Academic Journal
Drug‐induced QT interval shortening: potential harbinger of proarrhythmia and regulatory perspectives
| العنوان: | Drug‐induced QT interval shortening: potential harbinger of proarrhythmia and regulatory perspectives |
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| المؤلفون: | Shah, Rashmi R |
| المصدر: | British Journal of Pharmacology ; volume 159, issue 1, page 58-69 ; ISSN 0007-1188 1476-5381 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2010 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | ATP‐dependent potassium channel openers such as pinacidil and levcromakalim have long been known to shorten action potential duration and to be profibrillatory in non‐clinical models, raising concerns on the clinical safety of drugs that shorten QT interval. Routine non‐clinical evaluation of new drugs for their potential to affect cardiac repolarization has revealed that drugs may also shorten QT interval. The description of congenital short QT syndrome in 2000, together with the associated arrhythmias, suggests that drug‐induced short QT interval may be proarrhythmic, and an uncanny parallel is evolving between our appreciation of the short and the long QT intervals. Epidemiological studies report an over‐representation of short QT interval values in patients with idiopathic ventricular fibrillation. Therefore, as new compounds that shorten QT interval are progressed further into clinical development, questions will inevitably arise on their safety. Arising from the current risk‐averse clinical and regulatory environment and concerns on proarrhythmic safety of drugs, together with our lack of a better understanding of the clinical significance of short QT interval, new drugs that substantially shorten QT interval will likely receive an unfavourable regulatory review unless these drugs fulfil an unmet clinical need. This review provides estimates of parameters of QT shortening that may be of potential clinical significance. Rufinamide, a recently approved anticonvulsant, illustrates the current regulatory approach to drugs that shorten QT interval. However, to further substantiate or confirm the safety of these drugs, their approval may well be conditional upon large‐scale post‐marketing studies with a focus on cardiac safety. This article is commented on by Malik, pp. 70–76 of this issue and is part of a themed section on QT safety. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2010 |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1111/j.1476-5381.2009.00191.x |
| الاتاحة: | https://doi.org/10.1111/j.1476-5381.2009.00191.x https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1476-5381.2009.00191.x https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.2009.00191.x |
| Rights: | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: | edsbas.FAD907FB |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/j.1476-5381.2009.00191.x |
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