Pharmacokinetic modeling of penciclovir and brl42359 in the plasma and tears of healthy cats to optimize dosage recommendations for oral administration of famciclovir

Lionel Sebbag, Sara M Thomasy, Andrew P. Woodward, Heather K Knych, David J Maggs

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

OBJECTIVES To determine, following oral administration of famciclovir, pharmacokinetic (PK) parameters for 2 of its metabolites (penciclovir and BRL42359) in plasma and tears of healthy cats so that famciclovir dosage recommendations for the treatment of herpetic disease can be optimized. ANIMALS 7 male domestic shorthair cats. PROCEDURES In a crossover study, each of 3 doses of famciclovir (30, 40, or 90 mg/kg) was administered every 8 or 12 hours for 3 days. Six cats were randomly assigned to each dosage regimen. Plasma and tear samples were obtained at predetermined times after famciclovir administration. Pharmacokinetic parameters were determined for BRL42359 and penciclovir by compartmental and noncompartmental methods. Pharmacokinetic-pharmacodynamic (PK-PD) indices were determined for penciclovir and compared among all dosage regimens. RESULTS Compared with penciclovir concentrations, BRL42359 concentrations were 5- to 11-fold greater in plasma and 4- to 7-fold greater in tears. Pharmacokinetic parameters and PK-PD indices for the 90 mg/kg regimens were superior to those for the 30 and 40 mg/kg regimens, regardless of dosing frequency. Penciclovir concentrations in tears ranged from 18% to 25% of those in plasma. Administration of 30 or 40 mg/kg every 8 hours achieved penciclovir concentrations likely to be therapeutic in plasma but not in tears. Penciclovir concentrations likely to be therapeutic in tears were achieved only with the two 90 mg/kg regimens. CONCLUSIONS AND CLINICAL RELEVANCE In cats, famciclovir absorption is variable and its metabolism saturable. Conversion of BRL42359 to penciclovir is rate limiting.The recommended dosage of famciclovir is 90 mg/kg every 12 hours for cats infected with feline herpesvirus.

Original languageEnglish (US)
Pages (from-to)833-845
Number of pages13
JournalAmerican Journal of Veterinary Research
Volume77
Issue number8
DOIs
StatePublished - Aug 1 2016

Fingerprint

Tears
oral administration
pharmacokinetics
Oral Administration
Cats
Pharmacokinetics
cats
dosage
Felid herpesvirus 1
therapeutics
pharmacology
famciclovir
penciclovir
Herpesviridae
Felidae
Cross-Over Studies
metabolites
metabolism
Therapeutics
sampling

ASJC Scopus subject areas

  • veterinary(all)

Cite this

@article{94d38640d83e4a7696ed6e7ba4f8cbc1,
title = "Pharmacokinetic modeling of penciclovir and brl42359 in the plasma and tears of healthy cats to optimize dosage recommendations for oral administration of famciclovir",
abstract = "OBJECTIVES To determine, following oral administration of famciclovir, pharmacokinetic (PK) parameters for 2 of its metabolites (penciclovir and BRL42359) in plasma and tears of healthy cats so that famciclovir dosage recommendations for the treatment of herpetic disease can be optimized. ANIMALS 7 male domestic shorthair cats. PROCEDURES In a crossover study, each of 3 doses of famciclovir (30, 40, or 90 mg/kg) was administered every 8 or 12 hours for 3 days. Six cats were randomly assigned to each dosage regimen. Plasma and tear samples were obtained at predetermined times after famciclovir administration. Pharmacokinetic parameters were determined for BRL42359 and penciclovir by compartmental and noncompartmental methods. Pharmacokinetic-pharmacodynamic (PK-PD) indices were determined for penciclovir and compared among all dosage regimens. RESULTS Compared with penciclovir concentrations, BRL42359 concentrations were 5- to 11-fold greater in plasma and 4- to 7-fold greater in tears. Pharmacokinetic parameters and PK-PD indices for the 90 mg/kg regimens were superior to those for the 30 and 40 mg/kg regimens, regardless of dosing frequency. Penciclovir concentrations in tears ranged from 18{\%} to 25{\%} of those in plasma. Administration of 30 or 40 mg/kg every 8 hours achieved penciclovir concentrations likely to be therapeutic in plasma but not in tears. Penciclovir concentrations likely to be therapeutic in tears were achieved only with the two 90 mg/kg regimens. CONCLUSIONS AND CLINICAL RELEVANCE In cats, famciclovir absorption is variable and its metabolism saturable. Conversion of BRL42359 to penciclovir is rate limiting.The recommended dosage of famciclovir is 90 mg/kg every 12 hours for cats infected with feline herpesvirus.",
author = "Lionel Sebbag and Thomasy, {Sara M} and Woodward, {Andrew P.} and Knych, {Heather K} and Maggs, {David J}",
year = "2016",
month = "8",
day = "1",
doi = "10.2460/ajvr.77.8.833",
language = "English (US)",
volume = "77",
pages = "833--845",
journal = "American Journal of Veterinary Research",
issn = "0002-9645",
publisher = "American Veterinary Medical Association",
number = "8",

}

TY - JOUR

T1 - Pharmacokinetic modeling of penciclovir and brl42359 in the plasma and tears of healthy cats to optimize dosage recommendations for oral administration of famciclovir

AU - Sebbag, Lionel

AU - Thomasy, Sara M

AU - Woodward, Andrew P.

