抄録
The effect of age on the pharmacokinetics of a new thromboxane A2 (TXA2) receptor antagonist, S-1452, and the inhibitory effect on platelet aggregation were examined in young (24-31 years, n=8) and elderly (68-78 years, n=8) male subjects. Ten mg of S-1452 or placebo was given orally in a single-blind cross-over design.
Hepatic function estimated by indocyanine green (ICG) test decreased in the elderly [elimination rate constant of ICG; elderly: 0.161 (mean) vs. young: 0.192/min, p<0.05]. The maximum plasma concentration of S-1452 tended to be greater in the elderly than in the young [elderly: 28.7 (mean), young: 16.4 neml]. The ratio of the metabolites to unchanged compound in the Cmax was significantly lower in the elderly than in the young [elderly: 1.1 (mean) vs. young: 1.7, p<0.05]. The inhibitory effect of S-1452 on platelet aggregation ex vivo induced by U-46619, a TXA2 receptor agonist, persisted up to 6 and 9 hours after dosing in the young and elderly subjects, respectively.
These results suggest that the plasma concentration of S-1452 is higher, probably due to the reduced conversion of S-1452 to the metabolites, and the inhibition on platelet aggregation is prolonged in the elderly.
