Analgesic and anti-inflammatory actions of robenacoxib in acute joint inflammation in dog

• Published in: Journal of veterinary pharmacology and therapeutics 2010-04, Vol.33 (2), p.118-131
• Main Authors: SCHMID, V.B, SPRENG, D.E, SEEWALD, W, JUNG, M, LEES, P, KING, J.N
• Format: Article
• Language: English
• Subjects: acute course; analgesic effect; analgesics; Animals; anti-inflammatory activity; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Area Under Curve; biochemical mechanisms; blood chemistry; Diphenylamine - administration & dosage; Diphenylamine - analogs & derivatives; Diphenylamine - pharmacokinetics; Diphenylamine - therapeutic use; dog diseases; Dog Diseases - chemically induced; Dog Diseases - drug therapy; Dogs; dosage; dose response; Dose-Response Relationship, Drug; drug therapy; Female; Half-Life; inflammation; inhibitors; Male; meloxicam; monosodium urate crystals; new drugs; nonsteroidal anti-inflammatory agents; pain; Phenylacetates - administration & dosage; Phenylacetates - pharmacokinetics; Phenylacetates - therapeutic use; prostaglandin synthase; robenacoxib; stifle; subcutaneous injection; swelling (physiological); synovitis; Synovitis - chemically induced; Synovitis - veterinary; Thiazines - therapeutic use; Thiazoles - therapeutic use; Uric Acid - toxicity
• ISSN: 0140-7783; 1365-2885
• DOI: 10.1111/j.1365-2885.2009.01117.x

The objectives of this study were to establish dose-response and blood concentration-response relationships for robenacoxib, a novel nonsteroidal anti-inflammatory drug with selectivity for inhibition of the cyclooxygenase (COX)-2 isoenzyme, in a canine model of synovitis. Acute synovitis of the stifle joint was induced by intra-articular injection of sodium urate crystals. Robenacoxib (0.25, 0.5, 1.0, 2.0 and 4.0 mg/kg), placebo and meloxicam (0.2 mg/kg) were administered subcutaneously (s.c.) 3 h after the urate crystals. Pharmacodynamic endpoints included data from forceplate analyses, clinical orthopaedic examinations and time course of inhibition of COX-1 and COX-2 in ex vivo whole blood assays. Blood was collected for pharmacokinetics. Robenacoxib produced dose-related improvement in weight-bearing, pain and swelling as assessed objectively by forceplate analysis (estimated ED₅₀ was 1.23 mg/kg for z peak force) and subjectively by clinical orthopaedic assessments. The analgesic and anti-inflammatory effects of robenacoxib were significantly superior to placebo (0.25-4 mg/kg robenacoxib) and were non-inferior to meloxicam (0.5-4 mg/kg robenacoxib). All dosages of robenacoxib produced significant dose-related inhibition of COX-2 (estimated ED₅₀ was 0.52 mg/kg) but no inhibition of COX-1. At a dosage of 1-2 mg/kg administered s.c., robenacoxib should be at least as effective as 0.2 mg/kg of meloxicam in suppressing acute joint pain and inflammation in dogs.