EVALUATION OF SELECTIVE-INHIBITION OF CANINE CYCLOOXYGENASE-1 AND CYCLOOXYGENASE-2 BY CARPROFEN AND OTHER NONSTEROIDAL ANTIINFLAMMATORY DRUGS

Objective-To evaluate the activity of carprofen and other nonsteroidal anti-inflammatory drugs (NSAID) against isozymes of canine cyclooxyge nases (COX1 and COX2). Procedure-Constitutive COX1 was obtained from w ashed canine platelets, and COX2 was obtained from a canine macrophage -like cell line that was induced with endotoxin. Activity of carprofen and other NSAID against COX1 and COX2 was compared. Dose-response cur ves were plotted, and calculations were performed to identify concentr ations that caused 50% inhibition (IC50 [mu M]) for each isozyme. Rati o of the COX1-to-COX2 IC50 was used as a measure of isozyme selectivit y. Results-Of the compounds evaluated, carprofen had the greatest sele ctivity for COX2. Potency of carprofen for canine COX2 was more than 1 00-fold greater than for canine COX1. Inhibition of canine COX2 (IC50, 0.102 CIM) for the racemic mixture of carprofen (S and R stereoisomer s) was primarily attributable to the S enantiomer (IC50, 0.0371 mu M), which was approximately 200-fold more potent than the R enantiomer (I C50, 5.97 mu M). Nimesulide had the next highest selectivity for COX2 (38-fold), and tolfenamic acid and meclofenamic acid had 15-fold selec tivity for COX2. The other compounds tested did not have substantial s electivity for canine COX2 or were more selective for canine COX1. Con clusions-Carprofen was found to be a potent inhibitor of canine COX2. Of the compounds tested, carprofen had the highest selectivity for can ine COX2. Clinical Relevance-The selectivity of carprofen for canine C OX2 may be an important factor for its use in dogs.