Real-time platelet P2Y_(12) receptor occupancy as a promising pharmacodynamics biomarker for bridging the gap between PK/PD of clopidogrel therapy  

作　　者：Haipeng Li Yueming Gu Yumeng Zhao Aiyun Xu Dong Sun Jingkai Gu 

机构地区：[1]Research Center for Drug Metabolism,School of Life Science,Jilin University,Changchun 130012,China [2]State Key Laboratory of Supramolecular Structure and Materials,Center for Supramolecular Chemical Biology,College of Chemistry,Jilin University,Changchun 130012,China [3]Beijing Institute of Drug Metabolism,Beijing 102209,China

出　　处：《Acta Pharmaceutica Sinica B》2025年第1期484-493,共10页药学学报(英文版)

基　　金：supported by the Scientific and Technological Development Plan of Jilin Province China(Grant No.20210204068YY).

摘　　要：Clopidogrel effectively inhibits platelet aggregation in response to ADP by irreversibly binding to the platelet P2Y_(12) receptor through its active metabolite.However,the observed discrepancies between the pharmacokinetics(PK)and pharmacodynamics(PD)of clopidogrel present substantial challenges in individualizing of antiplatelet therapy.To address these challenges,a robust liquid chromatographyetandem mass spectrometry method has been developed to facilitate the real-time assessment of platelet P2Y_(12) receptor occupancy.This method has been validated in animal models,providing a reliable link between individual PK profiles and PD effects.Target receptor occupancy offers a comprehensive overview of interindividual variations in clopidogrel metabolism,regulation of P2Y_(12) receptor expression,and platelet turnover.Moreover,it directly correlates with the inhibitory effect on platelet aggregation.The levels of platelet P2Y_(12) occupancy accurately reflect the extent of clinical factors influencing the PD of clopidogrel,including dosage,drugedrug interactions(DDI),and type 2 diabetes mellitus(T2DM).As a normalized metric,platelet P2Y_(12) occupancy not only serves potential as a diagnostic tool for personalized clopidogrel therapy but also aids in elucidating the role of the P2Y_(12) signaling pathway in cases of abnormal on-treatment platelet reactivity.

关 键 词：CLOPIDOGREL P2Y_(12) ANTIPLATELET Real-time receptor occupancy PDbiomarker 

分 类 号：R54[医药卫生—心血管疾病]