About this Research Topic
The main focus of safety pharmacology since its inception has been assessing drug-induced prolongation in the QT interval - a surrogate biomarker for torsades de pointes (TdP) liability. Because the vast majority of drugs that can cause QT prolongation inhibit hERG channels, current regulatory guidelines concerning cardiac safety recommend that all compounds are subject to an in vitro evaluation of hERG block together with assessment of in vivo QT interval prolongation in an appropriate animal model and in humans. However, it has now become apparent that QT prolongation and hERG block are an insufficient proxy for TdP risk, and that the current approach based on these markers might even lead to withdrawal from the drug development pipeline and clinical use of potentially safe drugs. Safety pharmacology has broadened its interests in recent years to the whole cardiovascular, respiratory, and central nervous systems, and is now extending to other body functions. The discipline has evolved to identify and incorporate new technologies for clinical and non-clinical applications, including refinement of in vitro assays and screens, in vivo models, non-invasive clinical modalities, and in silico approaches. Here we collect a series of review and original research articles that summarize the state of our knowledge and the latest advances in these technologies, and how these might contribute in shaping new and improved cardiac safety guidelines.
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