ArticleDrug safety2006
Evaluation of the rabbit Purkinje fibre assay as an in vitro tool for assessing the risk of drug-induced torsades de pointes in humans.
Article in Drug safety, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 41 citations in OpenAlex.
- Knock-in Kcnh2 rabbit model of long QT syndrome type-2, epilepsy, and sudden death.Journal of translational medicine · 2025Article
- Comprehensive in vitro pro-arrhythmic assays demonstrate that omecamtiv mecarbil has low pro-arrhythmic risk.Clinical and translational science · 2021Article
- Comparison of electrophysiological effects of calcium channel blockers on cardiac repolarization.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2016Article
- Field and action potential recordings in heart slices: correlation with established in vitro and in vivo models.British journal of pharmacology · 2012Article
- Probucol is anti-hyperalgesic in a mouse peripheral nerve injury model of neuropathic pain.Neurobiology of pain (Cambridge, Mass.)Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe issue of drug-induced QT interval prolongation and torsades de pointes represents a major concern for pharmaceutical development. In this investigation, we examined the value of the isolated rabbit Purkinje fibre as an in vitro action potential (AP) assay to predict the potential of drugs to induce these undesirable adverse effects.
methodsFirst, we categorised the proarrhythmic risk of 26 medicinal products based on proportional reporting ratios for these two adverse events recorded in a US FDA database (Spontaneous Reporting System/Adverse Event Reporting System). Second, we measured drug effects on AP in rabbit Purkinje fibres. Finally, the results of the two analyses were compared to evaluate the predictive value of the in vitro assay.
resultsAnalysis of the clinical data classified the drugs into 14 positive, 7 negative and 5 questionable for proarrhythmic risk. Based on in vitro electrophysiological profiles, the drugs were grouped into four categories: (i) profile 1 drugs prolong repolarisation without slowing depolarisation; (ii) profile 2 drugs prolong repolarisation and also slow depolarisation; (iii) profile 3 drugs shorten repolarisation; and (iv) profile 4 drugs are without effects. All 14 clinical-positive drugs fell into profiles 1 or 2 (prolongers) with low safety margins (except probucol, which showed no effect, probably because of its low solubility). Clinical-negative drugs belonged mostly to profiles 3 or 4 (non-prolongers) [except clemastine and amlodipine, which were prolongers but had large safety margins]. Clinical-questionable drugs either did not prolong or prolonged slightly but produced additional electrophysiological effects opposing prolongation.
conclusionThe rabbit Purkinje fibre is a valuable assay for evaluating the proarrhythmic liability of pharmaceuticals as it can reveal complex electrophysiological profiles that modulate repolarisation delay.
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