COMPARISON OF KETOROLAC TROMETHAMINE WITH OTHER INJECTABLE NONSTEROIDAL ANTIINFLAMMATORY DRUGS FOR PAIN-ON-INJECTION AND MUSCLE DAMAGE IN THE RAT

The local tolerance of ketorolac tromethamine (Toradol(R), Syntex) was compared with that of four other injectable nonsteroidal anti-inflamm atory drugs (NSAIDs) (diclofenac sodium, piroxicam, ketoprofen, and me tamizol magnesium) in the rat paw-lick/muscle irritation assay as desc ribed previously.(1) All drugs were tested at concentrations approved for clinical use, After subplantar (footpad) injection, ketorolac prod uced virtually no pain-on-injection as assessed by the number of paw-l ick/lift responses during a 15 min observation period. The other NSAID s produced slight to moderate paw-lick/lift responses. Redness and swe lling at the injection site were less severe for ketorolac than for th e other NSAIDs. After intramuscular (i.m.) injection, all of the NSAID s produced some degree of muscle damage, as assessed histopathological ly 24 h after injection. The lesions, consisting primarily of muscle d egeneration, were less severe for ketorolac than for the other NSAIDs. Ketorolac and metamizol produced the smallest elevations in serum cre atine kinase, as measured 2 h after i.m. dosing, not significantly dif ferent from isotonic saline. Overall, ketorolac was better tolerated i n the assay than the other injectable NSAIDs, thereby suggesting the p ossibility of improved local tolerance on clinical use.