum samples were obtained for acyclovir assay using reversed-phase, high-performance liquid chromatography with fluorescence detection. Deproteinated serum was injected onto a C18 column, and elution occurred under isocratic conditions. The limit of quantification was 0.04 microg/mL. The assay exhibited suitable accuracy, precision, and recovery. The IV data were analyzed by a 3-compartment model, and oral data were analyzed noncompartmentally. Intragastric acyclovir administration at either dose was associated with high variability in serum acyclovir-time profiles, low Cmax, and poor bioavailability. The dosage of 20 mg/kg was associated with mean (+/- SD) Cmax of 0.19 +/- 0.10 microg/mL, and bioavailability was 2.8%. Inhibition of equine herpesvirus has been reported to require significantly higher acyclovir concentrations than those obtained here. The results of this study do not support a therapeutic benefit for the oral administration of acyclovir up to doses of 20 mg/kg.
authors.affiliation: Department of Veterinary Clinical Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater 74078, USA. bradford.g.bentz@okstate.edu
authors.forename: Bradford G
authors.initials: BG
authors.lastname: Bentz
authors.forename: Lara K
authors.initials: LK
authors.lastname: Maxwell
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Erkert
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Royer
authors.forename: Michael S
authors.initials: MS
authors.lastname: Davis
authors.forename: Charles G
authors.initials: CG
authors.lastname: MacAllister
authors.forename: Cyril R
authors.initials: CR
authors.lastname: Clarke
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D005260:Female; D006566:Herpesviridae Infections / Q000188:drug therapy / Q000662:veterinary; D004861:Herpesvirus 1, Equid; D006734:Horse Diseases / Q000188:drug therapy; D006736:Horses / Q000378:metabolism*; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male
chemical_list: D000998:Antiviral Agents; D000212:Acyclovir