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- Title
The Use of Beat-to-Beat Electrocardiogram Analysis to Distinguish QT/QTc Interval Changes Caused by Moxifloxacin From Those Caused by Vardenafil.
- Authors
Fossa, A. A.; Langdon, G.; Couderc, J.-P.; Zhou, M.; Darpo, B.; Wilson, F.; Wallis, R.; Davis, J. D.
- Abstract
QT correction factors (QTc) can cause errors in the interpretation of drug effects on cardiac repolarization because they do not adequately differentiate changes when heart rate or autonomic state deviates from the baseline QT/RR interval relationship. The purpose of our study was to determine whether the new method of QT interval dynamic beat-to-beat (QTbtb) analysis could better discriminate between impaired repolarization caused by moxifloxacin and normal autonomic changes induced by subtle reflex tachycardia after vardenafil. Moxifloxacin produced maximum mean increases of 13-14 ms in QTbtb, QTcF, and QTcI after 4 h. After vardenafil administration, a 10-ms effect could be excluded at all time points with QTbtb but not with QTcF or QTcI. Subset analysis of the vardenafil upper pharmacokinetic quartile showed that the upper bound of QTcF and QTcI was >10 ms, whereas that of QTbtb was <8 ms. This study demonstrated that newer methods of electrocardiogram (ECG) analysis can differentiate changes in the QT interval to improve identification of proarrhythmia risk.
- Subjects
CORRECTION factors; PHARMACODYNAMICS; EFFECT of drugs on the heart; HEART beat; MOXIFLOXACIN; TACHYCARDIA; PHARMACOKINETICS; PROARRHYTHMIA
- Publication
Clinical Pharmacology & Therapeutics, 2011, Vol 90, Issue 3, p449
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1038/clpt.2011.139