Summary
The pharmacokinetics and effects on platelet function of dipyrone (1.0 g; 2.5 g; i.
v.) and ketorolac tromethamine (30 mg; i.m.) were studied in a three-way crossover
study in twelve healthy subjects. The biosynthesis of thromboxane A2 in clotting whole
blood ex vivo as well as collagen-induced platelet aggregation were determined before
and up to 48 h after administration. Both prostanoid biosynthesis and platelet aggregation
were inhibited by ketorolac tromethamine for a significantly longer period of time
than by both doses of dipyrone. The changes in platelet functions correlated well
with the serum concentrations of ketorolac or 4-methylaminoantipyrine and 4-aminoantipyrine.
Using the sigmoidal Emax model the mean serum concentration (SD) of ketorolac, 4-methylaminoantipyrine and
4-aminoantipyrine inhibiting platelet TXB2 generation by 50% (EC50) in vitro was found to be 0.088 ± 0.031, 1.2 ± 0.3 and 10.2
± 3.4 µg ml-1, respectively. In conclusion the recovery of platelet function after dipyrone administration
is faster as compared to ketorolac tromethamine. This is in line with clinical observations
and may be an advantage when these drugs are given as postoperative analgesics at
the doses tested.
