Characterization of the Analgesic and Anti-Inflammatory Activities of Ketorolac and Its Enantiomers in the Rat

The marked analgesic efficacy of ketorolac in humans, relative to other nonsteroidal anti-inflammatory drugs (NSAIDs), has lead to speculation as to whether additional non-NSAID mech-anism(s) contribute to its analgesic actions. To evaluate this possibility, we characterized (R,S)-ketorolac’s pharmacological properties in vivo and in vitro using the nonselective cycloox-ygenase (COX) inhibitors [indomethacin (INDO) and diclofenac sodium (DS)] as well as the selective COX-2 inhibitor, celecoxib, as references. The potency of racemic (R,S)-ketorolac was similar in tests of acetic acid-induced writhing, carrageenan-induced paw hyperalgesia, and carrageenan-induced edema formation in rats; ID50 values 5 0.24, 0.29, and 0.08 mg/kg, respectively. (R,S)-ketorolac’s actions were stereospecific, with (S)-ketorolac possessing the biological activity of the racemat