Assessing the proarrhythmic potential of drugs: current status of models and surrogate parameters of torsades de pointes arrhythmias

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Morten Bækgaard Thomsen, Jørgen Matz, Paul G A Volders, Marc A Vos

Torsades de pointes (TdP) is a potentially lethal cardiac arrhythmia that can occur as an unwanted adverse effect of various pharmacological therapies. Before a drug is approved for marketing, its effects on cardiac repolarisation are examined clinically and experimentally. This paper expresses the opinion that effects on repolarisation duration cannot directly be translated to risk of proarrhythmia. Current safety assessments of drugs only involve repolarisation assays, however the proarrhythmic profile can only be determined in the predisposed model. The availability of these proarrhythmic animal models is emphasised in the present paper. It is feasible for the pharmaceutical industry to establish one or more of these proarrhythmic animal models and large benefits are potentially available if pharmaceutical industries and patient-care authorities embraced these models. Furthermore, suggested surrogate parameters possessing predictive power of TdP arrhythmia are reviewed. As these parameters are not developed to finalisation, any meaningful study of the proarrhythmic potential of a new drug will include evaluation in an integrated model of TdP arrhythmia.
Original languageEnglish
JournalPharmacology & Therapeutics
Volume112
Issue number1
Pages (from-to)150-70
Number of pages21
ISSN0163-7258
DOIs
Publication statusPublished - Oct 2006

    Research areas

  • Animals, Disease Models, Animal, Humans, Pharmaceutical Preparations, Torsades de Pointes

ID: 45965579