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Relevance of Breast Cancer Resistance Protein to Pharmacokinetics of Florfenicol in Chickens: A Perspective from In Vivo and In Vitro Studies
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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214120/ https://www.ncbi.nlm.nih.gov/pubmed/30326566 http://dx.doi.org/10.3390/ijms19103165 |
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author | Liu, Yang Guo, Li Zloh, Mire Zhang, Yujuan Huang, Jinhu Wang, Liping |
author_facet | Liu, Yang Guo, Li Zloh, Mire Zhang, Yujuan Huang, Jinhu Wang, Liping |
author_sort | Liu, Yang |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6214120 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62141202018-11-14 Relevance of Breast Cancer Resistance Protein to Pharmacokinetics of Florfenicol in Chickens: A Perspective from In Vivo and In Vitro Studies Liu, Yang Guo, Li Zloh, Mire Zhang, Yujuan Huang, Jinhu Wang, Liping Int J Mol Sci Article 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. MDPI 2018-10-15 /pmc/articles/PMC6214120/ /pubmed/30326566 http://dx.doi.org/10.3390/ijms19103165 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Liu, Yang Guo, Li Zloh, Mire Zhang, Yujuan Huang, Jinhu Wang, Liping Relevance of Breast Cancer Resistance Protein to Pharmacokinetics of Florfenicol in Chickens: A Perspective from In Vivo and In Vitro Studies |
title | Relevance of Breast Cancer Resistance Protein to Pharmacokinetics of Florfenicol in Chickens: A Perspective from In Vivo and In Vitro Studies |
title_full | Relevance of Breast Cancer Resistance Protein to Pharmacokinetics of Florfenicol in Chickens: A Perspective from In Vivo and In Vitro Studies |
title_fullStr | Relevance of Breast Cancer Resistance Protein to Pharmacokinetics of Florfenicol in Chickens: A Perspective from In Vivo and In Vitro Studies |
title_full_unstemmed | Relevance of Breast Cancer Resistance Protein to Pharmacokinetics of Florfenicol in Chickens: A Perspective from In Vivo and In Vitro Studies |
title_short | Relevance of Breast Cancer Resistance Protein to Pharmacokinetics of Florfenicol in Chickens: A Perspective from In Vivo and In Vitro Studies |
title_sort | relevance of breast cancer resistance protein to pharmacokinetics of florfenicol in chickens: a perspective from in vivo and in vitro studies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214120/ https://www.ncbi.nlm.nih.gov/pubmed/30326566 http://dx.doi.org/10.3390/ijms19103165 |
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