Department of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai, China.
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
J Food Sci. 2020 Apr;85(4):1285-1291. doi: 10.1111/1750-3841.15096. Epub 2020 Mar 10.
Green tea is widely consumed as a beverage and/or dietary supplement worldwide, resulting in the difficulty to avoid the comedication with ticagrelor for acute coronary syndrome (ACS) patients receiving antiplatelet therapy. This study was designed to investigate the effect of the most abundant content in green tea, tea polyphenols on the oral and intravenous pharmacokinetics of ticagrelor in rats and its in vitro metabolism. Rats were orally treated with either saline or tea polyphenol extracts (TPEs) dissolved in saline once daily for 6 consecutive days. On day 6, after the last dose of saline or TPE, ticagrelor was given to the rats orally or intravenously. Plasma samples were collected for pharmacokinetic analysis. Human liver and intestinal microsomes were then used to investigate the inhibition by TPE, as well as its major constituents on the metabolism of ticagrelor to its two metabolites, AR-C124910XX and AR-C133913XX. Apparent kinetic constants and inhibition potency (IC ) for each metabolic pathway of each compound were estimated. Oral study indicated that exposure of ticagrelor and AR-C124910XX was significantly decreased after TPE administration, while no significant differences were observed in pharmacokinetic parameters after intravenous administration of ticagrelor. TPE effectively inhibited the metabolism of ticagrelor in vitro, with epigallocatechin-3-gallate as the major constituent responsible for the observed inhibitory effects in human liver microsomes and intestinal microsomes (IC = 4.23 ± 0.18 µM). Caution should be taken for ACS patients receiving ticagrelor therapy with daily drinking of green tea. PRACTICAL APPLICATION: Potential interactions between tea polyphenols and ticagrelor were revealed for the first time. Results can provide suggestions for clinicians to optimize the dosing of ticagrelor while they are in the face of ACS patients receiving ticagrelor therapy, who also take green tea or its related products in their daily life.
绿茶作为一种饮料和/或膳食补充剂在全球范围内广泛消费，这使得接受抗血小板治疗的急性冠脉综合征（ACS）患者难以避免与替格瑞洛同时用药。本研究旨在研究绿茶中含量最丰富的成分——茶多酚对大鼠口服和静脉给予替格瑞洛的药代动力学的影响及其体外代谢。大鼠连续 6 天每天口服或静脉给予生理盐水或溶于生理盐水的茶多酚提取物（TPE）。第 6 天，在最后一次给予生理盐水或 TPE 后，大鼠给予替格瑞洛口服或静脉给药。采集血浆样品进行药代动力学分析。然后用人肝和肠微粒体研究 TPE 及其主要成分对替格瑞洛代谢为其两种代谢物 AR-C124910XX 和 AR-C133913XX 的抑制作用。估计每个化合物的每个代谢途径的表观动力学常数和抑制效力（IC ）。口服研究表明，TPE 给药后替格瑞洛和 AR-C124910XX 的暴露明显降低，而替格瑞洛静脉给药后药代动力学参数无显著差异。TPE 有效地抑制了替格瑞洛在体外的代谢，表没食子儿茶素-3-没食子酸酯是导致在人肝微粒体和肠微粒体中观察到的抑制作用的主要成分（IC = 4.23 ± 0.18 µM）。接受替格瑞洛治疗的 ACS 患者每天饮用绿茶时应谨慎。实际应用：首次揭示了茶多酚和替格瑞洛之间的潜在相互作用。结果可为临床医生在面对接受替格瑞洛治疗的 ACS 患者时提供建议，同时这些患者在日常生活中也服用绿茶或其相关产品，优化替格瑞洛的剂量。
