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

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.