Department of Pharmacology, School of Medicine, Fukushima Medical University, Fukushima, Japan.
Phytomedicine. 2013 Nov 15;20(14):1247-50. doi: 10.1016/j.phymed.2013.07.003. Epub 2013 Aug 3.
Green tea catechins have been shown to affect the activities of drug transporters in vitro, including P-glycoprotein and organic anion transporting polypeptides. However, it remains unclear whether catechins influence the in vivo disposition of substrate drugs for these transporters. In the present study, we investigated effects of green tea extract (GTE) and (-)-epigallocatechin-3-gallate (EGCG) on pharmacokinetics of a non-selective hydrophilic β-blocker nadolol, which is reported to be a substrate for several drug transporters and is not metabolized by cytochrome P450 enzymes. Male Sprague-Dawley rats received GTE (400 mg/kg), EGCG (150 mg/kg) or saline (control) by oral gavage, 30 min before a single intragastric administration of 10 mg/kg nadolol. Plasma and urinary concentrations of nadolol were determined using high performance liquid chromatography. Pharmacokinetic parameters were estimated by a noncompartmental analysis. Pretreatment with GTE resulted in marked reductions in the maximum concentration (Cmax) and area under the time-plasma concentration curve (AUC) of nadolol by 85% and 74%, respectively, as compared with control. In addition, EGCG alone significantly reduced Cmax and AUC of nadolol. Amounts of nadolol excreted into the urine were decreased by pretreatments with GTE and EGCG, while the terminal half-life of nadolol was not different among groups. These results suggest that the coadministration with green tea catechins, particularly EGCG, causes a significant alteration in the pharmacokinetics of nadolol, possibly through the inhibition of its intestinal absorption mediated by uptake transporters.
绿茶儿茶素已被证明能影响药物转运体的体外活性，包括 P-糖蛋白和有机阴离子转运多肽。然而，儿茶素是否影响这些转运体的底物药物的体内处置仍不清楚。在本研究中，我们研究了绿茶提取物（GTE）和（-）-表没食子儿茶素-3-没食子酸酯（EGCG）对非选择性亲水性β受体阻滞剂纳多洛尔药代动力学的影响，据报道，纳多洛尔是几种药物转运体的底物，且不被细胞色素 P450 酶代谢。雄性 Sprague-Dawley 大鼠在单次灌胃给予 10mg/kg 纳多洛尔前 30 分钟，经口给予 GTE（400mg/kg）、EGCG（150mg/kg）或生理盐水（对照）。采用高效液相色谱法测定血浆和尿中纳多洛尔的浓度。采用非房室分析估算药代动力学参数。与对照组相比，GTE 预处理使纳多洛尔的最大浓度（Cmax）和时间-血浆浓度曲线下面积（AUC）分别显著降低 85%和 74%。此外，EGCG 单独处理也显著降低了纳多洛尔的 Cmax 和 AUC。GTE 和 EGCG 预处理使纳多洛尔的尿排泄量减少，而纳多洛尔的终末半衰期在各组间无差异。这些结果表明，与绿茶儿茶素（特别是 EGCG）联合使用会导致纳多洛尔的药代动力学发生显著改变，可能是通过抑制其肠道吸收介导的摄取转运体。
