Effect of various doses of acetylsalicylic acid in combination with dipyridamole on the balance between prostacyclin and thromboxane in human serum.
1 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 F1 alpha (6-keto-PGF1 alpha) and TxB2 respectively, were measured in serum with specific radioimmunoassays before and 1 and 3 h afer the ingestion of the test dose. 3 The basal concentrations of 6-keto-PGF1 alpha and TxB2 correlated significantly (r = 0.588, P less than 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 alpha 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.
D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D004176:Dipyridamole / Q000494:pharmacology*; D011464:Epoprostenol / Q000097:blood*; D005260:Female; D006801:Humans; D008875:Middle Aged; D011453:Prostaglandins / Q000097:blood*; D011461:Prostaglandins F, Synthetic / Q000097:blood; D013931:Thromboxanes / Q000097:blood*; D013997:Time Factors
D011453:Prostaglandins; D011461:Prostaglandins F, Synthetic; D013931:Thromboxanes; D004176:Dipyridamole; D011464:Epoprostenol; D001241:Aspirin