Contribution of presystemic hepatic extraction to the low oral bioavailability of green tea catechins in rats
Contribution of presystemic hepatic extraction to the low oral bioavailability of green tea catechins in rats
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DOI：
10.1124/dmd.30.11.1246
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发表时间：
2002-11-01
影响因子：
3.9
通讯作者：
Chow, HHS
中科院分区：
文献类型：
--
作者：
Cai, Y;Anavy, ND;Chow, HHS
绿色茶和绿色茶儿茶素在啮齿动物癌症模型中显示出具有有效的癌症预防活性。目前，绿色茶消费对人类癌症发展的保护作用的流行病学证据尚不确定。绿色茶儿茶素的口服生物利用度已被证明在动物和可能在人类中较低。本研究旨在确定首过肝脏消除的贡献低口服生物利用度的绿色茶儿茶素。绿色茶儿茶素混合物通过静脉或门静脉输注给予大鼠。给药后采集血样，并使用高效液相色谱法和库仑电极阵列检测系统进行分析。表没食子儿茶素没食子酸酯（EGCG）、表没食子儿茶素（EGC）和表儿茶素（EC）的全身清除率分别为8.9、6.3和9.4 ml/min。EGCG、EGC和EC的稳态分布容积（V-ss）分别为432、220和187 ml。我们发现，高百分比的绿色茶儿茶素逃脱首过肝脏消除，与87.0，108.3，和94.9%的表没食子儿茶素没食子酸酯，和EC，分别可在全身血液门静脉输注后。我们的研究结果表明，胃肠道内的因素，如有限的膜渗透性，转运介导的肠道分泌，或肠壁代谢可能会更显着的低口服生物利用度的绿色茶儿茶素。
Green tea and green tea catechins have been shown to possess potent cancer-preventive activities in rodent cancer models. At present, epidemiological evidence of the protective effect of green tea consumption against the development of human cancers is not conclusive. Oral bioavailability of green tea catechins has been shown to be low in animals and possibly in humans. This study is designed to determine the contribution of first-pass hepatic elimination to the low oral bioavailability of green tea catechins. Green tea catechin mixture was dosed to rats by intravenous or intraportal infusion. Blood samples were collected after dosing and analyzed using high-performance liquid chromatography with the coulometric electrode array detection system. The systemic clearance of epigallocatechin gallate (EGCG), epigallocatechin (EGC), and epicatechin (EC) was 8.9, 6.3, and 9.4 ml/min, respectively. The steady state volume of distribution (V-ss) of EGCG, EGC, and EC was 432, 220, and 187 ml, respectively. We found that high percentage of green tea catechins escaped first-pass hepatic elimination, with 87.0, 108.3, and 94.9% of EGCG, EGC, and EC, respectively, available in the systemic blood following intraportal infusion. Our results suggest that factors within the gastrointestinal tract such as limited membrane permeability, transporter mediated intestinal secretion, or gut wall metabolism may contribute more significantly to the low oral bioavailability of green tea catechins.