Effect of the Infusion of OKY-046, a Thromboxane A₂ Synthase Inhibitor, on Urinary Metabolites of Prostacyclin and Thromboxane A₂ in Healthy Human Subjects

Summary

The influence of OKY-046, a selective thromboxane synthase inhibitor, on prostanoid formation in healthy human subjects was studied. Vehicle (5% glucose solution) or OKY-046 in 5% glucose solution at 15 μg kg⁻¹ min⁻¹ was intravenously administered to five male healthy volunteers for 6 h. Platelet aggregation and thromboxane B₂ (TXB₂) formation induced by collagen and arachidonic acid were suppressed by the infusion of OKY-046, while both were not affected by the infusion of vehicle. Urinary excretion of 11-dehydro-thromboxane B₂, one of major urinary metabolites of thromboxane A₂ (TXA₂) was decreased by the infusion of OKY-046, while that of 2,3-dinor-6-keto-prostaglandin F_1α, one of major urinary metabolites of prostacyclin (PGI₂) was increased. The present study demonstrated that the infusion of OKY-046 improved the balance of TXA₂/PGI₂ into antithrombotic state in healthy subjects. It was also suggested that endogenously produced (probably platelet-derived) endoperoxides could be redirected into prostacyclin in vivo.

• References

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