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绿茶提取物与药物性肝损伤风险

Green tea extract and the risk of drug-induced liver injury.

作者信息

Teschke Rolf, Zhang Li, Melzer Lena, Schulze Johannes, Eickhoff Axel

机构信息

Department of Internal Medicine II, Division of Gastroenterology and Hepatology , Klinikum Hanau , Germany

出版信息

Expert Opin Drug Metab Toxicol. 2014 Dec;10(12):1663-76. doi: 10.1517/17425255.2014.971011. Epub 2014 Oct 15.

Abstract

INTRODUCTION

Catechins of green tea extract (GTE) have been associated with the rare risk of hepatotoxicity in a few individuals. As GTE were coadministered with synthetic drugs in some hepatotoxicity cases, uncertainty emerged whether GTE are a risk factor of drug-induced liver injury (DILI).

AREAS COVERED

Case reports of liver injury by GTE and related review articles to assess the drugs that were coadministered with GTE were reviewed. The analysis included the question whether a formal causality of liver injury had confidently been attributed to GTE, the comedicated drug(s) or both. To elucidate possible metabolic interactions, GTE and their catechins were analyzed regarding their affinity to various CYP isoforms.

EXPERT OPINION

The authors conclude that the published hepatotoxicity case reports in connection with the use of GTE provide no clinical evidence that GTE may increase the risk of DILI by drugs that had been comedicated in only few cases. Although partial inhibition of human hepatic and intestinal microsomal CYP2C8, CYP2B6, CYP3A4, CYP2D6 and CYP2C19 by GTE catechins was observed in vitro, a clinical study of drug bioavailability attributed a small risk of increased plasma drug levels only for substrates metabolized by CYP3A4, lacking clinical relevance.

摘要

引言

绿茶提取物(GTE)中的儿茶素与少数个体发生肝毒性的罕见风险有关。由于在一些肝毒性病例中GTE与合成药物同时给药,因此GTE是否为药物性肝损伤(DILI)的危险因素尚不确定。

涵盖领域

对GTE导致肝损伤的病例报告以及相关综述文章进行了回顾,这些文章评估了与GTE同时给药的药物。分析内容包括肝损伤的正式因果关系是否已明确归因于GTE、同时服用的药物或两者。为了阐明可能的代谢相互作用,对GTE及其儿茶素与各种CYP同工酶的亲和力进行了分析。

专家意见

作者得出结论,已发表的与使用GTE相关的肝毒性病例报告没有提供临床证据表明GTE会增加仅在少数病例中同时服用的药物导致DILI的风险。尽管在体外观察到GTE儿茶素对人肝和肠微粒体CYP2C8、CYP2B6、CYP3A4、CYP2D6和CYP2C19有部分抑制作用,但一项关于药物生物利用度的临床研究表明,仅对于由CYP3A4代谢的底物,血浆药物水平升高的风险很小,缺乏临床相关性。

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