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Inhibitory effect of clemastine on P-glycoprotein expression and function: an in vitro and in situ study
OBJECTIVE(S): Transporters have an important role in pharmacokinetics of drugs. Inhibition or induction of drug transporters activity can affect drug absorption, safety, and efficacy. P-glycoprotein (P-gp) is the most important membrane transporter that is responsible for active efflux of drugs. It...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Mashhad University of Medical Sciences
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4887716/ https://www.ncbi.nlm.nih.gov/pubmed/27279987 |
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author | Abbasi, Mehran Mesgari Valizadeh, Hadi Hamishekar, Hamed Mohammadnejad, Leila Zakeri-Milani, Parvin |
author_facet | Abbasi, Mehran Mesgari Valizadeh, Hadi Hamishekar, Hamed Mohammadnejad, Leila Zakeri-Milani, Parvin |
author_sort | Abbasi, Mehran Mesgari |
collection | PubMed |
description | OBJECTIVE(S): Transporters have an important role in pharmacokinetics of drugs. Inhibition or induction of drug transporters activity can affect drug absorption, safety, and efficacy. P-glycoprotein (P-gp) is the most important membrane transporter that is responsible for active efflux of drugs. It is important to understand which drugs are substrates, inhibitors, or inducers of P-gp to minimize or avoid unwanted interactions. The aim of this study was to investigate the effects of clemastine on the expression and function of P-gp. MATERIALS AND METHODS: The effect of clemastine on P-gp function and expression was evaluated in vitro byrhodamine-123 (Rho(123)) efflux assay in Caco-2 cells and Western blot analysis. Rat in situ single pass intestinal permeability model was used to investigate the clemastine effect on digoxin P(eff), as a known P-gp substrate. Digoxin levels in intestinal perfusates were assayed by high performance liquid chromatography (HPLC) method. RESULTS: The Caco-2 intracellular accumulation of Rho(123) in clemastine and verapamil treated cells was 90.8 ± 9.8 and 420.6±25.4 pg/mg protein, respectively which was significantly higher than that in control cells (50.2±6.0; P<0.05). Immunoblotting results indicated that clemastine decreased expression of P-gp in Caco-2 cells in vitro. More over effective intestinal permeability (P(eff)) of digoxin in the presence of clemastine, was significantly increased compare to control group. CONCLUSION: Findings of our study suggested dose dependent P-gp inhibition activity for clemastine in vitro and in situ. Therefore co-administration of clemastine with P-gp substrates may result in unwanted interactions and side effects. |
format | Online Article Text |
id | pubmed-4887716 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Mashhad University of Medical Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-48877162016-06-08 Inhibitory effect of clemastine on P-glycoprotein expression and function: an in vitro and in situ study Abbasi, Mehran Mesgari Valizadeh, Hadi Hamishekar, Hamed Mohammadnejad, Leila Zakeri-Milani, Parvin Iran J Basic Med Sci Original Article OBJECTIVE(S): Transporters have an important role in pharmacokinetics of drugs. Inhibition or induction of drug transporters activity can affect drug absorption, safety, and efficacy. P-glycoprotein (P-gp) is the most important membrane transporter that is responsible for active efflux of drugs. It is important to understand which drugs are substrates, inhibitors, or inducers of P-gp to minimize or avoid unwanted interactions. The aim of this study was to investigate the effects of clemastine on the expression and function of P-gp. MATERIALS AND METHODS: The effect of clemastine on P-gp function and expression was evaluated in vitro byrhodamine-123 (Rho(123)) efflux assay in Caco-2 cells and Western blot analysis. Rat in situ single pass intestinal permeability model was used to investigate the clemastine effect on digoxin P(eff), as a known P-gp substrate. Digoxin levels in intestinal perfusates were assayed by high performance liquid chromatography (HPLC) method. RESULTS: The Caco-2 intracellular accumulation of Rho(123) in clemastine and verapamil treated cells was 90.8 ± 9.8 and 420.6±25.4 pg/mg protein, respectively which was significantly higher than that in control cells (50.2±6.0; P<0.05). Immunoblotting results indicated that clemastine decreased expression of P-gp in Caco-2 cells in vitro. More over effective intestinal permeability (P(eff)) of digoxin in the presence of clemastine, was significantly increased compare to control group. CONCLUSION: Findings of our study suggested dose dependent P-gp inhibition activity for clemastine in vitro and in situ. Therefore co-administration of clemastine with P-gp substrates may result in unwanted interactions and side effects. Mashhad University of Medical Sciences 2016-04 /pmc/articles/PMC4887716/ /pubmed/27279987 Text en Copyright: © Iranian Journal of Basic Medical Sciences http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Abbasi, Mehran Mesgari Valizadeh, Hadi Hamishekar, Hamed Mohammadnejad, Leila Zakeri-Milani, Parvin Inhibitory effect of clemastine on P-glycoprotein expression and function: an in vitro and in situ study |
title | Inhibitory effect of clemastine on P-glycoprotein expression and function: an in vitro and in situ study |
title_full | Inhibitory effect of clemastine on P-glycoprotein expression and function: an in vitro and in situ study |
title_fullStr | Inhibitory effect of clemastine on P-glycoprotein expression and function: an in vitro and in situ study |
title_full_unstemmed | Inhibitory effect of clemastine on P-glycoprotein expression and function: an in vitro and in situ study |
title_short | Inhibitory effect of clemastine on P-glycoprotein expression and function: an in vitro and in situ study |
title_sort | inhibitory effect of clemastine on p-glycoprotein expression and function: an in vitro and in situ study |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4887716/ https://www.ncbi.nlm.nih.gov/pubmed/27279987 |
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