A model-based assay design to reproduce in vivo patterns of acute drug-induced toxicity.
File(s)10.1007_s00204-017-2041-7.pdf (668.95 KB)
Published version
Author(s)
Type
Journal Article
Abstract
For more than a decade pharmaceutical R&D has been hampered by considerable attrition rates during clinical trials. The main reasons for drug failure is related to the lack of efficacy, limitations with respect to ADME (absorption, distribution, metabolism and excretion) properties, and—in approximately 30% of the cases—unforeseen toxicity (Kola and Landis 2004). The majority of adverse drug reactions observed in the clinical phase refer to organ injuries, e.g. of the cardiovascular system, the liver, the central nervous system and skeletal muscle (Cook et al. 2014). This clearly demonstrates the limited predictive accuracy of current preclinical models such as the rodent bioassay in evaluating repeated dose toxicity for predicting human toxic risks. It has been argued that overall, only 43% of toxic effects in humans may be correctly predicted by applying rodent-based safety evaluation protocols due to the fact that these assays tend to generate relatively large numbers of false negative as well as false positive read outs (Hartung 2009).
Date Issued
2017-08-29
Date Acceptance
2017-08-10
Citation
Archives of Toxicology, 2017, 92 (1), pp.553-555
ISSN
0340-5761
Publisher
Springer Verlag
Start Page
553
End Page
555
Journal / Book Title
Archives of Toxicology
Volume
92
Issue
1
Copyright Statement
© The Author(s) 2017. This article is an open access publication
License URL
Sponsor
Commission of the European Communities
Identifier
PII: 10.1007/s00204-017-2041-7
Grant Number
602156
Subjects
1115 Pharmacology And Pharmaceutical Sciences
Toxicology
Publication Status
Published