Pharmacotherapeutic group: Antiinflammatory and antirheumatic products, non-steroids.
ATCvet code: QM01AH91
Pharmacodynamics
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 cats, using an in vitro whole blood assay, robenacoxib was approximately 500 fold selective for COX-2 (IC50 0.058 μM) as compared to COX-1 (IC50 28.9 μM). In vivo, robenacoxib solution for injection produced marked inhibition of COX-2 activity and had no effect on COX-1 activity. At the recommended dosage (2 mg/kg), analgesic, anti-inflammatory and anti-pyretic effects were demonstrated in an inflammation model, and in clinical trials, robenacoxib reduced pain and inflammation in cats undergoing orthopaedic or soft tissue surgery.
In dogs, robenacoxib was in vitro approximately 140 fold selective for COX-2 (IC50 0.04 μM) as compared to COX-1 (IC50 7.9 μM). In vivo, robenacoxib solution for injection produced marked inhibition of COX-2 activity and had no effect on COX-1 activity. At dosages ranging from 0.25 to 4 mg/kg, robenacoxib had analgesic, antiinflammatory and anti-pyretic effects in an inflammation model with a rapid onset of action (1 h). In clinical trials at the recommended dose (2 mg/kg), robenacoxib reduced pain and inflammation in dogs undergoing orthopaedic or soft tissue surgery, and reduced the need for rescue treatment in dogs undergoing soft tissue surgery.
Pharmacokinetics
Cats:
Absorption
Peak blood concentrations of robenacoxib are attained rapidly after subcutaneous injection.
After a dosage of 2 mg/kg a Tmax of 1 h, a Cmax of 1,464 ng/ml and an AUC of 3,128 ng·h/ml is obtained. After a subcutaneous administration of 1 mg/kg the systemic bioavailability is 69%.
Distribution
Robenacoxib has a relatively small volume of distribution (Vss of 190 ml/kg) and is highly bound to plasma proteins (>99%).
Biotransformation
Robenacoxib is extensively metabolised by the liver. Apart from one lactam metabolite, the identity of other metabolites is not known.
Elimination
After intravenous administration robenacoxib was rapidly cleared from blood (CL of 0.44 L/kg/h) with an elimination t1/2 of 1.1 h. After subcutaneous administration, the terminal half-life from blood was 1.1 h.
Robenacoxib persists longer and in higher concentrations at sites of inflammation than in blood.
Robenacoxib is excreted predominantly via the biliary route (∼70%) and the remainder via the kidneys. Repeated subcutaneous administration at dosages of 2– 20 mg/kg produced no change in the blood profile, with neither bioaccumulation of robenacoxib nor enzyme induction. Bioaccumulation of metabolites has not been tested. The pharmacokinetics of robenacoxib injection do not differ between male and female.
Dogs:
Absorption
Peak blood concentrations of robenacoxib are attained rapidly after subcutaneous injection. After a dosage of 2 mg/kg a Tmax of 1 h, a Cmax of 615 ng/ml and an AUC of 2,180 ng·h/ml is obtained. After a subcutaneous administration of 1 mg/kg the systemic bioavailability is 88%.
Distribution
Robenacoxib has a relatively small volume of distribution (240 ml/kg) and is highly bound to plasma proteins (>99%).
Biotransformation
Robenacoxib is extensively metabolised by the liver. Apart from one lactam metabolite, the identity of other metabolites is not known.
Elimination
After intravenous administration robenacoxib was rapidly cleared from blood (CL of 0.81 L/kg/) with an elimination t1/2 of 0.8 h. After subcutaneous administration, the terminal half-life from blood was 1.2 h.
Robenacoxib persists longer and in 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 subcutaneous administration at dosages of 2– 20 mg/kg produced no change in the blood profile, with neither bioaccumulation of robenacoxib nor enzyme induction. Bioaccumulation of metabolites has not been tested. The pharmacokinetics of robenacoxib injection do not differ between male and female, and are linear over the range of 0.25–4 mg/kg.
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Use take-back schemes for the disposal of any unused veterinary medicinal product or waste materials derived thereof in accordance with local requirements and with any national collection systems applicable to the veterinary medicinal product concerned.