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.
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)。
