Semin Thromb Hemost 2005; 31(2): 184-194
DOI: 10.1055/s-2005-869524
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.

Pharmacology of CS-747 (prasugrel, LY640315), a Novel, Potent Antiplatelet Agent with in Vivo P2Y12 Receptor Antagonist Activity

Yoichi Niitsu1 , Joseph A. Jakubowski3 , Atsuhiro Sugidachi1 , Fumitoshi Asai1 , 2
  • 1Pharmacology and Molecular Biology Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan
  • 2Director, BioTechnology Discovery Research, Eli Lilly and Company, Indianapolis, Indiana
  • 3BioTechnology Discovery Research, Eli Lilly and Company, Indianapolis, Indiana
Further Information

Publication History

Publication Date:
26 April 2005 (online)

ABSTRACT

CS-747 (prasugrel, LY640315) is a member of the thienopyridine class of oral platelet aggregation inhibitors that includes ticlopidine and clopidogrel. A single oral administration of CS-747 produced a dose-related inhibition of platelet aggregation in rats that was approximately 10- and 100-fold more potent than that of clopidogrel and ticlopidine, respectively. The antiaggregatory effect of CS-747 was evident at 30 minutes and lasted until 72 hours after dosing, indicating fast onset and long duration of action. CS-747 showed more potent antithrombotic activity compared with clopidogrel and ticlopidine with the same rank order as the antiaggregatory potencies. Combined administration of CS-747 with aspirin to rats produced substantially greater inhibition of both platelet aggregation and thrombus formation compared with each agent alone. The antiplatelet action of CS-747 is due to irreversible and selective blockade of platelet P2Y12 adenosine diphosphate (ADP) receptors by its active metabolite R-138727. In phase I studies, a single oral dose of CS-747 (30 and 75 mg) produced > 50% inhibition of ADP-induced platelet aggregation, with rapid onset (1 hour) and long duration (> 48 hours) of action. In healthy volunteers, once-daily administration of 10 mg CS-747 for 10 days showed significant cumulative inhibition of platelet aggregation from 2 days after the first dose until at least 2 days after the final dose. Studies conducted to date indicate that CS-747 is a highly effective antiplatelet and antithrombotic agent and is anticipated to be effective in the treatment of atherothrombotic and other ischemic vascular diseases.

REFERENCES

Fumitoshi Asai, Ph.D. 

Pharmacology and Molecular Biology Research Laboratories, Sankyo Co., Ltd.

1-2-58 Hiromachi, Shinagawa-ku

Tokyo 140-8710, Japan

Email: toasai@sankyo.co.jp