Differential inhibition of cyclooxygenase isoenzymes in the cat by the NSAID robenacoxib

Giraudel, J M; Toutain, P L; King, J N; Lees, P

Abstract

Robenacoxib is a new nonsteroidal anti-inflammatory drug (NSAID) developed for use in companion animal medicine. The objectives of this study were: to quantify the inhibitory actions of robenacoxib on cyclooxygenase (COX) isoenzymes in feline whole blood assays; to establish blood concentration-time profiles of robenacoxib after intravenous and subcutaneous dosing in the cat and; to predict the time courses of inhibition of COX isoforms by robenacoxib. COX-1 and COX-2 activities in heparinized feline whole blood samples were induced with calcium ionophore and lipopolysaccharide, respectively. Inhibition of thromboxane B-2 provided a marker of both COX-1 and COX-2 activities and a nonlinear parametric mixed effects modelling approach was used to establish the pharmacodynamic parameters describing this inhibition. Mean values (and prediction intervals) of IC50 were 28.9 (16.4-51.1) mu m (COX-1) and 0.058 (0.010-0.340) mu m (COX-2). These parameters were used to compute several selectivity indices. Selectivity IC ratios (COX-1:COX-2) were 502.3 (IC50/IC50), 451.6 (IC95/IC95) and 17.05 (IC20/IC80). Based on a clinically recommended dosage regimen of 2 mg/kg, it was predicted that the corresponding mean robenacoxib blood concentration over the first 12 h after drug administration corresponded to 5% inhibition of COX-1 and 90% inhibition of COX-2.

Citation

Giraudel, J. M., Toutain, P. L., King, J. N., & Lees, P. Differential inhibition of cyclooxygenase isoenzymes in the cat by the NSAID robenacoxib. Journal of Veterinary Pharmacology and Therapeutics, 32(1), 31-40. https://doi.org/10.1111/j.1365-2885.2008.01031.x

• Journal Article Type: Article
• Deposit Date: Nov 11, 2014
• Journal: JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
• Print ISSN: 0140-7783
• Publisher: American Academy of Veterinary Pharmacology and Therapeutics
• Volume: 32
• Issue: 1
• Pages: 31-40
• DOI: https://doi.org/10.1111/j.1365-2885.2008.01031.x
• Public URL: https://rvc-repository.worktribe.com/output/1425770
• Additional Information: Corporate Creators : Novartis Animal Health, Toulouse