Received for publication January 8, 2007.
Revised March 28, 2007.
Accepted for publication March 29, 2007.

The Disposition of Prasugrel, a Novel Thienopyridine, in Humans

Abstract

Prasugrel, a prodrug, is a novel and potent inhibitor of platelet aggregation in vivo. The metabolism of prasugrel and the elimination and pharmacokinetics of its active metabolite, R-138727, three inactive metabolites, and radioactivity were determined in five healthy male subjects after a single 15 mg (100 µCi) oral dose of [¹⁴C]prasugrel. Prasugrel was rapidly absorbed and maximum plasma concentrations of radioactivity and R-138727 were achieved in 30 min, indicating rapid formation of R-138727. Prasugrel was extensively metabolized in humans, first by hydrolysis to a thiolactone, followed by ring opening to form R-138727, which was further metabolized by S-methylation and conjugation with cysteine. Total radioactivity was higher in plasma than in blood, suggesting limited penetration of prasugrel metabolites into red blood cells. Approximately 70% of the dose was excreted in the urine and 25% in the feces.

Key words: drug disposition, excretion, half-life, human pharmacokinetics, metabolite identification, metabolite kinetics, prodrugs

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