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.


METHODS
8 adult cats.


METHODS
A balanced crossover design was used. Phase I consisted of a single administration (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-->)) 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-->) from phase 1. Dose-normalized penciclovir C(max)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
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.
Thomasy
Sara M
SM
K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
Maggs
David J
DJ
Moulin
Nicole K
NK
Stanley
Scott D
SD
D015075:2-Aminopurine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000212:Acyclovir / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D002415:Cats / Q000097:blood / Q000378:metabolism*; D018592:Cross-Over Studies; D004347:Drug Interactions; D000077595:Famciclovir; D005260:Female; D006147:Guanine; D006207:Half-Life; D011355:Prodrugs / Q000494:pharmacology*; D013047:Specific Pathogen-Free Organisms
D000998:Antiviral Agents; D011355:Prodrugs; C053539:penciclovir; D015075:2-Aminopurine; D006147:Guanine; D000077595:Famciclovir; D000212:Acyclovir