Pharmacokinetic/pharmacodynamic modelling of robenacoxib in a feline tissue cage model of inflammation
Article first published online: 18 JUL 2011
© 2011 Blackwell Publishing Ltd
Journal of Veterinary Pharmacology and Therapeutics
Volume 35, Issue 1, pages 19–32, February 2012
How to Cite
PELLIGAND, L., KING, J. N., TOUTAIN, P. L., ELLIOTT, J. and LEES, P. (2012), Pharmacokinetic/pharmacodynamic modelling of robenacoxib in a feline tissue cage model of inflammation. Journal of Veterinary Pharmacology and Therapeutics, 35: 19–32. doi: 10.1111/j.1365-2885.2011.01288.x
- Issue published online: 6 JAN 2012
- Article first published online: 18 JUL 2011
- (Paper received 1 October 2010; accepted for publication 2 February 2011)
Pelligand, L., King, J. N., Toutain, P. L., Elliott, J., Lees, P. Pharmacokinetic/pharmacodynamic modelling of robenacoxib in a feline tissue cage model of inflammation. J. vet. Pharmacol. Therap. 35, 19–32.
Robenacoxib is a novel nonsteroidal anti-inflammatory drug developed for use in cats. It is a highly selective COX-2 inhibitor. Results from previous feline studies showed that, despite a short half-life in blood, the effect of robenacoxib persisted for 24 h in clinical studies. A tissue cage model of acute inflammation was used to determine robenacoxib’s pharmacokinetics and its ex vivo and in vivo selectivity for COX-1 and COX-2 using serum TxB2 and exudate PGE2 as surrogate markers for enzyme activity, respectively. After intravenous, subcutaneous and oral administration (2 mg/kg), the clearance of robenacoxib from blood was rapid (0.54–0.71 L·h/kg). The mean residence time (MRT) in blood was short (0.4, 1.9 and 3.3 h after intravenous, subcutaneous and oral administration, respectively), but in exudate MRT was approximately 24 h regardless of the route of administration. Robenacoxib inhibition of COX-1 in blood was transient, occurring only at high concentrations, but inhibition of COX-2 in exudate persisted to 24 h. The potency ratio (IC50 COX-1: IC50 COX-2) was 171:1, and slopes of the concentration–effect relationship were 1.36 and 1.12 for COX-1 and COX-2, respectively. These data highlight the enzymatic selectivity and inflamed tissue selectivity of robenacoxib and support the current recommendation of once-daily administration.