Hepatoenteric recycling is a new disposition mechanism for orally administered phenolic drugs and phytochemicals in rats.
Hepatoenteric recycling is a new disposition mechanism for orally administered phenolic drugs and phytochemicals in rats.
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作者：
Tu Y;Wang L;Rong Y;Tam V;Yin T;Gao S;Singh R;Hu M
许多口服的酚类药物经历了肠肝循环(EHR)，推测是由肝脏II相酶介导的。然而，肝外生成的II相代谢物的处置尚不清楚。本文旨在确定肝脏和肠道在口腔酚类物质处置中的新作用。16种具有代表性的酚类化合物采用门静脉直接输注和/或肠道灌流的方法进行了测试。结果表明，某些葡萄糖醛酸类化合物能有效地被肝脏循环利用。OATP1B1/1B3/2B1是主要的摄取转运体。肝脏摄取是肝脏循环的限速步骤。我们的研究结果表明，许多口服酚类物质的处置是通过肠道葡萄糖醛酸化和肝脏循环来调节的。揭示了一种以肠道为代谢器官，肝脏为循环器官的新的代谢机制--肝肠循环。以她为重点的进一步研究应该有助于解释肠道食物或联合使用改变肠道酶(例如UGT)表达/活性的药物将如何影响酚类物质的处置。
Many orally administered phenolic drugs undergo enterohepatic recycling (EHR), presumably mediated by the hepatic phase II enzymes. However, the disposition of extrahepatically generated phase II metabolites is unclear. This paper aims to determine the new roles of liver and intestine in the disposition of oral phenolics. Sixteen representative phenolics were tested using direct portal vein infusion and/or intestinal perfusion. The results showed that certain glucuronides were efficiently recycled by liver. OATP1B1/1B3/2B1 were the responsible uptake transporters. Hepatic uptake is the rate-limiting step in hepatic recycling. Our findings showed that the disposition of many oral phenolics is mediated by intestinal glucuronidation and hepatic recycling. A new disposition mechanism ‘Hepatoenteric Recycling (HER)”, where intestine is the metabolic organ and liver is the recycling organ, was revealed. Further investigations focusing on HER should help interpret how intestinal aliments or co-administered drugs that alter gut enzymes (e.g. UGTs) expression/activities will impact the disposition of phenolics.