EFFECT OF OKY-046, A SELECTIVE THROMBOXANE INHIBITOR, ON PROSTAGLANDIN PRODUCTION AND FUNCTION OF PREGNANT RAT UTERI AND PLATELETS

The effect of OKY-046 (ONO, Japan), a selective TX inhibitor, was studied for it''s effect on uterine and platelet activity. On day 21 of pregnancy, rats were injected with either 0, 1, or 5 mg/kg OKY-046 via the tail vein. One hour following injections, in vitro activity of uteri and platelets was assessed. A decrease (P < .01) in uterine TXB2 production (measured by RIA) occurred with increasing OKY-046 dose (104 .+-. 31 vs 44 .+-. 6 vs 24 .+-. 2 ng TXB2/g tissue/45 min). OKY-046 treatment had no effect on other prostanoids. Contractile activity was not affected by OKY-046. The amount of TXB2 produced in platelets from OKY-046 (5 mg/kg) treated rats was 45.5% less than that from controls (P < 0.001). Likewise, arachidonate-induced aggregation of platelets from OKY-046 treated rats was 46.1% less (P < .05) than that of controls. In summary, in vivo administration of OKY-046 selectively reduced uterine TXB2 without altering other prostanoids, or affecting uterine contractions. In contrast, both platelet TXB2 production and platelet function (aggregation) was decreased.