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Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Potent and Orally Bioavailable Antiplatelet Agent, PLD-301, with the Potential of Overcoming Clopidogrel Resistance

Author(s): Jingyu Chen and Michael Zhiyan Wang

Volume 13 , Issue 3 , 2016

Page: [250 - 254] Pages: 5

DOI: 10.2174/1570180812666150730221941

open access plus

Abstract

PLD-301, a phosphate prodrug of clopidogrel thiolactone discovered by Prelude Pharmaceuticals with the aim to overcome clopidogrel resistance, was evaluated for its in vivo inhibitory effect on ADP-induced platelet aggregation in rats. The potency of PLD-301 was similar to that of prasugrel, but much higher than that of clopidogrel. The results of pharmacokinetic analysis showed that the oral bioavailability of clopidogrel thiolactone converted from PLD-301 was 4- to 5-fold higher than that of the one converted from clopidogrel, suggesting that in comparison with clopidogrel, lower doses of PLD-301 could be used clinically. In summary, PLD-301 presents a potent and orally bioavailable antiplatelet agent that might have some advantages over clopidogrel, such as overcoming clopidogrel resistance for CYP2C19-allele loss-of-function carriers, and lowering dose-related toxicity due to a much lower effective dose.

Keywords: Clopidogrel, active metabolite, drug resistance, platelet ADP receptor, platelet aggregation, thrombosis.

Graphical Abstract

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