1252 AJVR, Vol 68, No. 11, November 2007 F eline herpesvirus-1 is a major cause of respiratory and ocular disease in cats, with an estimated serop- revalence in feline populations of 50% to 97%. 1-3 Infec- tion of susceptible kittens with FHV-1 typically causes moderate to severe upper respiratory tract and ocular disease with approximately 100% morbidity. 4 Illness may be fatal, especially in young kittens. Following primary exposure, FHV-1 establishes lifelong neural latency in at least 80% of cats, and periods of viral re- activation occur throughout life in many of these cats. 5 Herpetic infection may be associated with conjunctivi- tis, 6 rhinosinusitis, 7 keratitis, 8 corneal sequestration, 9 eosinophilic keratitis, 9 anterior uveitis, 10 or dermati- tis. 11,12 As such, primary and recrudescent herpetic dis- ease in cats represents a diverse array of common and often frustrating clinical syndromes worldwide. Pharmacokinetics and safety of penciclovir following oral administration of famciclovir to cats Sara M. Thomasy, DVM, PhD; David J. Maggs, BVSc; Nicole K. Moulin, BS; Scott D. Stanley, PhD Objective—To investigate penciclovir pharmacokinetics following single and multiple oral administrations of famciclovir to cats. Animals—8 adult cats. Procedures—A balanced crossover design was used. Phase I consisted of a single admin- istration (62.5 mg, PO) of famciclovir. Phase II consisted of multiple doses of famciclovir (62.5 mg, PO) given every 8 or 12 hours for 3 days. Plasma penciclovir concentrations were assayed via liquid chromatography–mass spectrometry at fixed time points after famciclovir administration. Results—Following a single dose of famciclovir, the dose-normalized (15 mg/kg) maximum concentration (C max ) of penciclovir (350 ± 180 ng/mL) occurred at 4.6 ± 1.8 hours and mean ± SD apparent elimination half-life was 3.1 ± 0.9 hours. However, the dose-normalized area under the plasma penciclovir concentration-time curve extrapolated to infinity (AUC 0→∞ ) dur- ing phase I decreased with increasing dose, suggesting either nonlinear pharmacokinetics or interindividual variability among cats. Accumulation occurred following multiple doses of famciclovir administered every 8 hours as indicated by a significantly increased dose- normalized AUC, compared with AUC 0→∞ from phase 1. Dose-normalized penciclovir Cmax following administration of famciclovir every 12 or 8 hours (290 ± 150 ng/mL or 780 ± 250 ng/mL, respectively) was notably less than the in vitro concentration (3,500 ng/mL) required for activity against feline herpesvirus-1. Conclusions and Clinical Relevance—Penciclovir pharmacokinetics following oral fam- ciclovir administration in cats appeared complex within the dosage range studied. Fam- ciclovir dosages of 15 mg/kg administered every 8 hours to cats are unlikely to result in plasma penciclovir concentrations with activity against feline herpesvirus-1. (Am J Vet Res 2007;68:1252–1258) Presently, in the United States, there are no antivi- ral drugs approved for treatment of cats infected with FHV-1. However, several antiviral agents developed for Received December 21, 2006. Accepted April 23, 2007. From the K.L. Maddy Equine Analytical Chemistry Laboratory (Thomasy, Stanley) and Department of Surgical and Radiological Sciences (Maggs, Moulin), School of Veterinary Medicine, University of California, Davis, CA 95616. Presented in part at the annual forum of the American College of Veterinary Internal Medicine, Louisville, May–June 2006. Supported by the Center for Companion Animal Health, School of Veterinary Medicine, University of California, Davis, Calif. The authors thank Debbie Bee for technical assistance. Address correspondance to Dr. Maggs. ABBREVIATIONS FHV-1 Feline herpesvirus-1 C max Maximum detected plasma penciclovir concentration T max Time after oral administration at which C max was detected k el Elimination rate constant AUC Area under the plasma penciclovir con- centration-time curve t 1/2(λ z ) Apparent elimination half-life Cp(avg) Mean plasma penciclovir concentration during the dosing interval at steady state C ss(min) Minimum detected plasma penci- clovir concentration during the dosing interval at steady state Fluctuation ss Steady-state fluctuation AUC 0→τ฀ Area under the plasma penciclovir concentration-time curve during the dosing interval τ Administration interval AUC 00→∞ Area under the plasma penciclovir concentration-time curve extrapolat- ed to infinity Unauthenticated | Downloaded 08/15/22 10:33 AM UTC