Predictive value of in vitro safety studies.
The predictive value of in vitro safety studies is discussed for three important areas of pharmaceutical safety evaluations. In genetic toxicology, currently assays are sensitive for the prediction of cancer, but their overall predictive value is strongly diminished because of their low specificity. In the area of safety pharmacology blockage of hERG channel in vitro has recently been introduced to predict cardiac repolarization delay (QT interval prolongation) in patients. There is a plethora of in vitro methods to predict and characterize liver toxicity. However, little data is available that demonstrate a reliable prediction for hepatotoxicity in vivo over a wide range of chemical structures. In all three areas, further improvements are needed. 'Omics' technologies and new cell lines derived from stem cells are expected to strongly contribute to establish new and more predictive in vitro assays.
Suter
Willi
W
Exploratory Development, Safety Profiling and Assessment, Novartis Pharma AG, CH 4002 Basel, Switzerland. willi.suter@novartis.com
D000818:Animals; D004249:DNA Damage; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D008099:Liver / Q000187:drug effects; D011237:Predictive Value of Tests; D018675:Toxicity Tests / Q000379:methods*