Inhibition of Breast Cancer Resistance Protein(BCRP) by Ko143 Can Affect Pharmacokinetics of Enrofloxacin in Exopalaemon carinicauda  

作　　者：ZHAI Qianqian XU Yang LI Cuiping FENG Yanyan CUI Yanting MA Li LI Jian 

机构地区：[1]Key Laboratory of Sustainable Development of Marine Fisheries,Ministry of Agriculture and Rural Affairs,Yellow Sea Fisheries Research Institute,Chinese Academy of Fishery Sciences,Qingdao 266071,China [2]Function Laboratory for Marine Fisheries Science and Food Production Processes,Qingdao National Laboratory for Marine Science and Technology,Qingdao 266237,China

出　　处：《Journal of Ocean University of China》2020年第5期1116-1124,共9页中国海洋大学学报（英文版）

基　　金：supported by the Natural Science Foundation of Shandong Province,P. R. China (No. ZR2019QC015);the National Key R&D Program of China (No. 2019YFD0900403);the Central Public-Interest Scientific Institution Basal Research Fund,CAFS (Nos. 2019ZD09 03 and 2020TD46);the Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology (Qingdao)(No. 2018SDKJ0502-2);the Earmarked Fund for Modern Agro-industry Technology Research System (No. CARS-48);the National Natural Science Foundation of China (No. 31873039)。

摘　　要：Adenosine triphosphate-binding cassette transporter breast cancer resistance protein(BCRP) exists highly in the apical membranes of epithelia, and is involved in drug availability. Ko143 is a typical inhibitor of BCRP in rodents. The synthetic antibacterial agent enrofloxacin(ENRO) is a fluoroquinolone employed as veterinary and aquatic medicine, and also a substrate for BCRP. BCRP gene highly expressed in the hepatopancreas and intestine of Exopalaemon carinicauda as was determined with real-time quantitative reverse transcription-polymerase chain reaction(RT-q PCR) method. The effects of Ko143 on the abundance of BCRP m RNA and ENRO pharmacokinetics in E. carinicauda were studied. The m RNA abundance of BCRP decreased significantly in hepatopancreas and intestine(P < 0.05) after Ko143 treatment. Co-administration of Ko143 significantly changed the pharmacokinetics of orally administered enrofloxacin, which was supported by higher distribution half-life(t_(1/2α)), elimination half-life(t_(1/2β)), area under the curve up to the last measurable concentration(AUC_(0-t)), peak concentration(C_(max)) and lower clearance(CL/F). These findings revealed that Ko143 downregulates BCRP expression in hepatopancreas and intestine, thus affects the pharmacokinetics of orally administered enrofloxacin in E. carinicauda. The drug-drug interaction can be caused by the change in BCRP activity if ENRO is used in combination with other drugs in shrimp.

关 键 词：BCRP Exopalaemon carinicauda PHARMACOKINETICS ENROFLOXACIN Ko143 

分 类 号：R969.1[医药卫生—药理学]