L M Hondeghem

Summary

Publications

  1. doi request reprint Domperidone: limited benefits with significant risk for sudden cardiac death
    Luc M Hondeghem
    Department of Pharmacology, Catholic University of Leuven, Leuven, Belgium
    J Cardiovasc Pharmacol 61:218-25. 2013
  2. doi request reprint Preclinical cardiovascular safety evaluations of biologics: optimizing the approach and follow-up
    Luc Hondeghem
    Department of Pharmacology, Catholic University Leuven, Belgium
    BioDrugs 26:275-82. 2012
  3. ncbi request reprint Low safety index of domperidone: mechanism for increased odds ratio for sudden cardiac death
    Luc M Hondeghem
    Dept of Pharmacology, K U Leuven, Leuven, Belgium
    Acta Cardiol 66:421-5. 2011
  4. doi request reprint Drug-induced QTC prolongation dangerously underestimates proarrhythmic potential: lessons from terfenadine
    Luc M Hondeghem
    Department of Pharmacology, KU Leuven, Leuven, Belgium
    J Cardiovasc Pharmacol 57:589-97. 2011
  5. doi request reprint Oscillations of cardiac wave length and proarrhythmia
    L M Hondeghem
    Department of Pharmacology, Catholic University, Leuven, Belgium
    Naunyn Schmiedebergs Arch Pharmacol 382:367-76. 2010
  6. doi request reprint QT prolongation is an unreliable predictor of ventricular arrhythmia
    Luc M Hondeghem
    Department of Pharmacology, Katholieke Universiteit Leuven, Leuven, Belgium
    Heart Rhythm 5:1210-2. 2008
  7. ncbi request reprint QT and TdP. QT: an unreliable predictor of proarrhythmia
    Luc M Hondeghem
    Dept of Pharmacology, KU Leuven, Leuven, Belgium
    Acta Cardiol 63:1-7. 2008
  8. doi request reprint Use and abuse of QT and TRIaD in cardiac safety research: importance of study design and conduct
    Luc M Hondeghem
    Catholic University Leuven, Westlaan 85, B 8400 Oostende, Belgium
    Eur J Pharmacol 584:1-9. 2008
  9. ncbi request reprint Short patent lives jeopardize drug and patient safety
    Luc M Hondeghem
    Department of Pharmacology, Catholic University of Leuven, Belgium
    J Cardiovasc Pharmacol 50:353-7. 2007
  10. ncbi request reprint Thorough QT/QTc not so thorough: removes torsadogenic predictors from the T-wave, incriminates safe drugs, and misses profibrillatory drugs
    Luc M Hondeghem
    Catholic University, Leuven, Belgium
    J Cardiovasc Electrophysiol 17:337-40. 2006

