EFFECT OF FOOD-INTAKE ON PHARMACOKINETICS AND EFFECTS OF A NEW THROMBOXANE A(2) RECEPTOR ANTAGONIST, S-1452

Objective: To examine the effect of food ingestion on the pharmacokine tics of a new thromboxane A(2) (TXA(2)) receptor antagonist, S-1452, a nd the inhibitory effect on platelet aggregation. Methods: Fifty milli grams of S-1452 was given orally to eight healthy subjects with or wit hout food. Blood samples for determinations of plasma drug concentrati ons and of its effects on platelet aggregation were taken for a 12-h p ost-drug period. Results: The maximum plasma concentration of S-1452 w as reduced by 47% and the time to maximum concentration was prolonged from 0.5 to 1.9 h after dosing with food. The inhibitory effect of S-1 452 on platelet aggregations induced by U-46619, a TXA(2) receptor ago nist, and collagen persisted up to 9 h after dosing with and without f ood. The degrees of inhibition in the two trials did not differ signif icantly at any point. Conclusion: These results suggest that although the absorption of S-1452 is delayed and, consequently, its plasma conc entration is decreased after dosing with food, the inhibitory effect o n platelet aggregation is not significantly influenced after 50 mg of the drug.