Effect of the infusion of OKY-046, a thromboxane A2 synthase inhibitor, on urinary metabolites of prostacyclin and thromboxane A2 in healthy human subjects.
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 micrograms 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 F1 alpha, 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.
Morio
H
H
Second Department of Internal Medicine, Chiba University Medical School, Japan.
Hirai
A
A
Terano
T
T
Tamura
Y
Y
Yoshida
S
S
D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives* / Q000652:urine; D000328:Adult; D011464:Epoprostenol / Q000378:metabolism*; D006801:Humans; D008297:Male; D008689:Methacrylates / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D013928:Thromboxane A2 / Q000378:metabolism*; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D008689:Methacrylates; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; C049235:11-dehydro-thromboxane B2; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; C034364:ozagrel