药物转运体在反式白藜芦醇肠道吸收中的作用  

Effects of drug transporters on the intestinal absorption of trans-resveratrol

作　　者：何卉[1] 陈西敬[1] 王广基[1] 

机构地区：[1]中国药科大学药物代谢动力学重点实验室,南京210009

出　　处：《中国药科大学学报》2008年第4期324-328,共5页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.30472060);国家高技术研究发展计划("八六三"计划)资助项目(No.2003AA2Z347A);江苏省药物代谢动力学重点实验室资助项目(No.2001201)~~

摘　　要：目的:通过体内和体外模型研究多药耐药相关蛋白(Mrp-2)外排底物溴磺肽钠对反式白藜芦醇(trans-resvera-trol,TR)肠道吸收的影响,并对转运体在TR肠道吸收中的作用进行研究。方法:应用离体肠外翻模型,测定不同时间点时肠囊内TR的浓度,寻找TR在肠中吸收的最佳部位;观察多种P-糖蛋白及Mrp-2抑制剂对TR吸收的影响;根据离体肠外翻吸收试验结果,选择溴磺肽钠作为促吸收剂,研究不同给药途径的溴磺肽钠对TR在大鼠体内药动学行为的影响。结果:TR在不同肠段均具有很高的通透性(Papp>1×10-6cm/s),回肠是TR的最佳吸收部位。Mrp-2外排抑制剂丙璜舒及底物溴磺肽钠都能够显著增加TR在回肠部位的吸收;P-糖蛋白及Mrp-2共同底物甲氨碟呤也能够增加TR的肠吸收;而P-糖蛋白抑制剂地高辛和维拉帕米无此作用。整体动物实验结果,发现预先给大鼠灌胃溴磺肽钠,可以显著提高TR的口服吸收,TR的生物利用度提高4倍;而溴磺肽钠通过尾静脉注射给药无此作用。结论:Mrp-2参与TR的肠道外排过程,P-糖蛋白对其外排无影响。溴磺肽钠通过灌胃给药途径可增加TR的吸收及生物利用度。Aim： To conduct in vivo and in vitro investigations of the effects of bromosulfophthalein （BSP） on trans-resveratrol （TR） absorption, and to study the possible role of drug transporters in TR intestinal absorption. Methods： TR intestinal absorption and absorption regions were studied by using everted gut sacs, and the influ- ence of Mrp-2 and P-glycoprotein （P-gp） inhibitors on TP absorption was evaluated in everted gut sac. In addi- tion, the effect of BSP on TR pharmacokinetics in intact rats by oral administration and tail vein injection was studied. Results： Application of the everted gut sac showed that TR was well absorbed from the intestinal seg- ments tested （Papp 〉 1 × 10^-6 cm/s）, and it seemed that TR has marked permeability coefficient in rat ileum. Both Mrp-2 inhibitors such as probenecid and nonP-gp inhibitors such as BSP significantly increased TR absorp- tion in the ileum. But no effect was observed in the presence of digoxin and verapamil. In comparison to tail vein injection, oral coadministration of TR with BSP resulted in significant increases in cmax and bioavailability. Conclusion： It is proved that Mrp-2 is involved in the TR absorption and that inhibition of Mrp-2 can significantly increase TR absorption and bioavailability in the model via oral route.

关 键 词：反式白藜芦醇 药物转运体 溴磺肽钠 生物利用度 翻转肠囊 

分 类 号：R285[医药卫生—中药学]