Detail Information

Publications17

  1. doi request reprint Domperidone: limited benefits with significant risk for sudden cardiac death
    Luc M Hondeghem
    Department of Pharmacology, Catholic University of Leuven, Leuven, Belgium
    J Cardiovasc Pharmacol 61:218-25. 2013
    ..Domperidone (antinausea/vomiting agent) was recently shown by several groups to increase sudden cardiac death (SCD). Drug-induced disturbances of cardiac repolarization may be a major mechanism...
  2. doi request reprint Preclinical cardiovascular safety evaluations of biologics: optimizing the approach and follow-up
    Luc Hondeghem
    Department of Pharmacology, Catholic University Leuven, Belgium
    BioDrugs 26:275-82. 2012
    ..However, because of the potential variability in composition of biologics between production batches and sources, evaluations of such products needs to be performed more frequently than for uniformly produced STA...
  3. ncbi request reprint Low safety index of domperidone: mechanism for increased odds ratio for sudden cardiac death
    Luc M Hondeghem
    Dept of Pharmacology, K U Leuven, Leuven, Belgium
    Acta Cardiol 66:421-5. 2011
    ..I therefore tested domperidone for liability of cardiac repolarization disturbances (triangulation, reverse use dependence, instability and dispersion or TRIaD) and induction of arrhythmias...
  4. doi request reprint Drug-induced QTC prolongation dangerously underestimates proarrhythmic potential: lessons from terfenadine
    Luc M Hondeghem
    Department of Pharmacology, KU Leuven, Leuven, Belgium
    J Cardiovasc Pharmacol 57:589-97. 2011
    ..Terfenadine's proarrhythmia prompted market withdrawal; therapeutic antihistaminic concentration is less than 1 nM, whereas IC50 of IKr and INa exceed 200 nM...
  5. doi request reprint Oscillations of cardiac wave length and proarrhythmia
    L M Hondeghem
    Department of Pharmacology, Catholic University, Leuven, Belgium
    Naunyn Schmiedebergs Arch Pharmacol 382:367-76. 2010
    ..Torsade de pointes can result not only from disturbances of repolarization but also from disturbances of conduction...
  6. doi request reprint QT prolongation is an unreliable predictor of ventricular arrhythmia
    Luc M Hondeghem
    Department of Pharmacology, Katholieke Universiteit Leuven, Leuven, Belgium
    Heart Rhythm 5:1210-2. 2008
    ..Cardiac safety is better evaluated in terms of lambda, TRIaD (Triangulation, Reverse use dependence, Instability, and Dispersion), and disturbances of automaticity...
  7. ncbi request reprint QT and TdP. QT: an unreliable predictor of proarrhythmia
    Luc M Hondeghem
    Dept of Pharmacology, KU Leuven, Leuven, Belgium
    Acta Cardiol 63:1-7. 2008
    ..In patients,TRIaD equivalents in the ECG may likewise be more important than QT interval...
  8. doi request reprint Use and abuse of QT and TRIaD in cardiac safety research: importance of study design and conduct
    Luc M Hondeghem
    Catholic University Leuven, Westlaan 85, B 8400 Oostende, Belgium
    Eur J Pharmacol 584:1-9. 2008
    ....
  9. ncbi request reprint Short patent lives jeopardize drug and patient safety
    Luc M Hondeghem
    Department of Pharmacology, Catholic University of Leuven, Belgium
    J Cardiovasc Pharmacol 50:353-7. 2007
    ..Therefore, we suggest that the potential benefits of patent life prolongation should be considered, under certain conditions for the sake of patient safety...
  10. ncbi request reprint Thorough QT/QTc not so thorough: removes torsadogenic predictors from the T-wave, incriminates safe drugs, and misses profibrillatory drugs
    Luc M Hondeghem
    Catholic University, Leuven, Belgium
    J Cardiovasc Electrophysiol 17:337-40. 2006
    ..Worse, available evidence suggests that there is more death from drug-induced fibrillation than TdP. Thus, QT prolongation alone is not very useful. Instead, the T-wave should be used in alternate ways: extraction of TRIaD...
  11. ncbi request reprint Instability and triangulation of the action potential predict serious proarrhythmia, but action potential duration prolongation is antiarrhythmic
    L M Hondeghem
    Department of Pharmacology, Leuven, Belgium
    Circulation 103:2004-13. 2001
    ..Prolongation of action potential duration (APD) is considered a major antiarrhythmic mechanism (class 2I), but paradoxically, it frequently is also proarrhythmic (torsade de pointes)...
  12. ncbi request reprint Phase 2 prolongation, in the absence of instability and triangulation, antagonizes class III proarrhythmia
    L M Hondeghem
    Department of Pharmacology, K U L, Leuven B 3000, Belgium
    Cardiovasc Res 50:345-53. 2001
    ..To evaluate whether prolongation of the plateau of the action potential duration, in the absence of instability and triangulation, can reverse the proarrhythmia elicited by a class III antiarrhythmic agent...
  13. ncbi request reprint Detection of proarrhythmia in the female rabbit heart: blinded validation
    Luc M Hondeghem
    Department of Pharmacology, K U Leuven, Leuven, Belgium
    J Cardiovasc Electrophysiol 14:287-94. 2003
    ..Reliable detection of drug-induced proarrhythmia, especially the potential for polymorphic ventricular tachycardia, is of great importance in the development of new compounds that are safe for the heart and was evaluated in a blinded study...
  14. ncbi request reprint Blinded test in isolated female rabbit heart reliably identifies action potential duration prolongation and proarrhythmic drugs: importance of triangulation, reverse use dependence, and instability
    Luc M Hondeghem
    Department of Pharmacology, Catholic University of Leuven, Leuven, Belgium
    J Cardiovasc Pharmacol 41:14-24. 2003
    ..Thus, the isolated perfused rabbit heart can be a valuable tool in a preclinical proarrhythmia test battery in drug development...
  15. ncbi request reprint Relative contributions of TRIaD and QT to proarrhythmia
    Luc M Hondeghem
    J Cardiovasc Electrophysiol 18:655-7. 2007
  16. ncbi request reprint TRIad: foundation for proarrhythmia (triangulation, reverse use dependence and instability)
    Luc M Hondeghem
    Novartis Found Symp 266:235-44; discussion 244-50. 2005
    ..It is concluded that proarrhythmic characteristics of drugs can readily be recognized and that hope exists for an effective and safe class III antiarrhythmic agent after all...
  17. ncbi request reprint Refining detection of drug-induced proarrhythmia: QT interval and TRIaD
    Rashmi R Shah
    Medicines and Healthcare products Regulatory Agency, London, UK
    Heart Rhythm 2:758-72. 2005
    ..Detecting drug-induced augmentation of TRIaD may offer an additional, more sensitive, and accurate indicator of the broader proarrhythmic potential of a drug than may QT interval prolongation alone...