Here - Stiftung Forschung 3R

PREDICT-IV
Novel Alternative Testing Strategies for Use in
Pharmaceutical Discovery and Development
Contract number: HEALTH-FP5-2007-202222
Project type: Integrated Project (FP7)
EC contribution: € 11,330,907
Starting date: 1 May 2008
Duration:
60 months
Website: predict-iv.toxi.uni-wuerzburg.de
Background
In the development of new pharmaceutical entities, lead compounds are designed on
the basis of desired pharmacological effects. Often, many derivatives of these lead
compounds are synthesised early in the development for optimised pharmacological
response. Toxicity testing of the many compounds with the desired pharmacological
effects generated represents one of the bottlenecks in the development of new
pharmaceuticals. Toxicity testing is time consuming, requires a high number of
demanding in vitro and in vivo experiments, and large quantities of test compounds. In
addition to hazard assessment, the pharmacokinetics of such compounds are still mainly
investigated using animals to identify candidate compounds with the pharmacokinetic
properties desired.
Toxicity testing usually relies on the identification of certain histopathological changes
and clinical parameters and pathology in animals. Toxicity studies range in duration
from two weeks to two years and use 5 to 50 animals/dose groups, with usually three
dose groups and a vehicle control. From such studies, detailed information on adverse
effects and their dose-response is obtained, but the data generated require extrapolation
to the human situation. This extrapolation often fails.
The inclusion of biomarkers for undesired effects is not yet performed in many of the
routine toxicity studies, but biomarkers to predict toxicity for relevant target organs are
under development and are increasingly applied to predict possible toxicities in the
early phase of toxicity studies.
PROGRESS REPORTS FROM EU-FUNDED PROJECTS
Progress Report 2011 & AXLR8-2 Workshop Report
147