Chow H H, Cai Y, Alberts D S, Hakim I, Dorr R, Shahi F, Crowell J A, Yang C S, Hara Y
Arizona Cancer Center, The University of Arizona, Tucson 85724, USA.
Cancer Epidemiol Biomarkers Prev. 2001 Jan;10(1):53-8.
Green tea has been shown to exhibit cancer-preventive activities in preclinical studies. Its principal active components include epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin (EC), and epicatechin gallate, of which EGCG is the most abundant and possesses the most potent antioxidative activity. We performed a Phase I pharmacokinetic study to determine the systemic availability of green tea catechins after single oral dose administration of EGCG and Polyphenon E (decaffeinated green tea catechin mixture). Twenty healthy subjects (five subjects/dose level) were randomly assigned to one of the dose levels (200, 400, 600, and 800 mg based on EGCG content). All subjects were randomly crossed-over to receive the two catechin formulations at the same dose level. Blood and urine samples were collected for up to 24 h after oral administration of the study medication. Tea catechin concentrations in plasma and urine samples were determined using high-performance liquid chromatography with the coulometric electrode array detection system. After EGCG versus Polyphenon E administration, the mean area under the plasma concentration-time curves (AUC) of unchanged EGCG were 22.5 versus 21.9, 35.4 versus 52.2, 101.9 versus 79.7, and 167.1 versus 161.4 min x microg/ml at the 200-, 400-, 600-, and 800-mg dose levels, respectively. EGC and EC were not detected in plasma after EGCG administration and were present at low/undetectable levels after Polyphenon E administration. High concentrations of EGC and EC glucuronide/sulfate conjugates were found in plasma and urine samples after Polyphenon E administration. There were no significant differences in the pharmacokinetic characteristics of EGCG between the two study medications. The AUC and maximum plasma concentration (Cmax) of EGCG after the 800-mg dose of EGCG were found to be significantly higher than those after the 200- and 400-mg dose. The AUC and Cmax of EGCG after the 800-mg dose of Polyphenon E were significantly higher than those after the three lower doses. We conclude that the two catechin formulations resulted in similar plasma EGCG levels. EGC and EC were present in the body after the Polyphenon E administration; however, they were present predominantly in conjugated forms. The systemic availability of EGCG increased at higher doses, possibly due to saturable presystemic elimination of orally administered green tea polyphenols.
在临床前研究中，绿茶已显示出具有防癌活性。其主要活性成分包括表没食子儿茶素没食子酸酯（EGCG）、表没食子儿茶素（EGC）、表儿茶素（EC）和表儿茶素没食子酸酯，其中EGCG含量最为丰富，且具有最强的抗氧化活性。我们进行了一项I期药代动力学研究，以确定单次口服EGCG和Polyphenon E（脱咖啡因绿茶儿茶素混合物）后绿茶儿茶素的全身可用性。20名健康受试者（每个剂量水平5名受试者）被随机分配到一个剂量水平（基于EGCG含量分别为200、400、600和800毫克）。所有受试者随机交叉接受相同剂量水平的两种儿茶素制剂。口服研究药物后长达24小时收集血液和尿液样本。使用带电量检测电极阵列系统的高效液相色谱法测定血浆和尿液样本中的儿茶素浓度。给予EGCG与给予Polyphenon E后，在200毫克、400毫克、600毫克和800毫克剂量水平下，未变化的EGCG的血浆浓度-时间曲线下平均面积（AUC）分别为22.5对21.9、35.4对52.2、101.9对79.7以及167.1对161.4分钟×微克/毫升。给予EGCG后血浆中未检测到EGC和EC，给予Polyphenon E后它们以低水平/未检测到的水平存在。给予Polyphenon E后，在血浆和尿液样本中发现了高浓度的EGC和EC葡糖醛酸/硫酸酯共轭物。两种研究药物之间EGCG的药代动力学特征没有显著差异。发现800毫克剂量的EGCG给药后EGCG的AUC和最大血浆浓度（Cmax）显著高于200毫克和400毫克剂量给药后的水平。800毫克剂量的Polyphenon E给药后EGCG的AUC和Cmax显著高于三个较低剂量给药后的水平。我们得出结论，两种儿茶素制剂导致血浆EGCG水平相似。给予Polyphenon E后体内存在EGC和EC；然而，它们主要以共轭形式存在。EGCG的全身可用性在较高剂量时增加，可能是由于口服绿茶多酚的首过消除达到饱和。
