Intestinal permeability of metformin using single-pass intestinal perfusion in rats

作     者：Nai-Ning Song Quan-Sheng Li Chang-Xiao Liu 

作者机构：School of Chemical Engineering and Technology Tianjin University Tianjin 300072 China National Key Laboratory of Pharmacokinetics and Pharmacodynamics Tianjin Institute of Pharmaceutical Research Tianjin 300193 China National Key Laboratory of Pharmacokinetics and Pharmacodynamics Tianjin Institute of Pharmaceutical Research Tianjin 300193 China 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2006年第12卷第25期

页      面：4064-4070页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：Supported by the National "863" Program of China  No.2003AA2Z347Dthe National "973" Program of China  No.2004CB518902 

主　　题：Metformin Intestinal permeability Single-pass intestinal perfusion P-glycoprotein RP-HPLC 

摘      要：AIM： To characterize the intestinal transport and mechanism of metformin in rats and to investigate whether or not metformin is a substrate for P-glycoprotein （P-gp）. METHODS： The effective intestinal permeability of metformin was investigated using single-pass intestinal perfusion （SPIP） technique in male Waster rats. SPIP was performed in three isolated intestinal segments （duodenum, jejunum and ileum） at the same concentration of metformin （50 μg/mL） to test if the intestinal transport of metformin exhibited site- dependent changes, and in a same isolated intestinal segment （duodenal segment） at three different concentrations of metformin （10, 50, 200 μg/mL） to test if the intestinal transport of metformin exhibited concentration-dependent changes. Besides, P-gp inhibitor verapamil （400 μg/mL） was co-perfused with metformin （50 μg/mL） in the duodenum segment to find out if the intestinal absorption of metformin was affected by P-gp exiting along the gastrointestinal track. Stability studies were conducted to ensure that the loss of metformin could be attributed to intestinal absorption. RESULTS： The effective permeability values （Peff） of metformin in the jejunum and ileum at 50μg/mL were significantly lower than those in the duodenum at the same concentration. Besides, Peff values in the duodenum at high concentration （200 μg/mL） were found to be significantly lower than those at low and medium concentrations （10 and 50 μg/mL）. Moreover the coperfusion with verapamil did not increase the Peff value of metformin at 50 μg/mL in the duodenum. CONCLUSION： Metformin could be absorbed from the whole intestine, with the main absorption site at duodenum. This concentration-dependent permeability behavior in the duodenum indicates that metformin is transported by both passive and active carrier-mediated saturable mechanism. The Peff value can not be increased by co-perfusion with verapamil, indicating that absorption of metformin is not efficiently transported by P-