The effects of multidrug resistance protein 2 (Mrp2) and breast cancer resistance protein (Bcrp) on biliary excretion of cefditoren in rats

作     者：MENG Qiang,LIU Qi,WANG Chang-yuan,LIU Ke-xin(Dalian Medical University,Dalian 116044,China) 

出 版 物：《沈阳药科大学学报》 (Journal of Shenyang Pharmaceutical University)

年 卷 期：2008年第25卷第S1期

页      面：79-80页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：Mrp2 Bcrp cefditoren 

摘      要：Objective Cefditoren,a third-generation cephalosporin antibiotics,has been used in clinic *** Mrp2 or other canalicular transporters such as Bcrp and P-gp are involved in the biliary excretion of cefditoren is *** study is performed to investigate the role of the canalicular transporters in the biliary excretion of cefditoren and the effect of cefditoren on expression levels of some hepatic *** We examined the hepatobiliary disposition of cefditoren using probenecid,novobiocin and verapamil as the inhibitors of Mrp2,Bcrp and P-gp respectively in perfused rat *** concentration of cefditoren in the perfusate and bile were determined by RP-HPLC with ultraviolet detection at 295nm using a mobile phase composed of 0.1% ammonium acetate-methanol(65∶35).We also investigated the effects of cefditoren on expression of hepatic *** change in mRNA of main canalicular transporters was investigated by RT-PCR and Western blot after administration of *** The values for the hepatic extraction ratio did not change,whereas cumulative biliary excretion rates of cefditoren were significantly reduced to 43.78% and 79.52% over 25 min in the perfused probenecid and novobiocin rats,*** oral administration of cefditoren,the expression levels of Mrp2,Bcrp,Oat2 mRNA were markedly up-regulated,while Mdr1a and Oct1 mRNA were down-regulated by *** concordance with RT-PCR results,Mrp2 expression level was up-regulated by Western *** Mrp2 and Bcrp mediated the biliary excretion of cefditoren,whereas P-gp had no contribution to the transportation of cefditoren into *** expression levels of Mrp2,Bcrp and Oat2 mRNA were up-regulated and the expression levels of Mdr1a and Oct1 mRNA were down-regulated by *** results provide important data for drug-drug interaction.