The effect of oral administration of dipyrone on the capacity of blood platelets to synthesize thromboxane A2 in man.

Platelet aggregation and thromboxane A2 (TXA2) production induced by arachidonic acid and collagen were studied in 10 healthy volunteers prior to and at various times after the oral administration of a single dose of 1 g dipyrone. The plasma concentrations of four dipyrone metabolites were also determined. Dipyrone inhibited platelet aggregation and markedly decreased TXA2 synthesis induced by threshold concentrations of both agonists. Maximal inhibition was noted 1 hour after drug administration and in some subjects it lasted as long as 72 h. At all times the effect of the drug could be abolished by increasing the concentration of the agonist. This is consistant with a competitive inhibitory effect of dipyrone on prostaglandin synthetase activity. The mean plasma concentration of the main dipyrone metabolite methylaminoantipyrine at 1 h was 11 micrograms/ml. There was no correlation between individual plasma levels and the parameters of platelet function. At 24h the mean concentration of each of the metabolites studied was up to 1 microgram/ml, and these levels, too, did not correlate with the biological effect of the drug.