Rechanneling the cardiac proarrhythmia safety paradigm: A meeting report from the Cardiac Safety Research Consortium

American Heart Journal

Volumn 167, Issue 3, 2014, Pages 292-300

  Sager, Philip T ^a   Gintant, Gary ^b   Turner, J Rick ^c   Pettit, Syril ^d   Stockbridge, Norman ^e  

^a STANFORD UNIVERSITY   (United States)

^b ABBVIE INC   (United States)

^c IQVIA   (United States)

^d ILSI HEALTH AND ENVIRONMENTAL SCIENCES INSTITUTE   (United States)

^e CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMIODARONE; CALCIUM; ION CHANNEL; PHENOBARBITAL; RANOLAZINE; SODIUM; TOLTERODINE;

ARTICLE; ATRIOVENTRICULAR CONDUCTION; CARDIOVASCULAR RISK; CHEMICAL STRUCTURE; CIRCADIAN RHYTHM; HEART DEPOLARIZATION; HEART ELECTROPHYSIOLOGY; HEART MUSCLE POTENTIAL; HEART PROARRHYTHMIA; HEART RATE; HEART REPOLARIZATION; HETEROLOGOUS EXPRESSION; HUMAN; IN VITRO STUDY; LONG QT SYNDROME 2; MEDICAL LITERATURE; PHASE 1 CLINICAL TRIAL (TOPIC); PLURIPOTENT STEM CELL; POTASSIUM CURRENT; PRIORITY JOURNAL; QT INTERVAL; QT PROLONGATION; SAFETY; SODIUM CURRENT; SUDDEN DEATH; VOLTAGE CLAMP TECHNIQUE;

ARRHYTHMIAS, CARDIAC; DRUG EVALUATION, PRECLINICAL; DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS; HUMANS; LONG QT SYNDROME; PATCH-CLAMP TECHNIQUES; RISK ASSESSMENT; TORSADES DE POINTES; UNITED STATES;

EID: 84896692500     PISSN: 00028703     EISSN: 10976744     Source Type: Journal    
DOI: 10.1016/j.ahj.2013.11.004     Document Type: Review

References (37)

