title: Use of a pharmacokinetic/pharmacodynamic approach in the cat to determine a dosage regimen for the COX-2 selective drug robenacoxib.
abstract: 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.
authors.affiliation: Ecole Nationale Vétérinaire de Toulouse, UMR 181 Physiopathologie et Toxicologie Expérimentales INRA, ENVT, Toulouse Cedex, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Giraudel
authors.forename: J N
authors.initials: JN
authors.lastname: King
authors.forename: E C
authors.initials: EC
authors.lastname: Jeunesse
authors.forename: P
authors.initials: P
authors.lastname: Lees
authors.forename: P-L
authors.initials: PL
authors.lastname: Toutain
mesh_terms: D000042:Absorption; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002371:Cat Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D002415:Cats; D052246:Cyclooxygenase 2 Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D006207:Half-Life; D007249:Inflammation / Q000188:drug therapy / Q000662:veterinary*; D007279:Injections, Subcutaneous / Q000662:veterinary; D007794:Lameness, Animal / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008657:Metabolic Clearance Rate; D010147:Pain Measurement / Q000662:veterinary
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors