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Idiosyncratic Drug-Induced Liver Injury (IDILI): Potential Mechanisms and Predictive Assays
Idiosyncratic drug-induced liver injury (IDILI) is a significant source of drug recall and acute liver failure (ALF) in the United States. While current drug development processes emphasize general toxicity and drug metabolizing enzyme- (DME-) mediated toxicity, it has been challenging to develop co...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241492/ https://www.ncbi.nlm.nih.gov/pubmed/28133614 http://dx.doi.org/10.1155/2017/9176937 |
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author | Roth, Alexander D. Lee, Moo-Yeal |
author_facet | Roth, Alexander D. Lee, Moo-Yeal |
author_sort | Roth, Alexander D. |
collection | PubMed |
description | Idiosyncratic drug-induced liver injury (IDILI) is a significant source of drug recall and acute liver failure (ALF) in the United States. While current drug development processes emphasize general toxicity and drug metabolizing enzyme- (DME-) mediated toxicity, it has been challenging to develop comprehensive models for assessing complete idiosyncratic potential. In this review, we describe the enzymes and proteins that contain polymorphisms believed to contribute to IDILI, including ones that affect phase I and phase II metabolism, antioxidant enzymes, drug transporters, inflammation, and human leukocyte antigen (HLA). We then describe the various assays that have been developed to detect individual reactions focusing on each of the mechanisms described in the background. Finally, we examine current trends in developing comprehensive models for examining these mechanisms. There is an urgent need to develop a panel of multiparametric assays for diagnosing individual toxicity potential. |
format | Online Article Text |
id | pubmed-5241492 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-52414922017-01-29 Idiosyncratic Drug-Induced Liver Injury (IDILI): Potential Mechanisms and Predictive Assays Roth, Alexander D. Lee, Moo-Yeal Biomed Res Int Review Article Idiosyncratic drug-induced liver injury (IDILI) is a significant source of drug recall and acute liver failure (ALF) in the United States. While current drug development processes emphasize general toxicity and drug metabolizing enzyme- (DME-) mediated toxicity, it has been challenging to develop comprehensive models for assessing complete idiosyncratic potential. In this review, we describe the enzymes and proteins that contain polymorphisms believed to contribute to IDILI, including ones that affect phase I and phase II metabolism, antioxidant enzymes, drug transporters, inflammation, and human leukocyte antigen (HLA). We then describe the various assays that have been developed to detect individual reactions focusing on each of the mechanisms described in the background. Finally, we examine current trends in developing comprehensive models for examining these mechanisms. There is an urgent need to develop a panel of multiparametric assays for diagnosing individual toxicity potential. Hindawi Publishing Corporation 2017 2017-01-04 /pmc/articles/PMC5241492/ /pubmed/28133614 http://dx.doi.org/10.1155/2017/9176937 Text en Copyright © 2017 A. D. Roth and M.-Y. Lee. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Article Roth, Alexander D. Lee, Moo-Yeal Idiosyncratic Drug-Induced Liver Injury (IDILI): Potential Mechanisms and Predictive Assays |
title | Idiosyncratic Drug-Induced Liver Injury (IDILI): Potential Mechanisms and Predictive Assays |
title_full | Idiosyncratic Drug-Induced Liver Injury (IDILI): Potential Mechanisms and Predictive Assays |
title_fullStr | Idiosyncratic Drug-Induced Liver Injury (IDILI): Potential Mechanisms and Predictive Assays |
title_full_unstemmed | Idiosyncratic Drug-Induced Liver Injury (IDILI): Potential Mechanisms and Predictive Assays |
title_short | Idiosyncratic Drug-Induced Liver Injury (IDILI): Potential Mechanisms and Predictive Assays |
title_sort | idiosyncratic drug-induced liver injury (idili): potential mechanisms and predictive assays |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241492/ https://www.ncbi.nlm.nih.gov/pubmed/28133614 http://dx.doi.org/10.1155/2017/9176937 |
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