1. Cardiac Safety Research Consortium Web site Available at: https://www.cardiac-safety.org/(Accessed 16th September 2013)
2. J. Finkle, D. Bloomfield, and K. Uhl et al. New precompetitive paradigms: focus on cardiac safety Am Heart J 157 2009 825 826
3. Health and Environmental Sciences Institute Available at: http://www.hesiglobal.org/i4a/pages/index.cfm?pageid=1 (Accessed 29th June, 2013)
4. ICH. Harmonised Tripartite Guideline S7B. Non-clinical evaluation of the potential for delayed ventricular repolarization (QT interval prolongation) by human pharmaceuticals. Step 4 Version, May 2005 Available at: http://www.ich.org/fileadmin/Public-Web-Site/ICH-Products/Guidelines/Safety/S7B/ Step4/S7B-Guideline.pdf (Accessed 28 June 2013)
5. ICH. Harmonised Tripartite Guideline E14. Clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs. Step 4 Version, May 2005 Available at: http://www.ich.org/fileadmin/Public-Web- Site/ICH-Products/Guidelines/Efficacy/E14/E14-Guideline.pdf (Accessed 28 June 2013)
6. E14 Implementation Working Group Harmonised Tripartite Guideline E14 Questions & Answers Document(R1). Clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs: Questions & Answers. Step 4 Version, April 2012 Available at: http://www.ich.org/ fileadmin/Public-Web-Site/ICH-Products/Guidelines/Efficacy/E14/ E14-Q-As-R1-step4.pdf (Accessed 28 June 2013)
7. ICH Available at: http://www.ich.org/(Accessed September 16 2013)
8. B.R. Berridge, P. Hoffmann, and J.R. Turk et al. Integrated and translational nonclinical in vivo cardiovascular risk assessment: gaps and opportunities Regul Toxicol Pharmacol 65 2013 38 46
9. P.T. Sager Key clinical considerations for demonstrating the utility of preclinical models to predict clinical drug-induced torsades de pointes Br J Pharmacol 154 2008 1544 1549
10. N. Stockbridge, J. Morganroth, R.R. Shah, and C. Garnett Dealing with global safety issues: was the response to QT-liability of non-cardiac drugs well coordinated? Drug Saf 36 2013 167 182
11. J.R. Turner, S. Kothari, and C.H. Cabell et al. Fifteen years of cardiac safety: history, state-of-the-art research, and glimpses into the future. 2013 International Pharmaceutical Industry 5 1 2013 110 119
12. F. De Ponti Pharmacological and regulatory aspects of QT prolongation R.J. Vaz, T. Klabunde, Antitargets: prediction and prevention of drug side effects 2008 Wiley-VCH Weinheim, Germany 55 88
13. S. Zhang, Z. Zhou, and Q. Gong et al. Mechanism of block and identification of the verapamil binding domain to HERG potassium channels Circ Res 84 1999 989 998
14. A. Bril, B. Gout, and M. Bonhomme et al. Combined potassium and calcium channel blocking activities as a basis for antiarrhythmic efficacy with low proarrhythmic risk: experimental profile of BRL-32872 J Pharmacol Exp Ther 276 1996 637 646
15. R.L. Martin, J.S. McDermott, and H.J. Salmen et al. The utility of hERG and repolarization assays in evaluating delayed cardiac repolarization: influence of multi-channel block J Cardiovasc Pharmacol 43 2004 369 379
16. G. Gintant An evaluation of hERG current assay performance: translating preclinical safety studies to clinical QT prolongation Pharmacol Ther 129 2011 109 119
17. J. Kramer, C.A. Obejero-Paz, and G. Myatt et al. MICE models: superior to the HERG model in predicting Torsade de Pointes Sci Rep 3 2013 2100
18. M.R. Davies, H.B. Mistry, and L. Hussein et al. An in silico canine cardiac midmyocardial action potential duration model as a tool for early drug safety assessment Am J Physiol Heart Circ Physiol 302 2012 466 480
19. P. Kannankeril, D.M. Roden, and D. Darbar Drug-induced long QT syndrome Pharmacol Rev 62 2010 760 781
20. G.Y. Di Veroli, M.R. Davies, and H. Zhang et al. High-throughput screening of drug-binding dynamics to HERG improves early drug safety assessment Am J Physiol Heart Circ Physiol 304 2013 H104 H117
21. T.J. Dale, C. Townsend, and E.C. Hollands et al. Population patch clamp electrophysiology: a breakthrough technology for ion channel screening Mol Biosyst 3 2007 714 722
22. N. Castle, D. Printzenhoff, and S. Zellmer et al. Sodium channel inhibitor drug discovery using automated high throughput electrophysiology platforms Comb Chem High Throughput Screen 12 2009 107 122
23. J. Ma, L. Guo, and S.J. Fiene et al. High purity human-induced pluripotent stem cell-derived cardiomyocytes: electrophysiological properties of action potentials and ionic currents Am J Physiol Heart Circ Physiol 301 2011 H2006 H2017
24. C. Farre, and N. Fertig HTS techniques for patch clamp-based ion channel screening-advances and economy Expert Opin Drug Discov. 7 2012 515 524
25. G.R. Mirams, Y. Cui, and A. Sher et al. Simulation of multiple ion channel block provides improved early prediction of compounds' clinical torsadogenic risk Cardiovasc Res 91 2011 53 61
26. J.P. Valentin, and T. Hammond Safety and secondary pharmacology: successes, threats, challenges and opportunities J Pharmacol Toxicol Methods 58 2008 77 87
27. K. Fletcher, R.R. Shah, and A. Thomas et al. Novel approaches to assessing cardiac safety-proceedings of a workshop: regulators, industry and academia discuss the future of in silico cardiac modelling to predict the proarrhythmic safety of drugs Drug Saf 34 2011 439 443
28. G.R. Mirams, M.R. Davies, and Y. Cui et al. Application of cardiac electrophysiology simulations to pro-arrhythmic safety testing Br J Pharmacol 167 2012 932 945
29. K.A. Beattie, C. Luscombe, and G. Williams et al. Evaluation of an in silico cardiac safety assay: using ion channel screening data to predict QT interval changes in the rabbit ventricular wedge J Pharmacol Toxicol Methods 68 2013 88 96
30. T. O'Hara, L. Virág, and A. Varró et al. Simulation of the undiseased human cardiac ventricular action potential: model formulation and experimental validation PLoS Comput Biol 7 5 2011 e100206121
31. N.M. Mordwinkin, P.W. Burridge, and J.C. Wu A review of human pluripotent stem cell-derived cardiomyocytes for high-throughput drug discovery, cardiotoxicity screening, and publication standards J Cardiovasc Transl Res 6 2013 22 30
32. M. Hoekstra, C.L. Mummery, and A.A. Wilde et al. Induced pluripotent stem cell derived cardiomyocytes as models for cardiac arrhythmias Front Physiol 3 2012 346 eCollection 2012
33. S. Peng, A.E. Lacerda, and G.E. Kirsch et al. The action potential and comparative pharmacology of stem cell-derived human cardiomyocytes J Pharmacol Toxicol Methods 61 2010 277 286
34. M.K. Jonsson, M.A. Vos, and G.R. Mirams et al. Application of human stem cell-derived cardiomyocytes in safety pharmacology requires caution beyond hERG J Mol Cell Cardiol 52 2012 998 1008
35. Y. Qu, B. Gao, and M. Fang et al. Human embryonic stem cell derived cardiac myocytes detect hERG-mediated repolarization effects, but not Nav1.5 induced depolarization delay J Pharmacol Toxicol Methods 68 2013 74 81
36. Turner JR, Panicker GK, Karnad DR, et al. Cardiovascular safety monitoring during oncology drug development and therapy. Am J Ther, in press.
37. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction N Engl J Med 321 1989 406 412