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

文献类型： 外文期刊

第一作者： Zhai, Qianqian

作者： Zhai, Qianqian;Xu, Yang;Li, Cuiping;Feng, Yanyan;Cui, Yanting;Ma, Li;Li, Jian;Zhai, Qianqian;Xu, Yang;Li, Cuiping;Feng, Yanyan;Cui, Yanting;Ma, Li;Li, Jian

作者机构：

关键词： BCRP; Exopalaemon carinicauda; pharmacokinetics; enrofloxacin; Ko143

期刊名称：JOURNAL OF OCEAN UNIVERSITY OF CHINA （ 影响因子：0.913； 五年影响因子：1.012 ）

ISSN： 1672-5182

年卷期： 2020 年 19 卷 5 期

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收录情况： SCI

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.BCRPgene highly expressed in the hepatopancreas and intestine ofExopalaemon carinicaudaas was determined with real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) method. The effects of Ko143 on the abundance ofBCRPmRNA and ENRO pharmacokinetics inE. carinicaudawere studied. The mRNA abundance ofBCRPdecreased 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(1/2 alpha)), elimination half-life (t(1/2 beta)), 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 downregulatesBCRPexpression in hepatopancreas and intestine, thus affects the pharmacokinetics of orally administered enrofloxacin inE. 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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