Moving towards better predictors of drug-induced Torsade de Pointes. 2-3 November 2005, Crystal City, Virginia, USA

Expert Opinion on Drug Safety
Icilio Cavero, William Crumb

Abstract

The Health and Environmental Sciences Institute (HESI) convened a two-day workshop to explore the biological mechanisms responsible for inherited, acquired and induced long QT interval syndromes. Investigational areas included QT dynamics, cell biology, nonclinical models of Torsade de Pointes (TdP) arrhythmia as well as how to ascertain the predictability of such models for human outcome were discussed. Magisterial lectures from academia covered state-of-science knowledge on these domains, whereas industry and regulatory authority representatives dealt with the advantages, disadvantages and desirable requisites of nonclinical assays to assess drug-associated cardiac safety. Proposals for future research projects were not sufficiently factual to allow discrimination between pragmatic and ideal solutions. A key objective of the workshop was to foster initiatives addressing development of nonclinical proarrhythmic models for identifying without failure drug candidates with the potential to cause threshold QT interval increases of regulatory concern (5-10 ms) in healthy volunteers and a TdP event in 1/10(5)-10(7) patients. In the authors' opinion, fulfilling this goal (an FDA prerequisite for abrogating E14 'thorough QT study' req...Continue Reading

Citations

Mar 23, 2011·Journal of Pharmacological and Toxicological Methods·Kenny J WatsonPiet H Van Der Graaf
Mar 11, 2008·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Emanuel RaschiFabrizio De Ponti
Nov 23, 2006·European Journal of Pharmacology·Michael W SchmittIcilio Cavero
Nov 14, 2006·Journal of Pharmacological and Toxicological Methods·Henry H HolzgrefeStephen K Durham
Jul 22, 2006·Journal of Pharmacological and Toxicological Methods·Henry H HolzgrefeStephen K Durham
Aug 1, 2006·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Tengxian LiuGan-Xin Yan
Mar 3, 2009·Drug Metabolism and Pharmacokinetics·Antoine SoubretAnna Georgieva
Jun 7, 2011·Journal of Pharmacological and Toxicological Methods·Marina Brockway, Robert Hamlin
Aug 5, 2017·Clinical and Translational Science·Kimberly E MaxfieldAmeeta Parekh
Jun 29, 2007·Drugs in R&D·Gilles Hanton

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