Effects on platelet functions and pharmacokinetics of azapropazone and ketorolac tromethamine given as single parenteral doses.
The biosynthesis of thromboxane (TX) B2 and immunoreactive prostaglandin (PG) F2 alpha 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). 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. Correlations between serum concentrations and the inhibitory effects on TXB2 biosynthesis were observed for both drugs. Using the sigmoidal Emax model the mean serum concentration of azapropazone inhibiting platelet TXB2 generation by 50% (EC50) was found to be 98.1 +/- 41.9 (s.d.) micrograms ml-1, a value 1000 times higher than that for rac-ketorolac. The 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.
Department of Pharmacology and Toxicology, Ruhr-University, Bochum, Germany.
D
D
Pallapies
B A
BA
Peskar
K
K
Brune
G
G
Geisslinger
D000328:Adult; D000700:Analgesics / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001032:Apazone / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003094:Collagen / Q000494:pharmacology; D015237:Dinoprost / Q000096:biosynthesis; D004338:Drug Combinations; D006207:Half-Life; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D020911:Ketorolac Tromethamine; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000097:blood; D014046:Tolmetin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D014325:Tromethamine / Q000493:pharmacokinetics / Q000494:pharmacology*
D000700:Analgesics; D004338:Drug Combinations; D010975:Platelet Aggregation Inhibitors; D014325:Tromethamine; D020911:Ketorolac Tromethamine; D013929:Thromboxane B2; D003094:Collagen; D015237:Dinoprost; D014046:Tolmetin; D001032:Apazone