Pharmacokinetics and safety of penciclovir following oral administration of famciclovir to cats

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 administration (62.5 mg, PO) of famciclovir. Phase 11 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 ->infinity)) during 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 ->infinity) from phase 1. Dose-normalized penciclovir C-max following administration of famcicloviro 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 famciclovir administration in cats appeared complex within the dosage range studied. Famciclovir 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.