Back to Search
Start Over
Key Challenges and Opportunities Associated with the Use of In Vitro Models to Detect Human DILI: Integrated Risk Assessment and Mitigation Plans
- Source :
- BioMed Research International, Vol 2016 (2016), BioMed Research International
- Publication Year :
- 2016
- Publisher :
- Hindawi Limited, 2016.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
General Immunology and Microbiology
business.industry
Market Withdrawal
lcsh:R
Liver failure
Data interpretation
lcsh:Medicine
Harmonization
General Medicine
Review Article
General Biochemistry, Genetics and Molecular Biology
3. Good health
Toxicology
03 medical and health sciences
030104 developmental biology
Risk analysis (engineering)
Key (cryptography)
Medicine
Drug reaction
business
Risk assessment
Pharmaceutical industry
Subjects
Details
- Language :
- English
- ISSN :
- 23146141 and 23146133
- Volume :
- 2016
- Database :
- OpenAIRE
- Journal :
- BioMed Research International
- Accession number :
- edsair.doi.dedup.....5b1006a6af9c4a4623201f11ba379adb