Research Division, Federal Institute of Drugs and Medical Devices (BfArM), Bonn, Germany.
Institute of Pharmacology of Natural Products and Clinical Pharmacology, University of Ulm, Ulm, Germany.
PLoS One. 2018 Feb 21;13(2):e0193074. doi: 10.1371/journal.pone.0193074. eCollection 2018.
Green tea polyphenols may contribute to the prevention of cancer and other diseases. To learn more about the pharmacokinetics and interindividual variation of green tea polyphenols after oral intake in humans we performed a population nutrikinetic study of standardized green tea extract. 84 healthy participants took green tea extract capsules standardized to 150 mg epigallocatechin-gallate (EGCG) twice a day for 5 days. On day 5 catechin plasma concentrations were analyzed using non-compartmental and population pharmacokinetic methods. A strong between-subject variability in catechin pharmacokinetics was found with maximum plasma concentrations varying more than 6-fold. The AUCs of EGCG, EGC and ECG were 877.9 (360.8-1576.5), 35.1 (8.0-87.4), and 183.6 (55.5-364.6) h*μg/L respectively, and the elimination half lives were 2.6 (1.8-3.8), 3.9 (0.9-10.7) and 1.8 (0.8-2.9) h, respectively. Genetic polymorphisms in genes of the drug transporters MRP2 and OATP1B1 could at least partly explain the high variability in pharmacokinetic parameters. The observed variability in catechin plasma levels might contribute to interindividual variation in benefical and adverse effects of green tea polyphenols. Our data could help to gain a better understanding of the causes of variability of green tea effects and to improve the design of studies on the effects of green tea polyphenols in different health conditions.
ClinicalTrials.gov: NCT01360320.
未加标签:绿茶多酚可能有助于预防癌症和其他疾病。为了更多地了解人类口服标准化绿茶提取物后绿茶多酚的药代动力学和个体间差异,我们进行了标准化绿茶提取物的人群营养药代动力学研究。84 名健康参与者每天两次服用标准化绿茶提取物胶囊,每次 150 毫克表没食子儿茶素没食子酸酯(EGCG),连续服用 5 天。在第 5 天,使用非房室和群体药代动力学方法分析儿茶素的血浆浓度。发现儿茶素药代动力学个体间存在很强的变异性,最大血浆浓度差异超过 6 倍。EGCG、EGC 和 ECG 的 AUC 分别为 877.9(360.8-1576.5)、35.1(8.0-87.4)和 183.6(55.5-364.6)h*μg/L,消除半衰期分别为 2.6(1.8-3.8)、3.9(0.9-10.7)和 1.8(0.8-2.9)h。药物转运蛋白 MRP2 和 OATP1B1 基因的遗传多态性至少可以部分解释药代动力学参数的高变异性。儿茶素血浆水平的观察到的变异性可能导致绿茶多酚有益和不良反应的个体间差异。我们的数据可以帮助更好地了解绿茶效应变异性的原因,并改善不同健康状况下绿茶多酚效应的研究设计。
临床试验注册:ClinicalTrials.gov:NCT01360320。