Evaluation of the Pharmacokinetics and Pharmacodynamics of Prasugrel in Japanese Elderly Subjects

Abstract

Background and Objective

An increased incidence in bleeding events has been reported in Western elderly patients receiving prasugrel. Therefore, doses in Japanese elderly subjects need to be carefully determined. We assessed the pharmacokinetic and pharmacodynamic effects of prasugrel at the clinical dose used in Japan in healthy Japanese elderly subjects compared with non-elderly subjects.

Methods

In an open-label parallel-group study conducted in Japan, two groups (elderly, aged >75 years; non-elderly, aged 45–65 years) received a 20-mg loading dose and a 3.75-mg maintenance dose of prasugrel for 7 days. Plasma concentration of its active metabolite, R-138727, and pharmacokinetic parameters were determined on days 1 and 7 after dosing. Pharmacodynamic response to 20 µM of adenosine diphosphate-induced platelet aggregation was measured by light transmission aggregometry.

Results

A total of 47 subjects were enrolled (23 elderly, 24 non-elderly). There was no statistically significant difference in pharmacokinetic parameters between groups: area under the plasma concentration–time curve up to the last quantifiable time and maximum plasma concentration were about 174–175 ng·h/mL and 134–153 ng/mL, respectively, after the loading dose; and about 25–26 ng·h/mL and 25 ng/mL, respectively, after the maintenance dose. Inhibition of platelet aggregation was higher in the elderly subjects than in the non-elderly subjects, with a statistically significant difference from 24 h after the loading dose. No serious adverse events (bleeding or non-bleeding) occurred.

Conclusions

Prasugrel (20-mg loading dose; 3.75-mg maintenance dose) produced a slight increase in antiplatelet efficacy in elderly compared with non-elderly subjects, despite no statistically significant difference in the pharmacokinetics.

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