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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7215464 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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