Drug-Induced Liver Injury: Mechanism-Informed Prediction in Drug Development

C. Goldring; R. Weaver; B. Kramer; U. Klingmueller; A. Oppelt; B. Van der Water; J. Commandeur; A. Guillouzo; D. Naisbitt; N. French; N. Kitteringham; C. Pridgeon; P. Knolle; J. Sidaway; R. Sison-Young; L. Kamalian; A. Mercer; L. Faulkner; R. Pieters; M. Ingelman-Sundberg; B. Kevin Park

doi:10.1016/B978-0-12-409547-2.12384-4

Drug-Induced Liver Injury: Mechanism-Informed Prediction in Drug Development

C. Goldring, R. Weaver, B. Kramer, U. Klingmueller, A. Oppelt, B. Van der Water, J. Commandeur, A. Guillouzo, D. Naisbitt, N. French, N. Kitteringham, C. Pridgeon, P. Knolle, J. Sidaway, R. Sison-Young, L. Kamalian, A. Mercer, L. Faulkner, R. Pieters, M. Ingelman-SundbergB. Kevin Park

Institute of Molecular Immunology

Research output: Chapter in Book/Report/Conference proceeding › Chapter › peer-review

2 Scopus citations

Abstract

Drug-induced liver injury (DILI) is a significant clinical problem in terms of patient morbidity and mortality and also represents a challenge for the pharmaceutical industry leading to attrition of drugs in development and withdrawal of drugs post-licencing. The Innovative Medicines Initiative MIP-DILI Consortium details in this review the predominant mechanisms underlying DILI in order to help guide the development of physiologically, pharmacologically, and toxicologically relevant in vitro and in vivo DILI models. The overall thesis of this perspective is that only through a more comprehensive understanding of the mechanisms of human DILI will we be able to improve our efforts in the application of more meaningful models in the laboratory and thereby improve human prediction.

Original language	English
Title of host publication	Experimental Adme and Toxicology
Publisher	Elsevier Inc.
Pages	217-238
Number of pages	22
Volume	4-8
ISBN (Electronic)	9780128032008
ISBN (Print)	9780128032015
DOIs	https://doi.org/10.1016/B978-0-12-409547-2.12384-4
State	Published - 3 Jun 2017

Keywords

DILI
Drug
Endoplasmic reticulum
Immune
In vitro models
Liver
Lysosome
Mitochondria
Modeling
Reactive metabolites
Toxicity
Translation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/B978-0-12-409547-2.12384-4

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Goldring, C., Weaver, R., Kramer, B., Klingmueller, U., Oppelt, A., Van der Water, B., Commandeur, J., Guillouzo, A., Naisbitt, D., French, N., Kitteringham, N., Pridgeon, C., Knolle, P., Sidaway, J., Sison-Young, R., Kamalian, L., Mercer, A., Faulkner, L., Pieters, R., ... Kevin Park, B. (2017). Drug-Induced Liver Injury: Mechanism-Informed Prediction in Drug Development. In Experimental Adme and Toxicology (Vol. 4-8, pp. 217-238). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-409547-2.12384-4

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abstract = "Drug-induced liver injury (DILI) is a significant clinical problem in terms of patient morbidity and mortality and also represents a challenge for the pharmaceutical industry leading to attrition of drugs in development and withdrawal of drugs post-licencing. The Innovative Medicines Initiative MIP-DILI Consortium details in this review the predominant mechanisms underlying DILI in order to help guide the development of physiologically, pharmacologically, and toxicologically relevant in vitro and in vivo DILI models. The overall thesis of this perspective is that only through a more comprehensive understanding of the mechanisms of human DILI will we be able to improve our efforts in the application of more meaningful models in the laboratory and thereby improve human prediction.",

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author = "C. Goldring and R. Weaver and B. Kramer and U. Klingmueller and A. Oppelt and {Van der Water}, B. and J. Commandeur and A. Guillouzo and D. Naisbitt and N. French and N. Kitteringham and C. Pridgeon and P. Knolle and J. Sidaway and R. Sison-Young and L. Kamalian and A. Mercer and L. Faulkner and R. Pieters and M. Ingelman-Sundberg and {Kevin Park}, B.",

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Goldring, C, Weaver, R, Kramer, B, Klingmueller, U, Oppelt, A, Van der Water, B, Commandeur, J, Guillouzo, A, Naisbitt, D, French, N, Kitteringham, N, Pridgeon, C, Knolle, P, Sidaway, J, Sison-Young, R, Kamalian, L, Mercer, A, Faulkner, L, Pieters, R, Ingelman-Sundberg, M & Kevin Park, B 2017, Drug-Induced Liver Injury: Mechanism-Informed Prediction in Drug Development. in Experimental Adme and Toxicology. vol. 4-8, Elsevier Inc., pp. 217-238. https://doi.org/10.1016/B978-0-12-409547-2.12384-4

TY - CHAP

T1 - Drug-Induced Liver Injury

T2 - Mechanism-Informed Prediction in Drug Development

AU - Goldring, C.

AU - Weaver, R.

AU - Kramer, B.

AU - Klingmueller, U.

AU - Oppelt, A.

AU - Van der Water, B.

AU - Commandeur, J.

AU - Guillouzo, A.

AU - Naisbitt, D.

AU - French, N.

AU - Kitteringham, N.

AU - Pridgeon, C.

AU - Knolle, P.

AU - Sidaway, J.

AU - Sison-Young, R.

AU - Kamalian, L.

AU - Mercer, A.

AU - Faulkner, L.

AU - Pieters, R.

AU - Ingelman-Sundberg, M.

AU - Kevin Park, B.

PY - 2017/6/3

Y1 - 2017/6/3

N2 - Drug-induced liver injury (DILI) is a significant clinical problem in terms of patient morbidity and mortality and also represents a challenge for the pharmaceutical industry leading to attrition of drugs in development and withdrawal of drugs post-licencing. The Innovative Medicines Initiative MIP-DILI Consortium details in this review the predominant mechanisms underlying DILI in order to help guide the development of physiologically, pharmacologically, and toxicologically relevant in vitro and in vivo DILI models. The overall thesis of this perspective is that only through a more comprehensive understanding of the mechanisms of human DILI will we be able to improve our efforts in the application of more meaningful models in the laboratory and thereby improve human prediction.

AB - Drug-induced liver injury (DILI) is a significant clinical problem in terms of patient morbidity and mortality and also represents a challenge for the pharmaceutical industry leading to attrition of drugs in development and withdrawal of drugs post-licencing. The Innovative Medicines Initiative MIP-DILI Consortium details in this review the predominant mechanisms underlying DILI in order to help guide the development of physiologically, pharmacologically, and toxicologically relevant in vitro and in vivo DILI models. The overall thesis of this perspective is that only through a more comprehensive understanding of the mechanisms of human DILI will we be able to improve our efforts in the application of more meaningful models in the laboratory and thereby improve human prediction.

KW - DILI

KW - Drug

KW - Endoplasmic reticulum

KW - Immune

KW - In vitro models

KW - Liver

KW - Lysosome

KW - Mitochondria

KW - Modeling

KW - Reactive metabolites

KW - Toxicity

KW - Translation

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M3 - Chapter

AN - SCOPUS:85046146438

SN - 9780128032015

VL - 4-8

SP - 217

EP - 238

BT - Experimental Adme and Toxicology

PB - Elsevier Inc.

ER -

Drug-Induced Liver Injury: Mechanism-Informed Prediction in Drug Development

Abstract

Keywords

UN SDGs

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