Development and validation of a new model of inflammation in the cat and selection of surrogate endpoints for testing anti-inflammatory drugs

Authors


J. M. Giraudel, UMR 181 de Physiopathologie et Toxicologie Expérimentales INRA/ENVT, Ecole Nationale Vétérinaire de Toulouse, 23 chemin des Capelles, B.P. 87614, 31076 Toulouse Cedex 3, France. E-mail: j.giraudel@envt.fr

Abstract

In laboratory animals many models of inflammation have been developed for preclinical evaluation of the pharmacological profiles of nonsteroidal anti-inflammatory drugs (NSAIDs). In contrast, in species of veterinary interest, including the cat, NSAIDs have been studied mainly using dose-titration or dose-confirmation studies in clinical subjects. This is due to the scarcity of appropriate animal models and to the associated lack of quantitative validated endpoints describing the magnitude and time course of drug response. Determination of pharmacokinetic/pharmacodynamic (PK/PD) relationships provides a powerful approach for the selection of effective and safe dosage regimens. In this study, a paw inflammation model in the cat was developed for the preclinical evaluation of NSAIDs using PK/PD modelling. Subcutaneous injection of 500 mg kaolin in the paw produced a well-defined and reproducible inflammatory response that lasted 4–5 days. Several endpoints were assessed for their clinical relevance and for their metrological performance (accuracy and reproducibility). Body temperature, lameness scoring, locomotion tests and possibly skin temperature were the most appropriate endpoints for testing the antipyretic, analgesic and anti-inflammatory effects of NSAIDs in the cat.

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