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.

Use of antiviral medications against equine herpes virus associated disorders

“…In one study, at the higher dosage of 20 mg/kg bwt, bioavailability was 2.8% with a mean ± s.d. C max of 0.19 ± 0.10 µg/ml (Bentz et al. 2006).…”

“…In Horse 1 of that series, blood was collected at various times during treatment to measure serum acyclovir concentrations. On Day 28 of acyclovir treatment, prior to the next dosing of acyclovir (serum trough concentration), the serum concentration of acyclovir was 0.26 µg/ml, based on measurement via high‐performance liquid chromatography (Bentz et al. 2006).…”

“…Based on 3 pharmacokinetic studies in adult horses, the administration of a single dose of acyclovir orally at 10 or 20 mg/kg bwt has poor bioavailability and low maximum measured serum drug concentrations (C max ) (Wilkins et al. 2005; Bentz et al. 2006; Garre et al.…”

“…Recent investigations have described the pharmacokinetic characteristics of these drugs, but proven clinical benefit is, as of yet, lacking (Wilkins et al. 2005; Bentz et al. 2006; Garre et al.…”

Disease Remission in a Horse with EHV‐5‐Associated Lymphoma

“…These drugs are incorporated into viral DNA and therefore terminate the growing viral DNA chain. Although the pharmacokinetics of acyclovir indicate that the bioavailability of the drug is low (2.8%), successful treatment of EMPF has been achieved using this medication, suggesting that accumulation occurs over time . Although valacyclovir, the prodrug of acyclovir, results in 10‐times‐higher Cmax and 8‐times‐higher bioavailability, the administration of this drug over a significant amount of time was cost prohibitive.…”