The effect of a thromboxane synthetase inhibitor, dazoxiben, and acetylsalicylic acid on platelet function and prostaglandin metabolism

Thromb Haemost. 1983 Oct 31;50(3):703-6.

Abstract

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial

MeSH terms

  • 6-Ketoprostaglandin F1 alpha / blood
  • Adult
  • Aged
  • Aspirin / pharmacology*
  • Blood Platelets / drug effects*
  • Humans
  • Imidazoles / pharmacology*
  • Male
  • Middle Aged
  • Oxidoreductases / antagonists & inhibitors*
  • Platelet Adhesiveness / drug effects
  • Platelet Aggregation / drug effects
  • Prostaglandins / metabolism*
  • Thromboxane B2 / blood
  • Thromboxane-A Synthase / antagonists & inhibitors*

Substances

  • Imidazoles
  • Prostaglandins
  • dazoxiben
  • Thromboxane B2
  • 6-Ketoprostaglandin F1 alpha
  • Oxidoreductases
  • Thromboxane-A Synthase
  • Aspirin