2. Academic Validation
  3. Relevance of Breast Cancer Resistance Protein to Pharmacokinetics of Florfenicol in Chickens: A Perspective from In Vivo and In Vitro Studies

Relevance of Breast Cancer Resistance Protein to Pharmacokinetics of Florfenicol in Chickens: A Perspective from In Vivo and In Vitro Studies

  • Int J Mol Sci. 2018 Oct 15;19(10):3165. doi: 10.3390/ijms19103165.
Yang Liu 1,  Li Guo 2,  Mire Zloh 3,  Yujuan Zhang 4,  Jinhu Huang 5,  Liping Wang 6
Affiliations

Affiliations

  • 1 Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, No. 1 Weigang, Nanjing 210095, China. 2016107021@njau.edu.cn.
  • 2 Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, No. 1 Weigang, Nanjing 210095, China. 2014107023@njau.edu.cn.
  • 3 Faculty of Pharmacy, University Business Academy, Trg Mladenaca 5, 21000 Novi Sad, Serbia. zloh@live.co.uk.
  • 4 Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, No. 1 Weigang, Nanjing 210095, China. 2016807009@njau.edu.cn.
  • 5 Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, No. 1 Weigang, Nanjing 210095, China. jhuang@njau.edu.cn.
  • 6 Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, No. 1 Weigang, Nanjing 210095, China. wlp71@njau.edu.cn.
PMID: 30326566 DOI: 10.3390/ijms19103165
Abstract

Florfenicol (FFC) is a valuable synthetic fluorinated derivative of thiamphenicol widely used to treat infectious diseases in food Animals. The aims of the study were to investigate whether FFC is a substrate for the breast Cancer resistance protein (BCRP) and whether the transporter influences oral availability of FFC. In vitro transport assays using MDCK-chAbcg2 cells were conducted to assess chicken BCRP-mediated transport of FFC, while in vivo pharmacokinetic experiments with single or combined BCRP Inhibitor gefitinib were employed to study the role of BCRP in oral FFC disposition. According to U.S. Food and Drug Administration (FDA) criteria, FFC was found to be a potential BCRP substrate due to the net efflux ratio being over 2.0 (2.37) in MDCK cells stably transfected with chicken BCRP and the efflux completely reversed by a BCRP Inhibitor (Gefitinib). The molecular docking results indicated that florfenicol can form favorable interactions with the binding pocket of homology modeled chicken BCRP. Pharmacokinetic studies of FFC in different aged broilers with different expression levels of BCRP showed that higher BCRP expression would cause a lower Area Under Curve (AUC) and a higher clearance of FFC. In addition, more extensive absorption of florfenicol after the co-administration with gefitinib (a BCRP Inhibitor) was observed. The overall results demonstrated that florfenicol is a substrate of the chicken breast Cancer resistant protein which in turn affects its pharmacokinetic behavior.

Keywords

chicken breast cancer resistant protein; florfenicol; substrate.

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