Abstract
The success of an oral drug route administration depends on many factors that interfere in its bioavailability, therapeutic efficacy and clinical safety. In human cells, ATP-dependent efflux transporter proteins, such as P-glycoprotein (P-gp), BCRP and MRP2, reduce the absorption of drugs. A tiered approach chosen to evaluate drugs as substrates or inhibitors of efflux pumps, particularly P-gp, should be carefully selected, since each study method has advantages and intrinsic limitations to their processes. Depending on the adopted study conditions, the results may not correspond to the real characteristics of the drug regarding to its modulation by specific efflux proteins. This mini-review aims at summarizing the role of P-gp in the drugs oral absorption and correlating some of the most used permeability methods to determine the drug condition as P-gp substrate. Studies about P-gp have shown that it is a dynamic protein, facilitating secretion of endogenous compounds, as aldosterone, and protecting cells against xenobiotics. Different efflux assays are employed to evaluate drugs as P-gp substrates. In an initial planning, MDCK-MDR1 tend to be the chosen method for efflux studies due its ability of express P-gp, followed by studies conducted in Caco-2 models. However, it is necessary to evaluate the advantages and disadvantages of each method to generate sound results and to set the correlation in vitro x in situ x in vivo.
Keywords: Caco-2, drug permeability, efflux, ex vivo, in situ, in vitro, MDCK, MDCK-MDR1, P-glycoprotein.
Mini-Reviews in Medicinal Chemistry
Title:Evaluating Potential P-gp Substrates: Main Aspects to Choose the Adequate Permeability Model for Assessing Gastrointestinal Drug Absorption
Volume: 15 Issue: 10
Author(s): Joao Batista da Silva Junior, Thaisa Marinho Dezani, Andre Bersani Dezani and Cristina Helena dos Reis Serra
Affiliation:
Keywords: Caco-2, drug permeability, efflux, ex vivo, in situ, in vitro, MDCK, MDCK-MDR1, P-glycoprotein.
Abstract: The success of an oral drug route administration depends on many factors that interfere in its bioavailability, therapeutic efficacy and clinical safety. In human cells, ATP-dependent efflux transporter proteins, such as P-glycoprotein (P-gp), BCRP and MRP2, reduce the absorption of drugs. A tiered approach chosen to evaluate drugs as substrates or inhibitors of efflux pumps, particularly P-gp, should be carefully selected, since each study method has advantages and intrinsic limitations to their processes. Depending on the adopted study conditions, the results may not correspond to the real characteristics of the drug regarding to its modulation by specific efflux proteins. This mini-review aims at summarizing the role of P-gp in the drugs oral absorption and correlating some of the most used permeability methods to determine the drug condition as P-gp substrate. Studies about P-gp have shown that it is a dynamic protein, facilitating secretion of endogenous compounds, as aldosterone, and protecting cells against xenobiotics. Different efflux assays are employed to evaluate drugs as P-gp substrates. In an initial planning, MDCK-MDR1 tend to be the chosen method for efflux studies due its ability of express P-gp, followed by studies conducted in Caco-2 models. However, it is necessary to evaluate the advantages and disadvantages of each method to generate sound results and to set the correlation in vitro x in situ x in vivo.
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da Silva Junior Batista Joao, Dezani Marinho Thaisa, Dezani Bersani Andre and dos Reis Serra Helena Cristina, Evaluating Potential P-gp Substrates: Main Aspects to Choose the Adequate Permeability Model for Assessing Gastrointestinal Drug Absorption, Mini-Reviews in Medicinal Chemistry 2015; 15 (10) . https://dx.doi.org/10.2174/1389557515666150511152705
DOI https://dx.doi.org/10.2174/1389557515666150511152705 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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