Analgesic and anti-inflammatory actions of robenacoxib in acute joint inflammation in dog.
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 ED(50) 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 ED(50) 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.
Schmid
V B
VB
Novartis Centre de Recherche Santé Animale SA, St-Aubin, Switzerland. vincent.schmid@novartis.com
Spreng
D E
DE
Seewald
W
W
Jung
M
M
Lees
P
P
King
J N
JN
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D004159:Diphenylamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004283:Dog Diseases / Q000139:chemically induced* / Q000188:drug therapy; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D008297:Male; D000077239:Meloxicam; D010648:Phenylacetates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013585:Synovitis / Q000139:chemically induced / Q000662:veterinary*; D013843:Thiazines / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use; D014527:Uric Acid / Q000633:toxicity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010648:Phenylacetates; D013843:Thiazines; D013844:Thiazoles; D014527:Uric Acid; D004159:Diphenylamine; D000077239:Meloxicam; C551524:robenacoxib