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

Summary

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-PGF_1α rose. The larger dose of ASA reduced both TxB₂ and 6-keto-PGF_1α in plasma. Whole blood was allowed to clot in order to estimate prostaglandin metabolism. Both drugs prevented thromboxane production effectively. Formation of 6-keto-PGF_1α 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.

Keywords

Thromboxane synthetase inhibition - Cyclo-oxygenase inhibition - Thromboxane - Prostacyclin - Platelet function

• References

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