PHARMACOKINETICS OF A NEW THROMBOXANE A(2) RECEPTOR ANTAGONIST, S-1452, AND ITS EFFECT ON PLATELET-AGGREGATION IN HEALTHY-VOLUNTEERS

To study the pharmacokinetics of a new thromboxane A(2) (TXA(2)) recep tor antagonist, S-1452, eight healthy volunteers were given placebo or S-1452 orally on four occasions in step-wise increasing doses of 10 m g, 25 mg, and 50 mg separated by a-week intervals. Blood samples for m easurement of plasma concentrations of the drug and of its inhibitory effect on platelet aggregation were obtained for 24 hours after admini stration. Bleeding time after administration was measured. S-1452 was rapidly absorbed, with a peak plasma concentration at 30 minutes after administration. Thereafter, the drug was rapidly eliminated (eliminat ion half-life, 0.4-0.5 hours), and no drug was detected at 6 hours. Th e inhibitory effect of S-1452 on platelet aggregation, which was stimu lated by the TXA(2) receptor agonist U-46619, persisted more than 6 ho urs after drug administration. Bleeding time was slightly prolonged af ter a single dose of S-1452. These results suggest that although S-145 2 is rapidly eliminated in plasma, its inhibitory effects on platelet aggregation persist for a longer period. Careful observations are need ed to prevent potential bleeding episodes during repeated treatment wi th the drug.