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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 (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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Acknowledgements

This work was supported by the Natural Science Foundation of Shandong Province, P. R. China (No. ZR2019 QC015), 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), and the National Natural Science Foundation of China (No. 31873039).

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Zhai, Q., Xu, Y., Li, C. et al. Inhibition of Breast Cancer Resistance Protein (BCRP) by Ko143 Can Affect Pharmacokinetics of Enrofloxacin in Exopalaemon carinicauda. J. Ocean Univ. China 19, 1116–1124 (2020). https://doi.org/10.1007/s11802-020-4312-9

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  • DOI: https://doi.org/10.1007/s11802-020-4312-9

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