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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...

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Autores principales: Roth, Alexander D., Lee, Moo-Yeal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2017
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.
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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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