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  • Author or Editor: David J. Maggs x
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Abstract

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 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 (Cmax) 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 (AUC0→∞) 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 AUC0→∞ from phase 1. Dose-normalized penciclovir Cmaxfollowing 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 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.

Full access
in American Journal of Veterinary Research

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 (Cmax) 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 Cmax and time to Cmax values. Therefore, the lower dose may have similar antiviral efficacy to that proven for the higher dose.

Full access
in American Journal of Veterinary Research