Giraudel, J M and Toutain, P L and King, J N and Lees, P (2009) Differential inhibition of cyclooxygenase isoenzymes in the cat by the NSAID robenacoxib. JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS, 32 (1). pp. 31-40.
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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.
| Item Type: | Article |
|---|---|
| RVC Publication Type: | Research (full) paper |
| WoS ID: | 000262478500003 |
| DOI: | https://doi.org/10.1111/j.1365-2885.2008.01031.x |
| Departments: | Comparative Biomedical Sciences |
| Research Programmes: | Comparative Physiology & Medicine > Cardiovascular and Inflammation Biology and Metabolism |
| Depositing User: | RVC Auto-import |
| Last Modified: | 21 Nov 2020 14:24 |
| URI: | https://researchonline.rvc.ac.uk/id/eprint/1788 |
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