A model-based assay design to reproduce in vivo patterns of acute drug-induced toxicity
Blank, Lars M.
Fluri, David A.
Kelm, Jens M.
- Journal Article
Rights / licenseCreative Commons Attribution 4.0 International
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) Show more
Journal / seriesArchives of Toxicology
Pages / Article No.
Organisational unit02207 - Functional Genomics Center Zürich / Functional Genomics Center Zürich
08828 - Schlapbach, Ralph (Tit.-Prof.)
MoreShow all metadata