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Role of Genetic Variations in the Hepatic Handling of Drugs

The liver plays a pivotal role in drug handling due to its contribution to the processes of detoxification (phases 0 to 3). In addition, the liver is also an essential organ for the mechanism of action of many families of drugs, such as cholesterol-lowering, antidiabetic, antiviral, anticoagulant, a...

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Autores principales: Marin, Jose J. G., Serrano, Maria A., Monte, Maria J., Sanchez-Martin, Anabel, Temprano, Alvaro G., Briz, Oscar, Romero, Marta R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215464/
https://www.ncbi.nlm.nih.gov/pubmed/32326111
http://dx.doi.org/10.3390/ijms21082884
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author Marin, Jose J. G.
Serrano, Maria A.
Monte, Maria J.
Sanchez-Martin, Anabel
Temprano, Alvaro G.
Briz, Oscar
Romero, Marta R.
author_facet Marin, Jose J. G.
Serrano, Maria A.
Monte, Maria J.
Sanchez-Martin, Anabel
Temprano, Alvaro G.
Briz, Oscar
Romero, Marta R.
author_sort Marin, Jose J. G.
collection PubMed
description The liver plays a pivotal role in drug handling due to its contribution to the processes of detoxification (phases 0 to 3). In addition, the liver is also an essential organ for the mechanism of action of many families of drugs, such as cholesterol-lowering, antidiabetic, antiviral, anticoagulant, and anticancer agents. Accordingly, the presence of genetic variants affecting a high number of genes expressed in hepatocytes has a critical clinical impact. The present review is not an exhaustive list but a general overview of the most relevant variants of genes involved in detoxification phases. The available information highlights the importance of defining the genomic profile responsible for the hepatic handling of drugs in many ways, such as (i) impaired uptake, (ii) enhanced export, (iii) altered metabolism due to decreased activation of prodrugs or enhanced inactivation of active compounds, and (iv) altered molecular targets located in the liver due to genetic changes or activation/downregulation of alternative/compensatory pathways. In conclusion, the advance in this field of modern pharmacology, which allows one to predict the outcome of the treatments and to develop more effective and selective agents able to overcome the lack of effect associated with the existence of some genetic variants, is required to step forward toward a more personalized medicine.
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spelling pubmed-72154642020-05-22 Role of Genetic Variations in the Hepatic Handling of Drugs Marin, Jose J. G. Serrano, Maria A. Monte, Maria J. Sanchez-Martin, Anabel Temprano, Alvaro G. Briz, Oscar Romero, Marta R. Int J Mol Sci Review The liver plays a pivotal role in drug handling due to its contribution to the processes of detoxification (phases 0 to 3). In addition, the liver is also an essential organ for the mechanism of action of many families of drugs, such as cholesterol-lowering, antidiabetic, antiviral, anticoagulant, and anticancer agents. Accordingly, the presence of genetic variants affecting a high number of genes expressed in hepatocytes has a critical clinical impact. The present review is not an exhaustive list but a general overview of the most relevant variants of genes involved in detoxification phases. The available information highlights the importance of defining the genomic profile responsible for the hepatic handling of drugs in many ways, such as (i) impaired uptake, (ii) enhanced export, (iii) altered metabolism due to decreased activation of prodrugs or enhanced inactivation of active compounds, and (iv) altered molecular targets located in the liver due to genetic changes or activation/downregulation of alternative/compensatory pathways. In conclusion, the advance in this field of modern pharmacology, which allows one to predict the outcome of the treatments and to develop more effective and selective agents able to overcome the lack of effect associated with the existence of some genetic variants, is required to step forward toward a more personalized medicine. MDPI 2020-04-20 /pmc/articles/PMC7215464/ /pubmed/32326111 http://dx.doi.org/10.3390/ijms21082884 Text en © 2020 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 Review
Marin, Jose J. G.
Serrano, Maria A.
Monte, Maria J.
Sanchez-Martin, Anabel
Temprano, Alvaro G.
Briz, Oscar
Romero, Marta R.
Role of Genetic Variations in the Hepatic Handling of Drugs
title Role of Genetic Variations in the Hepatic Handling of Drugs
title_full Role of Genetic Variations in the Hepatic Handling of Drugs
title_fullStr Role of Genetic Variations in the Hepatic Handling of Drugs
title_full_unstemmed Role of Genetic Variations in the Hepatic Handling of Drugs
title_short Role of Genetic Variations in the Hepatic Handling of Drugs
title_sort role of genetic variations in the hepatic handling of drugs
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215464/
https://www.ncbi.nlm.nih.gov/pubmed/32326111
http://dx.doi.org/10.3390/ijms21082884
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