RESUMO
We assessed the tolerability, pharmacodynamics as measured by inhibition of platelet aggregation (IPA), and pharmacokinetics of prasugrel (CS-747, LY640315), a novel thienopyridine antiplatelet agent in healthy volunteers. Twenty-four subjects were randomized into four groups of six in a double-blind, placebo-controlled trial. One subject in each group received placebo and five subjects received prasugrel orally at single doses of 2.5, 10, 30, or 75 mg. The IPA, assessed using 5 and 20 microM ADP, was periodically measured over a 7-day period by light transmission aggregometry. Plasma concentrations for three major metabolites, R-95913, R-106583, and R-100932, were measured. There were no serious adverse events and no clinically significant changes noted in any laboratory or clinical evaluations in any subject. At 1 h after prasugrel 30 and 75 mg, platelet aggregation induced by 20 microM ADP was inhibited by 43.5 +/- 7.8 and 43.2 +/- 15.7%, respectively, and this inhibition was significantly greater than that following placebo (5.9 +/- 3.5%) (P < 0.05 for both doses). The degree of inhibition observed at 2 h was slightly higher with both prasugrel 30 and 75 mg (59.8 +/- 9.9 and 57.0 +/- 7.2%) and was maintained through the subsequent 22 h. At 24 h, maximal platelet aggregation induced by 20 microM ADP was reduced to