Abstract
The present study was undertaken to examine whether the pharmacokinetic and pharmacodynamic alterations of S-1452, a new thromboxane A2 (TXA2) receptor antagonist, occur with a repeated administration. Fifty mg of S-1452 was given orally, twice a day for 8 days in 5 healthy subjects. Blood samples for determination of plasma drug concentration and its effect on platelet aggregation ex vivo were taken after the 1st and 15th administrations. S-1452 was rapidly absorbed with a plasma peak at 0.8 hour after the 1st and at 1.1 hour after the 15th administration. Thereafter, the drug was rapidly eliminated (mean elimination half-life: 0.5 hour after the 1st and 15th administrations). No significant difference was observed in any pharmacokinetic parameter between the 1st and 15th administrations. The inhibition of U-46619-induced platelet aggregation (a TXA2 receptor agonist) persisted up to 9 hours after the 1st and 15th administrations. The effect after the 15th administration was significantly greater than that after the 1st administration. These results suggest that although the pharmacokinetic alteration of S-1452 is negligible, its inhibitory effect on platelet aggregation is enhanced with a repeated treatment.
