EFFECTS ON PLATELET FUNCTIONS AND PHARMACOKINETICS OF AZAPROPAZONE AND KETOROLAC TROMETHAMINE GIVEN AS SINGLE PARENTERAL DOSES

1 Thee biosynthesis of thromboxane (TX) B2 and immunoreactive prostaglandin (PG) F2alpha in clotting whole blood ex vivo as well as collagen-induced platelet aggregation were determined before and up to 72 h after intravenous injection of 600 mg azapropazone 2H2O and intramuscular injection of 30 mg ketorolac tromethamine in six healthy subjects. The drug doses were selected on the basis of comparable analgesic activity (maximal recommended analgesic dose). 2 Both platelet aggregation and prostanoid biosynthesis were inhibited by racketorolac to a significantly greater extent and for a longer period of time than by azapropazone. 3 Correlations between serum concentrations and the inhibitory effects on TXB2 biosynthesis were observed for both drugs. Using the sigmoidal E(max) model the mean serum concentration of azapropazone inhibiting platelet TXB2 generation by 50% (EC50) was found to be 98.1 +/- 41.9 (s.d.) mug ml-1, a value 1000 times higher than that for rac-ketorolac. 4 Tie moderate inhibition of platelet function by azapropazone as compared with rac-ketorolac might be an advantage with regard to its use as a post-operative analgesic.