AU - Knych, Heather K

AU - Maggs, David J

PY - 2016/8/1

Y1 - 2016/8/1

N2 - OBJECTIVES To determine, following oral administration of famciclovir, pharmacokinetic (PK) parameters for 2 of its metabolites (penciclovir and BRL42359) in plasma and tears of healthy cats so that famciclovir dosage recommendations for the treatment of herpetic disease can be optimized. ANIMALS 7 male domestic shorthair cats. PROCEDURES In a crossover study, each of 3 doses of famciclovir (30, 40, or 90 mg/kg) was administered every 8 or 12 hours for 3 days. Six cats were randomly assigned to each dosage regimen. Plasma and tear samples were obtained at predetermined times after famciclovir administration. Pharmacokinetic parameters were determined for BRL42359 and penciclovir by compartmental and noncompartmental methods. Pharmacokinetic-pharmacodynamic (PK-PD) indices were determined for penciclovir and compared among all dosage regimens. RESULTS Compared with penciclovir concentrations, BRL42359 concentrations were 5- to 11-fold greater in plasma and 4- to 7-fold greater in tears. Pharmacokinetic parameters and PK-PD indices for the 90 mg/kg regimens were superior to those for the 30 and 40 mg/kg regimens, regardless of dosing frequency. Penciclovir concentrations in tears ranged from 18% to 25% of those in plasma. Administration of 30 or 40 mg/kg every 8 hours achieved penciclovir concentrations likely to be therapeutic in plasma but not in tears. Penciclovir concentrations likely to be therapeutic in tears were achieved only with the two 90 mg/kg regimens. CONCLUSIONS AND CLINICAL RELEVANCE In cats, famciclovir absorption is variable and its metabolism saturable. Conversion of BRL42359 to penciclovir is rate limiting.The recommended dosage of famciclovir is 90 mg/kg every 12 hours for cats infected with feline herpesvirus.

AB - OBJECTIVES To determine, following oral administration of famciclovir, pharmacokinetic (PK) parameters for 2 of its metabolites (penciclovir and BRL42359) in plasma and tears of healthy cats so that famciclovir dosage recommendations for the treatment of herpetic disease can be optimized. ANIMALS 7 male domestic shorthair cats. PROCEDURES In a crossover study, each of 3 doses of famciclovir (30, 40, or 90 mg/kg) was administered every 8 or 12 hours for 3 days. Six cats were randomly assigned to each dosage regimen. Plasma and tear samples were obtained at predetermined times after famciclovir administration. Pharmacokinetic parameters were determined for BRL42359 and penciclovir by compartmental and noncompartmental methods. Pharmacokinetic-pharmacodynamic (PK-PD) indices were determined for penciclovir and compared among all dosage regimens. RESULTS Compared with penciclovir concentrations, BRL42359 concentrations were 5- to 11-fold greater in plasma and 4- to 7-fold greater in tears. Pharmacokinetic parameters and PK-PD indices for the 90 mg/kg regimens were superior to those for the 30 and 40 mg/kg regimens, regardless of dosing frequency. Penciclovir concentrations in tears ranged from 18% to 25% of those in plasma. Administration of 30 or 40 mg/kg every 8 hours achieved penciclovir concentrations likely to be therapeutic in plasma but not in tears. Penciclovir concentrations likely to be therapeutic in tears were achieved only with the two 90 mg/kg regimens. CONCLUSIONS AND CLINICAL RELEVANCE In cats, famciclovir absorption is variable and its metabolism saturable. Conversion of BRL42359 to penciclovir is rate limiting.The recommended dosage of famciclovir is 90 mg/kg every 12 hours for cats infected with feline herpesvirus.

UR - http://www.scopus.com/inward/record.url?scp=84979686999&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979686999&partnerID=8YFLogxK

U2 - 10.2460/ajvr.77.8.833

DO - 10.2460/ajvr.77.8.833

M3 - Article

VL - 77

SP - 833

EP - 845

JO - American Journal of Veterinary Research

JF - American Journal of Veterinary Research

SN - 0002-9645

IS - 8

ER -