Effect of Various Doses of Acetylsalicylic Acid in Combination With Dipyridamole on the Balance Between Prostacyclin and Thromboxane in Human Serum

Abstract

I Thirty-six healthy human subjects were randomly divided into six groups which were treated with a single dose of 75 mg (1.3 mg/kg) of dipyridamole alone, or 75 mg of dipyridamole in combination with 30 mg (0.5 mg/kg), 50 mg (0.8 mg/kg), 160 mg (2.6 mg/kg) and 330 mg (5.7 mg/kg) of acetylsalicylic acid (ASA), or with placebo. 2 The concentrations of prostacyclin (PGI2) and thromboxane A2 (TxA2) metabolites, 6-keto-prostaglandin Fl, ) and TxB2 respectively, were measured in serum with specific radioimmunoassays before and 1 and 3 h after the ingestion of the test dose.3 The basal concentrations of 6-keto-PGF1, and TxB2 correlated significantly (r = 0.588, P < 0.001). 4 Dipyridamole alone did not change PGI2 or TxA2 production. 5 Dipyridamole-ASA combinations with ASA doses between 0.5 and 0.8 mg/kg inhibited TxB2 production by 48 to 74%, and with the ASA doses between 2.6 and 5.7 mg/kg by about 90%. None of these combinations changed PGI2 production. 6 The ratio of 6-keto-PGF1, to TxB2 increased 3.5 to 6 times with ASA doses of 0.5 to 0.8 mg/kg and 21 to 29 times with doses between 2.6 to 5.7 mg/kg. 7 These results suggest that the anti-thrombotic effect of dipyridamole in vivo is not mediated through direct changes in PGI2 and/or TxA2 production.

The Effect of a Thromboxane Synthetase Inhibitor, Dazoxiben, and Acetylsalicylic Acid on Platelet Function and Prostaglandin Metabolism

“…Since 0.25 g prevented PGI2 production almost completely, a possible selevtive effect must be sought in lower doses. Thus, a single dose lower than 50 mg may reduce TxA2 production more than the generation of PGI2 (23, 24), but then only a weak inhibition of platelet cyclo-oxygenase is achieved (25,26), and the effect on platelet behaviour will most probably be small.…”