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

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          Abstract

          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 ( 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.

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          Author and article information

          Journal
          JOUC
          Journal of Ocean University of China
          Science Press and Springer (China )
          1672-5182
          02 September 2020
          01 October 2020
          : 19
          : 5
          : 1116-1124
          Affiliations
          1Key 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
          2Function Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China
          Author notes
          *Corresponding authors: ZHAI Qianqian, E-mail: zqq0817@ 123456163.com ; LI Jian, E-mail: lijian@ 123456ysfri.ac.cn
          Article
          s11802-020-4312-9
          10.1007/s11802-020-4312-9
          Copyright © Ocean University of China, Science Press and Springer-Verlag GmbH Germany 2020.

          The copyright to this article, including any graphic elements therein (e.g. illustrations, charts, moving images), is hereby assigned for good and valuable consideration to the editorial office of Journal of Ocean University of China, Science Press and Springer effective if and when the article is accepted for publication and to the extent assignable if assignability is restricted for by applicable law or regulations (e.g. for U.S. government or crown employees).

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          Self URI (journal-page): https://www.springer.com/journal/11802

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