Pharmacokinetics of penciclovir in healthy cats following oral administration of famciclovir or intravenous infusion of penciclovir

Am J Vet Res. 2012 Jul;73(7):1092-9. doi: 10.2460/ajvr.73.7.1092.

Abstract

Objective: To investigate the pharmacokinetics of penciclovir in healthy cats following oral administration of famciclovir or IV infusion of penciclovir.

Animals: 6 cats.

Procedures: Cats received famciclovir (40 [n = 3] or 90 [3] mg/kg, PO, once) in a balanced crossover-design study; the alternate dose was administered after a ≥ 2-week washout period. After another washout period (≥ 4 weeks), cats received an IV infusion of penciclovir (10 mg/kg delivered over 1 hour). Plasma penciclovir concentrations were analyzed via liquid chromatography-mass spectrometry at fixed time points after drug administration.

Results: Mean ± SD maximum plasma concentration (C(max)) of penciclovir following oral administration of 40 and 90 mg of famciclovir/kg was 1.34 ± 0.33 μg/mL and 1.28 ± 0.42 μg/mL and occurred at 2.8 ± 1.8 hours and 3.0 ± 1.1 hours, respectively; penciclovir elimination half-life was 4.2 ± 0.6 hours and 4.8 ± 1.4 hours, respectively; and penciclovir bioavailability was 12.5 ± 3.0% and 7.0 ± 1.8%, respectively. Following IV infusion of penciclovir (10 mg/kg), mean ± SD penciclovir clearance, volume of distribution, and elimination half-life were 4.3 ± 0.8 mL/min/kg, 0.6 ± 0.1 L/kg, and 1.9 ± 0.4 hours, respectively.

Conclusions and clinical relevance: Penciclovir pharmacokinetics following oral administration of famciclovir were nonlinear within the dosage range studied, likely because of saturation of famciclovir metabolism. Oral administration of famciclovir at 40 or 90 mg/kg produced similar C(max) and time to C(max) values. Therefore, the lower dose may have similar antiviral efficacy to that proven for the higher dose.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Aminopurine / administration & dosage
  • 2-Aminopurine / analogs & derivatives*
  • 2-Aminopurine / blood
  • 2-Aminopurine / pharmacokinetics
  • Acyclovir / administration & dosage
  • Acyclovir / analogs & derivatives*
  • Acyclovir / blood
  • Acyclovir / pharmacokinetics
  • Administration, Oral
  • Animals
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / blood
  • Antiviral Agents / pharmacokinetics*
  • Area Under Curve
  • Biological Availability
  • Cats / metabolism*
  • Cross-Over Studies
  • Famciclovir
  • Female
  • Guanine
  • Half-Life
  • Male
  • Prodrugs / administration & dosage
  • Prodrugs / pharmacokinetics*

Substances

  • Antiviral Agents
  • Prodrugs
  • penciclovir
  • 2-Aminopurine
  • Guanine
  • Famciclovir
  • Acyclovir