Submit Manuscript  

Article Details


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

[ Vol. 13 , Issue. 3 ]

Author(s):

Jingyu Chen and Michael Zhiyan Wang   Pages 250 - 254 ( 5 )

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.

Affiliation:

Prelude Pharmaceuticals, 99 14th KeChuang Street, Building 33, Suite D-601, Beijing Economic- Technological Development Area, Beijing 101111, China.

Graphical Abstract:



Read Full-Text article