Curcumin affects the pharmacokinetics of florfenicol by downregulating the expression of breast cancer-resistant protein in poultry

Abstract

The administration of drugs via the oral route is challenging due to the presence of physiologic barrier. BCRP, which can actively transport substrates from intra- to extracellular environment, has an important functional role in the composition of physiologic barrier. Therefore, overcoming BCRP efflux is a strategy to improve the absorption of substrate drugs. Curcumin is a natural feed additive for poultry health and production. However, it is unknown whether curcumin affects the expression of BCRP. The purpose of this study was to investigate the role of curcumin in the regulation of BCRP and its influences on pharmacokinetics of BCRP substrate florfenicol. Results showed that curcumin (60 μM) inhibited the expression of BCRP mRNA by 58% and BCRP protein by 52% in primary chicken hepatocytes. Moreover, intracellular mitoxantrone (a selective BCRP substrate) fluorescence was 1.58-fold higher in cells pretreated with 60 μM curcumin than in untreated cells, indicating that curcumin inhibited the transport function of BCRP. In vivo experiments showed that curcumin reduced BCRP expression in the liver, kidney, duodenum, jejunum and ileum of chicken. Coadministration of curcumin (150 mg/kg) significantly changed the pharmacokinetic behavior of orally administered florfenicol (substrate of chicken BCRP), with a higher area under the curve (35.51 vs. 25.81 h·ug/L) and a higher C_max values (9.94 vs. 7.61 μg/mL). The bioavailability of orally administered florfenicol was increased from 51.6 to 72.8% by curcumin. Together, our results indicate that curcumin inhibited the expression and efflux function of BCRP in chicken and improved the bioavailability of BCRP substrate florfenicol.