Key Challenges and Opportunities Associated with the Use of In Vitro Models to Detect Human DILI: Integrated Risk Assessment and Mitigation Plans
Joint Authors
Chen, Minjun
Atienzar, Franck A.
Blomme, Eric A.
Hewitt, Philip
Kenna, J. Gerry
Labbe, Gilles
Moulin, Frederic
Pognan, Francois
Roth, Adrian B.
Suter-Dick, Laura
Ukairo, Okechukwu
Weaver, Richard J.
Will, Yvonne
Dambach, Donna M.
Source
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-20, 20 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-09-05
Country of Publication
Egypt
No. of Pages
20
Main Subjects
Abstract EN
Drug-induced liver injury (DILI) is a major cause of late-stage clinical drug attrition, market withdrawal, black-box warnings, and acute liver failure.
Consequently, it has been an area of focus for toxicologists and clinicians for several decades.
In spite of considerable efforts, limited improvements in DILI prediction have been made and efforts to improve existing preclinical models or develop new test systems remain a high priority.
While prediction of intrinsic DILI has improved, identifying compounds with a risk for idiosyncratic DILI (iDILI) remains extremely challenging because of the lack of a clear mechanistic understanding and the multifactorial pathogenesis of idiosyncratic drug reactions.
Well-defined clinical diagnostic criteria and risk factors are also missing.
This paper summarizes key data interpretation challenges, practical considerations, model limitations, and the need for an integrated risk assessment.
As demonstrated through selected initiatives to address other types of toxicities, opportunities exist however for improvement, especially through better concerted efforts at harmonization of current, emerging and novel in vitro systems or through the establishment of strategies for implementation of preclinical DILI models across the pharmaceutical industry.
Perspectives on the incorporation of newer technologies and the value of precompetitive consortia to identify useful practices are also discussed.
American Psychological Association (APA)
Atienzar, Franck A.& Blomme, Eric A.& Chen, Minjun& Hewitt, Philip& Kenna, J. Gerry& Labbe, Gilles…[et al.]. 2016. Key Challenges and Opportunities Associated with the Use of In Vitro Models to Detect Human DILI: Integrated Risk Assessment and Mitigation Plans. BioMed Research International،Vol. 2016, no. 2016, pp.1-20.
https://search.emarefa.net/detail/BIM-1099368
Modern Language Association (MLA)
Atienzar, Franck A.…[et al.]. Key Challenges and Opportunities Associated with the Use of In Vitro Models to Detect Human DILI: Integrated Risk Assessment and Mitigation Plans. BioMed Research International No. 2016 (2016), pp.1-20.
https://search.emarefa.net/detail/BIM-1099368
American Medical Association (AMA)
Atienzar, Franck A.& Blomme, Eric A.& Chen, Minjun& Hewitt, Philip& Kenna, J. Gerry& Labbe, Gilles…[et al.]. Key Challenges and Opportunities Associated with the Use of In Vitro Models to Detect Human DILI: Integrated Risk Assessment and Mitigation Plans. BioMed Research International. 2016. Vol. 2016, no. 2016, pp.1-20.
https://search.emarefa.net/detail/BIM-1099368
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1099368