75925 20210820090343.0 doi 10.3389/fphys.2018.00678 sideral 106846 ART-2018-106846 eng Grandi, E. Editorial: Safety Pharmacology - Risk Assessment QT Interval Prolongation and Beyond 2018 Access copy available to the general public Unrestricted The scope of safety pharmacology is to predict whether a drug is likely to cause potentially lethal adverse effects if administered to humans. While 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), a major focus 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 evaluated in vitro for their hERG inhibitory potency (Redfern et al., 2003) and in vivo for their ability to cause QT/QTc interval prolongation (Food and Drug Administration, 2005) in an appropriate animal model and in humans. However, it has now become apparent that QT/QTc prolongation and hERG block are an insufficient proxy for TdP risk. While the current approach based on these markers has been successful in terms of preventing TdP risk, this regulatory paradigm might lead to withdrawal from the drug development pipeline and clinical use of potentially safe drugs. There is therefore a crucial need to develop a more accurate assessment of proarrhythmic potential of drugs... info:eu-repo/grantAgreement/ES/DGA-FEDER/T39-17R-BSICoS info:eu-repo/grantAgreement/EC/H2020/638284/EU/Is your heart aging well? A systems biology approach to characterize cardiac aging from the cell to the body surface/MODELAGE This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 638284-MODELAGE info:eu-repo/grantAgreement/ES/MINECO/DPI2016-75458-R info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 3.201 2018 PHYSIOLOGY 25 / 81 = 0.309 2018 Q2 T1 1.153 2018 Physiology (medical) 2018 Q2 Physiology 2018 Q2 info:eu-repo/semantics/other info:eu-repo/semantics/publishedVersion Morotti, S. Pueyo, E. Universidad de Zaragoza (orcid)0000-0002-1960-407X Rodriguez, B. 5008 800 Universidad de Zaragoza Dpto. Ingeniería Electrón.Com. Área Teoría Señal y Comunicac. 9 (2018), 678 [5 pp] Front. physiol. FRONTIERS IN PHYSIOLOGY 1664-042X 186103 http://zaguan.unizar.es/record/75925/files/texto_completo.pdf Versión publicada 11276 http://zaguan.unizar.es/record/75925/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:75925 articulos driver 2021-08-20-08:36:33 ARTICLE