Journal
JOURNAL OF OCEAN UNIVERSITY OF CHINA
Volume 19, Issue 5, Pages 1116-1124Publisher
OCEAN UNIV CHINA
DOI: 10.1007/s11802-020-4312-9
Keywords
BCRP; Exopalaemon carinicauda; pharmacokinetics; enrofloxacin; Ko143
Categories
Funding
- Natural Science Foundation of Shandong Province, P. R. China [ZR2019 QC015]
- National Key R&D Program of China [2019YFD0900403]
- Central Public-Interest Scientific Institution Basal Research Fund, CAFS [2019ZD09 03, 2020TD46]
- Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology (Qingdao) [2018SDKJ0502-2]
- Earmarked Fund for Modern Agro-industry Technology Research System [CARS-48]
- National Natural Science Foundation of China [31873039]
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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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