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

被引：0
作者：
Qianqian Zhai
Yang Xu
Cuiping Li
Yanyan Feng
Yanting Cui
Li Ma
Jian Li
机构：
[1] Chinese Academy of Fishery Sciences,Key Laboratory of Sustainable Development of Marine Fisheries, Ministry of Agriculture and Rural Affairs, Yellow Sea Fisheries Research Institute
[2] Qingdao National Laboratory for Marine Science and Technology,Function Laboratory for Marine Fisheries Science and Food Production Processes
来源：
Journal of Ocean University of China | 2020年 / 19卷
关键词：
BCRP; pharmacokinetics; enrofloxacin; Ko143;
D O I：
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中图分类号：
学科分类号：
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-qPCR) method. The effects of Ko143 on the abundance of BCRP mRNA and ENRO pharmacokinetics in E. carinicauda were studied. The mRNA 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 (t1/2α), elimination half-life (t1/2β), area under the curve up to the last measurable concentration (AUC0-t), peak concentration (Cmax) 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.
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页码：1116 / 1124
页数：8
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