PHARMACOLOGICAL PROPERTIES
Pharmacotherapeutic group
Anti-inflammatory and anti-rheumatic products, nonsteroids, coxibs. ATC Vet Code: QM01AH91.
Pharmacodynamic properties
Robenacoxib is a non-steroidal anti-inflammatory drug (NSAID) of the coxib class. It is a potent and selective inhibitor of the cyclooxygenase 2 enzyme (COX-2).
The Cyclooxygenase enzyme (COX) is present in two forms. COX-1 is the constitutive form of the enzyme and has protective functions, e.g. in the gastrointestinal tract and kidneys. COX-2 is the inducible form of the enzyme and is responsible for the production of mediators including PGE2 which induce pain, inflammation or fever.
In an in vitro whole blood assay in dogs, robenacoxib was approximately 140 fold selective for COX-2 (IC50 0.04 μM) as compared to COX-1 (IC50 7.9 μM). Robenacoxib produced marked inhibition of COX-2 activity and had no effect on COX-1 activity in dogs at oral doses ranging from 0.5 to 4 mg/kg. Robenacoxib tablets are therefore COX-1 sparing at recommended doses in dogs. Robenacoxib had analgesic and anti-inflammatory actions in an inflammation model in dogs with single oral doses ranging from 0.5 to 8 mg/kg, with an ID50 of 0.8 mg/kg and a rapid onset of action (0.5 h). In clinical trials in dogs, robenacoxib reduced the lameness and inflammation associated with chronic osteoarthritis, and pain, inflammation and the need for rescue treatment in dogs undergoing soft tissue surgery.
Pharmacokinetic particulars
After oral administration of robenacoxib flavoured tablets at 1-2 mg/kg without food, peak blood concentrations are attained rapidly with a Tmax of 0.75 h, a Cmax of 2180 ng/ml and an AUCi of 2007 ng·h/ml. Co-administration of robenacoxib non-flavoured tablets with food produced no delay in Tmax, but slightly lower values for Cmax and AUC. The systemic bioavailability of robenacoxib tablets in dogs was 62% with food and 84% without food. Robenacoxib has a relatively small volume of distribution (Vss 240 ml/kg) and is highly bound to plasma proteins (>99%). Robenacoxib is extensively metabolised by the liver in dogs. Apart from one lactam metabolite, the identity of other metabolites is not known in dogs. Robenacoxib is cleared rapidly from blood (CL 0.81 L/kg/h) with an elimination t1/2 of 0.7 h after intravenous administration. After oral administration of the tablets, the terminal half-life in blood was 0.91 h. Robenacoxib persists longer and at higher concentrations at sites of inflammation than in blood. Robenacoxib is excreted predominantly via the biliary route (~65%) and the remainder via the kidneys. Repeated oral administration of robenacoxib to dogs at dosages of 2-10 mg/kg for 6 months produced no change in the blood profile, with neither accumulation of robenacoxib nor enzyme induction. Accumulation of metabolites has not been tested. The pharmacokinetics of robenacoxib do not differ between male and female dogs, and are linear over the range 0.5-8 mg/kg.
Shelf life
Shelf life of the veterinary medicinal product as packaged for sale: 2 years.
Special precautions for storage
Do not store above 30 °C. Store in the original package in order to protect from moisture.
Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products
Medicines should not be disposed of via wastewater. Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements.