Key result
In elderly subjects, a single 10 mg dose of S-1452 resulted in a lower metabolite to unchanged compound ratio (1.1 vs 1.7) and prolonged platelet aggregation inhibition compared to young subjects.
Why the study?
Does age affect the pharmacokinetics and platelet aggregation inhibitory effect of a single 10 mg oral dose of the thromboxane A2 receptor antagonist S-1452 in male subjects?
RCT (n=16)
Single-blind
Randomized
No
Does age affect the pharmacokinetics and platelet aggregation inhibitory effect of a single 10 mg oral dose of the thromboxane A2 receptor antagonist S-1452 in male subjects?
Absolute Event Rate: 1.1% vs 1.7%
p-value: p=<0.05
A single 10 mg oral dose of the thromboxane A2 receptor antagonist S-1452 results in higher plasma concentrations and prolonged inhibition of platelet aggregation in elderly compared to young male subjects.
Warrants caution with S-1452 dosing or monitoring in elderly; extends age-stratified PK/PD data for thromboxane antagonists.
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.
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Fujimura et al. (1997) conducted an RCT in Healthy volunteers and elderly subjects (n=16). S-1452 vs. Young subjects was evaluated on Ratio of metabolites to unchanged compound in Cmax (p=<0.05). In elderly subjects, a single 10 mg dose of S-1452 resulted in a lower metabolite to unchanged compound ratio (1.1 vs 1.7) and prolonged platelet aggregation inhibition compared to young subjects.
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