Use of a pharmacokinetic/pharmacodynamic approach in the cat to determine a dosage regimen for the COX-2 selective drug robenacoxib

This study investigated the analgesic, anti-inflammatory and antipyretic efficacy of the new COX-2 selective inhibitor robenacoxib in the cat and established pharmacodynamic (PD) parameters for these effects. Robenacoxib, at a dosage of 2 mg/kg administered subcutaneously, was evaluated in a kaolin-...

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Bibliographic Details
Published in:	Journal of veterinary pharmacology and therapeutics Vol. 32; no. 1; pp. 18 - 30
Main Authors:	GIRAUDEL, J.M, KING, J.N, JEUNESSE, E.C, LEES, P, TOUTAIN, P.-L
Format:	Journal Article
Language:	English
Published:	Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01-02-2009 Blackwell Publishing Ltd Wiley-Blackwell
Subjects:	Absorption analgesic effect Animals anti-inflammatory activity Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics Anti-Inflammatory Agents, Non-Steroidal - therapeutic use antipyretics Area Under Curve Cat Diseases - chemically induced Cat Diseases - drug therapy Cat Diseases - pathology Cats Cyclooxygenase 2 Inhibitors - pharmacokinetics Cyclooxygenase 2 Inhibitors - therapeutic use Disease Models, Animal dosage drugs endpoints enzyme inhibitors Female Half-Life inflammation Inflammation - drug therapy Inflammation - veterinary Injections, Subcutaneous - veterinary Lameness, Animal - chemically induced Lameness, Animal - drug therapy Lameness, Animal - pathology Life Sciences Male Metabolic Clearance Rate nonsteroidal anti-inflammatory agents Pain Measurement - veterinary pharmacokinetics prostaglandin synthase robenacoxib temporal variation
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Summary:	This study investigated the analgesic, anti-inflammatory and antipyretic efficacy of the new COX-2 selective inhibitor robenacoxib in the cat and established pharmacodynamic (PD) parameters for these effects. Robenacoxib, at a dosage of 2 mg/kg administered subcutaneously, was evaluated in a kaolin-induced paw inflammation model in 10 cats, using both clinically relevant endpoints (lameness scoring, locomotion tests) and other indicators of inflammation (body and skin temperature, thermal pain threshold) to establish its pharmacological profile. A pharmacokinetic/pharmacodynamic (PK/PD) modelling approach, based on indirect response models, was used to describe the time course and magnitude of the responses to robenacoxib. All endpoints demonstrated good responsiveness to robenacoxib administration and both the magnitude and time courses of responses were well described by the indirect pharmacodynamic response models. Pharmacokinetic and clinically relevant pharmacodynamic parameters were used to simulate dosage regimens that will assist the planning of clinical trials and the selection of an optimal dosage regimen for robenacoxib in the cat.
Bibliography:	http://dx.doi.org/10.1111/j.1365-2885.2008.01016.x ark:/67375/WNG-K0XL8S25-F istex:7BC22FDD9241BEC7A22FEE9FA0F5422F9E67CB44 ArticleID:JVP1016 Current address of J. M. Giraudel: Novartis Centre de Recherche Santé Animale SA, CH‐1566 St‐Aubin FR, Switzerland
ISSN:	0140-7783 1365-2885
DOI:	10.1111/j.1365-2885.2008.01016.x