The effect of a thromboxane synthetase inhibitor, dazoxiben, and acetylsalicylic acid on platelet function and prostaglandin metabolism.
Twenty-four men received either placebo, 0.1 g of the thromboxane synthetase inhibitor dazoxiben, 0.25 or 1.0 g of acetylsalicylic acid (ASA). Dazoxiben reduced the maximal rate of collagen-induced platelet aggregation, but less than did ASA. ASA abolished secondary, ADP-induced aggregation, dazoxiben not. Both drugs prolonged the bleeding-time. Plasma thromboxane B2 (TxB2) levels did not change significantly after dazoxiben, whereas the prostacyclin metabolite 6-keto-PGF1 alpha rose. The larger dose of ASA reduced both TxB2 and 6-keto-PGF1 alpha in plasma. Whole blood was allowed to clot in order to estimate prostaglandin metabolism. Both drugs prevented thromboxane production effectively. Formation of 6-keto-PGF1 alpha decreased by 95 per cent after ASA but was more than doubled after dazoxiben. Dazoxiben is a selective and effective thromboxane synthetase inhibitor, but has a weaker effect on platelet reactivity than ASA, possibly because endoperoxide formation is not prevented.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000328:Adult; D000368:Aged; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011453:Prostaglandins / Q000378:metabolism*; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D011453:Prostaglandins; C029166:dazoxiben; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D010088:Oxidoreductases; D013930:Thromboxane-A Synthase; D001241:Aspirin