title: Evaluation of the dose-response relationship of oral robenacoxib in urate crystal-induced acute stifle synovitis in dogs.
abstract: The objective of the study was to establish the dose-response relationship for robenacoxib, a selective cyclooxygenase (COX)-2 inhibitor, in a urate crystal model of acute synovitis. In a randomized partial Latin square design trial, 12 beagle dogs were administered orally single doses of robenacoxib (0.5, 1, 2, 4 and 8 mg/kg), placebo and the positive control meloxicam (0.1 mg/kg), 3 h after injection of sodium urate crystals into a stifle joint. Dogs were assessed for weight bearing on a force plate and by subjective clinical orthopaedic observations. Robenacoxib produced dose-dependent improvement in weight bearing, and decreased pain on palpation and joint swelling, over the dose range 0.5-2 mg/kg with no further increase in effect over the range 2-8 mg/kg. For weight bearing on the force plate, the ED50of robenacoxib was 0.6-0.8 mg/kg. The onset of action and time to peak effect of robenacoxib were faster (respectively, 2-2.5 h and 3-5 h) than for meloxicam (respectively, 3 h and 6 h). Robenacoxib significantly inhibited COX-2 at all doses, with dose-related activity. Robenacoxib did not inhibit COX-1 over the dose range 0.5-4 mg/kg, but produced transient inhibition at 8 mg/kg. In conclusion, oral administration of robenacoxib over the dose range 0.5-8 mg/kg demonstrated significant analgesic and anti-inflammatory efficacy in dogs.
authors: Elanco Animal Health Research Centre, St-Aubin, Switzerland.
authors: L R
authors: LR
authors: Borer
authors: Elanco Animal Health Inc., Basel, Switzerland.
authors: W
authors: W
authors: Seewald
authors: Elanco Animal Health Research Centre, St-Aubin, Switzerland.
authors: J E
authors: JE
authors: Peel
authors: Elanco Animal Health Inc., Basel, Switzerland.
authors: J N
authors: JN
authors: King
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D004159:Diphenylamine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D004283:Dog Diseases / Q000139:chemically induced* / Q000188:drug therapy; D004285:Dogs; D007794:Lameness, Animal; D010648:Phenylacetates / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013264:Stifle / Q000187:drug effects*; D013585:Synovitis / Q000662:veterinary*; D014527:Uric Acid / Q000633:toxicity*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D010648:Phenylacetates; D014527:Uric Acid; D004159:Diphenylamine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C551524:robenacoxib