Pharmacokinetic/pharmacodynamic modelling of robenacoxib in a feline tissue cage model of inflammation

Abstract

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 TxB(2) and exudate PGE(2) 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 (IC(50) COX-1: IC(50) 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.

Evaluation of Oral Robenacoxib for the Treatment of Postoperative Pain and Inflammation in Cats: Results of a Randomized Clinical Trial

“…Once daily dosing with robenacoxib provided good efficacy over the dosing interval. These results support previous findings that robenacoxib has a relatively long duration of action despite its short blood half life, explained by concentration and persistence at sites of inflammation [13]. …”

Modeling of Large Pharmacokinetic Data Using Nonlinear Mixed‐Effects: A Paradigm Shift in Veterinary Pharmacology. A Case Study With Robenacoxib in Cats

“…Blood concentration time profiles were available from 83 cats. The demographics of the cats, dose/route of administration, and design of these studies (rich or sparse sampling strategy) are summarized in Table . Fourteen of these 83 cats received robenacoxib by both routes.…”

A Brief Overview of the Coxib Drugs in the Veterinary Field

“…Previous studies have revealed its pharmacokinetic properties via different administration routes including, intravenous, subcutaneous and oral administration in the dog and cat (Jung et al, 2009;Pelligand et al, 2012). In dogs, robenacoxib showed good bioavailability after oral (84%) and subcutaneous (88%) administration with a short blood half-life of 1 h (Jung et al, 2009).…”