Effect of food intake on pharmacokinetics and effects of a new thromboxane A2 receptor antagonist, S-1452

Abstract

Objective: To examine the effect of food ingestion on the pharmacokinetics of a new thromboxane A₂ (TXA₂) receptor antagonist, S-1452, and the inhibitory effect on platelet aggregation.

Methods:

Fifty milligrams of S-1452 was given orally to eight healthy subjects with or without food. Blood samples for determinations of plasma drug concentrations and of its effects on platelet aggregation were taken for a 12-h post-drug period.

Results:

The maximum plasma concentration of S-1452 was 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-1452 on platelet aggregations induced by U-46619, a TXA₂ receptor agonist, and collagen persisted up to 9 h after dosing with and without food. The degrees of inhibition in the two trials did not differ significantly at any point.

Conclusion:

These results suggest that although the absorption of S-1452 is delayed and, consequently, its plasma concentration is decreased after dosing with food, the inhibitory effect on platelet aggregation is not significantly influenced after 50 mg of the drug.