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 ED50 of 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.