ATC Vet Code: QM01AH92

Mavacoxib is a non-steroidal anti-inflammatory drug (NSAID) of the coxib class. Mavacoxib is 4-[5-(4-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-benzenesulfonamide. It is a diarylsubstituted pyrazole. The principal mode of action is inhibition of cyclooxygenase (COX).

COX is a key enzyme in pathways of arachidonic acid metabolism. Its activity culminates in the synthesis of local hormones and inflammatory mediators, termed eicosanoids, which include several prostaglandins. There are two isoforms of COX, COX-1, and COX-2. COX-1 is a widely distributed constitutive enzyme, primarily involved in maintaining organ and tissue function, whilst COX-2 is inducible at sites of tissue damage but in some organs, it is also constitutive. COX-2 exerts the major role in synthesising prostaglandins which have pivotal roles as mediators of pain, inflammation and fever. Mavacoxib acts by preferential inhibition of COX-2-mediated prostaglandin synthesis. It therefore possesses analgesic and anti-inflammatory properties. The products of COX-2 metabolism are also involved in ovulation, implantation and closure of the ductus arteriosus. Both COX-1 and COX-2 are present constitutively in the kidney and are assumed to possess protective roles in adverse physiological circumstances.

Based on the results of canine whole blood assays, plasma concentrations producing 20% COX-1 inhibition and 80% COX-2 inhibition were 2.46 µg/mL and 1.28 µg/mL, respectively, so that the IC20COX-1:IC80COX-2 potency ratio is approximately 2:1, whilst the IC80COX-1:IC80COX-2 potency ratio is approximately 40:1. These IC concentrations may be compared with mean trough concentrations of mavacoxib in plasma in clinical subjects of 0.52 and 1.11 µg/mL, respectively, after the first and fifth doses. Therefore, clinical doses are predicted to produce low level inhibition of COX-1 and high-level inhibition of COX-2.

Mavacoxib is well absorbed after oral administration; bioavailability was 87% in fed dogs and 46 % in fasted conditions and the recommended dose is based on administration with food. Therapeutic concentrations in fed dogs are reached rapidly and peak concentrations are obtained in less than 24 hours after administering a dose. Mavacoxib is approximately 98% bound to plasma proteins. It is extensively distributed throughout the body and almost all the mavacoxib-related residues in plasma comprise parent drug. The rate of body clearance of mavacoxib is slow and the major route of elimination is by biliary excretion of the parent drug.

Multiple-dose pharmacokinetic studies provided no evidence that mavacoxib produces autoinhibition or autoinductive changes in its clearance, and it exhibits linear pharmacokinetics with oral doses ranging from 2 to 50 mg/kg. In laboratory studies with young adult dogs, mean elimination half-life values ranged from 13.8 to 19.3 days. Mavacoxib possessed a longer elimination half-life in client-owned animals. Population pharmacokinetic data derived from studies in dogs with a predominantly older population with heavier dogs as compared to the experimental studies (mean 9 years of age) showed that the mean elimination half-life was 39 days with a small sub-population (<5%) having an elimination half-life of more than 80 days and correspondingly an increased exposure was recorded in these individuals. The reason for this longer half-life is unknown. Steady state pharmacokinetics was attained by the fourth treatment in most animals.