Prasugrel (CS-747, LY640315), a novel thienopyridine, is a potent and orally active antiplatelet agent in vivo. The aims of this double-blind, double-dummy, placebo-controlled, randomized, parallel group phase 1 study were to investigate the antiplatelet effects of prasugrel after oral administration of a loading dose (LD) and subsequent 20 days of once-daily maintenance dosing (MD), to characterize the pharmacokinetics of prasugrel metabolites with an LD/MD regimen, and to assess the safety and tolerability of prasugrel in healthy subjects. Subjects were randomly assigned in a 1:1:1 ratio to prasugrel 40 mg LD/7.5 mg MD (n=11), prasugrel 60 mg LD/15 mg MD (n=10), or placebo LD/placebo MD (n=11). Prasugrel 40 and 60 mg LDs provided rapid and consistent inhibition of 20 μM adenosine diphosphate (ADP)-stimulated platelet aggregation. Prasugrel 7.5 and 15 mg MDs maintained inhibition in a dose-dependent manner. The pharmacokinetic data indicate that exposure to prasugrel metabolites occurs rapidly after dosing and is consistent with dose proportionality. Within the limitations of this study, the safety and tolerability results suggest that prasugrel is well tolerated when dosed as an initial LD followed by a lower daily MD for 20 days. Prasugrel LDs and MDs provide rapid and sustained inhibition of ADP-mediated platelet aggregation.