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

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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 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 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.

Original languageEnglish (US)
Pages (from-to)1252-1258
Number of pages7
JournalAmerican Journal of Veterinary Research
Volume68
Issue number11
DOIs
StatePublished - Nov 2007

Fingerprint

oral administration
pharmacokinetics
Oral Administration
Cats
Pharmacokinetics
cats
Safety
dosage
Felid herpesvirus 1
Herpesviridae
Felidae
famciclovir
penciclovir
administered dose
Liquid Chromatography
Cross-Over Studies
liquid chromatography
half life
Area Under Curve
Half-Life

ASJC Scopus subject areas

  • veterinary(all)

Cite this

@article{8bfdd33fcf56403999541c5f7249e769,
title = "Pharmacokinetics and safety of penciclovir following oral administration of famciclovir to cats",
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 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 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.",
author = "Thomasy, {Sara M} and Maggs, {David J} and Moulin, {Nicole K.} and Stanley, {Scott D}",
year = "2007",
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doi = "10.2460/ajvr.68.11.1252",
language = "English (US)",
volume = "68",
pages = "1252--1258",
journal = "American Journal of Veterinary Research",
issn = "0002-9645",
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number = "11",

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TY - JOUR

T1 - Pharmacokinetics and safety of penciclovir following oral administration of famciclovir to cats

AU - Thomasy, Sara M

AU - Maggs, David J

AU - Moulin, Nicole K.

AU - Stanley, Scott D

PY - 2007/11

Y1 - 2007/11

N2 - 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 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 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.

AB - 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 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 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.

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