Comprehensive Investigation of the Influence of High-Altitude Hypoxia on Clopidogrel Metabolism and Gut Microbiota.

IF 2.1 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Current drug metabolism Pub Date : 2023-01-01 DOI:10.2174/0113892002272030231005103840

Juanhong Zhang, Yuemei Sun, Jiaxin He, Guofan Wu, Rong Wang, Junmin Zhang

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Abstract

Background: The amount of metabolites converted into active metabolites is correspondingly reduced since only more than 50% of clopidogrel is absorbed.

Objective: Exploring the effect of gut microbiota altered by altitude hypoxia on the pre-absorption metabolism of clopidogrel.

Methods: In vitro and in vivo experiments were conducted to analyze the metabolism of clopidogrel through LCMS/ MS, while 16S rRNA analysis was used to investigate the changes in the gut microbiota of high-altitude animals.

Results: We demonstrated that the intestinal flora is involved in the metabolism of clopidogrel through in vivo and in vitro experiments. In addition, the plateau environment caused changes in the number and composition of intestinal microbes. Intriguingly, alterations in the microbial population could lead to an increase in the pre-absorption metabolism of clopidogrel after rapid entry into the plateau, the amount of absorbed blood is thus reduced, which may affect the bioavailability and therapeutic effect of clopidogrel.

Conclusion: Our results not only as a first clinical reference for dose adjustment of clopidogrel in high-altitude environments but also would be helpful to provide a statement on the broader significance within the field of pharmacokinetics or personalized medicine.

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高原缺氧对氯吡格雷代谢及肠道微生物群影响的综合研究。

背景：转化为活性代谢产物的代谢产物量相应减少，因为只有50%以上的氯吡格雷被吸收。目的：探讨高原缺氧改变肠道微生物群对氯吡格雷吸收前代谢的影响。方法：通过LCMS/MS进行体外和体内实验分析氯吡格雷的代谢，同时使用16S rRNA分析研究高海拔动物肠道微生物群的变化。结果：我们通过体内外实验证明，肠道菌群参与了氯吡格雷的代谢。此外，高原环境导致肠道微生物的数量和组成发生变化。有趣的是，微生物种群的改变可能导致氯吡格雷快速进入平台后吸收前代谢的增加，从而减少吸收的血液量，这可能会影响氯吡格雷的生物利用度和治疗效果。结论：我们的研究结果不仅是氯吡格雷在高海拔环境中剂量调整的第一个临床参考，而且有助于阐明其在药代动力学或个性化医学领域的更广泛意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current drug metabolism 医学-生化与分子生物学

CiteScore

4.30

自引率

4.30%

发文量

审稿时长

4-8 weeks

期刊介绍： Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism, pharmacokinetics, and drug disposition. The journal serves as an international forum for the publication of full-length/mini review, research articles and guest edited issues in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the most important developments. The journal covers the following general topic areas: pharmaceutics, pharmacokinetics, toxicology, and most importantly drug metabolism. More specifically, in vitro and in vivo drug metabolism of phase I and phase II enzymes or metabolic pathways; drug-drug interactions and enzyme kinetics; pharmacokinetics, pharmacokinetic-pharmacodynamic modeling, and toxicokinetics; interspecies differences in metabolism or pharmacokinetics, species scaling and extrapolations; drug transporters; target organ toxicity and interindividual variability in drug exposure-response; extrahepatic metabolism; bioactivation, reactive metabolites, and developments for the identification of drug metabolites. Preclinical and clinical reviews describing the drug metabolism and pharmacokinetics of marketed drugs or drug classes.