Albassam Ahmed A, Markowitz John S
Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Kingdom of Saudi Arabia.
Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, Florida, USA.
Planta Med. 2017 Apr;83(6):496-508. doi: 10.1055/s-0043-100934. Epub 2017 Jan 24.
This review summarizes published , animal, and clinical studies investigating the effects of green tea () extract and associated catechins on drug-metabolizing enzymes and drug transporters. studies suggest that green tea extract and its main catechin, (-)-epigallocatechin-3-gallate, to varying degrees, inhibit the activity of CYP1A1, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2D6, and CYP3A4. UGT1A1 and UGT1A4 isoforms were also inhibited by (-)-epigallocatechin-3-gallate. Animal studies suggest green tea extract and/or (-)-epigallocatechin-3-gallate significantly increase the bioavailability of diltazem, verapamil, tamoxifen simvastatin, 5-fluorouracil, and nicardipine. Conversely, green tea extract and/or (-)-epigallocatechin-3-gallate reduce the bioavailability of quetiapine, sunitinib, clozapine, and nadolol. Of the few clinical studies available for review, it appears neither green tea extract nor (-)-epigallocatechin-3-gallate inhibit any major cytochrome P450 enzyme. Regarding drug transporters, studies indicate P-glycoprotein, organic anion transporting polypeptide 1A1, organic anion transporting polypeptide 1B1, organic anion transporting polypeptide 1B3, organic anion transporting polypeptide 2B1, organic cation transporter 1, organic cation transporter 2, multidrug and toxin extrusion 1, and multidrug and toxin extrusion 2-K are potentially inhibited by green tea extract. A clinical study indicates the organic anion transporting polypeptide 1A1 transporter is inhibited by (-)-epigallocatechin-3-gallate while P-glycoprotein is unaffected. In conclusion, the ingestion of green tea extract or its associated catechins is not expected to result in clinically significant influences on major cytochrome P450 or uridine 5'-diphospho-glucuronosyltransferase enzyme substrates or drugs serving as substrates of P-glycoprotein. However, some caution is advised in the consumption of significant amounts of green tea beverages or green tea extract in patients prescribed known substrates of organic anion transporting polypeptide, particularly those with a narrow therapeutic index.
本综述总结了已发表的、动物和临床研究，这些研究调查了绿茶提取物及其相关儿茶素对药物代谢酶和药物转运体的影响。研究表明，绿茶提取物及其主要儿茶素（-）-表没食子儿茶素-3-没食子酸酯在不同程度上抑制CYP1A1、CYP1A2、CYP2B6、CYP2C8、CYP2C9、CYP2D6和CYP3A4的活性。（-）-表没食子儿茶素-3-没食子酸酯也抑制UGT1A1和UGT1A4同工型。动物研究表明，绿茶提取物和/或（-）-表没食子儿茶素-3-没食子酸酯可显著提高地尔硫卓、维拉帕米、他莫昔芬、辛伐他汀、5-氟尿嘧啶和尼卡地平的生物利用度。相反，绿茶提取物和/或（-）-表没食子儿茶素-3-没食子酸酯会降低喹硫平、舒尼替尼、氯氮平和纳多洛尔的生物利用度。在可供综述的少数临床研究中，似乎绿茶提取物和（-）-表没食子儿茶素-3-没食子酸酯均未抑制任何主要的细胞色素P450酶。关于药物转运体，研究表明绿茶提取物可能抑制P-糖蛋白、有机阴离子转运多肽1A1、有机阴离子转运多肽1B1、有机阴离子转运多肽1B3、有机阴离子转运多肽2B1、有机阳离子转运体1、有机阳离子转运体2、多药和毒素外排转运体1以及多药和毒素外排转运体2-K。一项临床研究表明，（-）-表没食子儿茶素-3-没食子酸酯可抑制有机阴离子转运多肽1A1转运体，而P-糖蛋白不受影响。总之，摄入绿茶提取物或其相关儿茶素预计不会对主要的细胞色素P450或尿苷5'-二磷酸葡萄糖醛酸基转移酶底物或作为P-糖蛋白底物的药物产生临床上显著的影响。然而，对于服用已知有机阴离子转运多肽底物的患者，尤其是那些治疗指数较窄的患者，建议谨慎饮用大量绿茶饮料或绿茶提取物。
