Atlantis Institut des Sciences Fictives

Resumen: 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...
Idioma: Inglés
DOI: 10.3389/fphys.2018.00678
Año: 2018
Publicado en: FRONTIERS IN PHYSIOLOGY 9 (2018), 678 [5 pp]
ISSN: 1664-042X
Factor impacto JCR: 3.201 (2018)
Categ. JCR: PHYSIOLOGY rank: 25 / 81 = 0.309 (2018) - Q2 - T1
Factor impacto SCIMAGO: 1.153 - Physiology (medical) (Q2) - Physiology (Q2)

Financiación: info:eu-repo/grantAgreement/ES/DGA-FEDER/T39-17R-BSICoS
Financiación: 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
Financiación: info:eu-repo/grantAgreement/ES/MINECO/DPI2016-75458-R
Tipo y forma: (Published version)
Área (Departamento): Área Teoría Señal y Comunicac. (Dpto. Ingeniería Electrón.Com.)
Exportado de SIDERAL (2021-08-20-08:36:33)


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