Carboxylesterase 1-mediated drug-drug interactions between clopidogrel and simvastatin

Biological & Pharmaceutical Bulletin
Xinwen WangJohn S Markowitz

Abstract

Patients with coronary artery disease often receive concurrent treatment with clopidogrel and a hydroxymethylglutaryl (HMG)-CoA reductase inhibitor medication. Accordingly, potential drug-drug interactions associated with the concomitant use of these agents present an area of concern. Both CYP enzymes and carboxylesterase 1 (CES1) are involved in the metabolism of clopidogrel, while CES1 is believed to be the enzyme responsible for the activation of simvastatin. Some in vitro studies have suggested that simvastatin could attenuate clopidogrel activation via inhibiting CYP3A activity. However, these findings have not found support in several recently published clinical investigations. The present study addresses these inconsistencies by exploring the potential role of CES1 in the metabolism of clopidogrel and simvastatin. Our in vitro human liver s9 fraction incubation study demonstrated that simvastatin significantly enhanced the formation of the intermediate metabolite 2-oxo-clopidogrel, and inhibited the CES1-mediated hydrolysis of clopidogrel, 2-oxo-clopidogrel, and the active metabolite. However, the production of the active metabolite remained unchanged. Conversely, clopidogrel was not found to influence the CES1 mediated ...Continue Reading

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Citations

Apr 8, 2016·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Wei YangXijing Chen
Apr 17, 2016·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Matthew A Cerny
Dec 7, 2017·Frontiers in Pharmacology·Jinfang JiangDafang Zhong
May 24, 2017·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Jinfang JiangDafang Zhong
May 1, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ying LiZhan-Jun Dong
Nov 14, 2020·Phytotherapy Research : PTR·Lei FengXiao-Chi Ma
Jun 27, 2021·Chemico-biological Interactions·Yun-Qing SongGuang-Bo Ge
May 29, 2021·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Anne M FilppulaMikko Niemi

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