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

• 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
• ISSN: 0140-7783; 1365-2885
• DOI: 10.1111/j.1365-2885.2008.01016.x

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.