The combined use of ibutilide as an active control with intensive electrocardiographic sampling and signal averaging as a sensitive method to assess the effects of tadalafil on the human QT interval.

The combined use of ibutilide as an active control with intensive electrocardiographic sampling and signal averaging as a sensitive method to assess the effects of tadalafil on the human QT interval.

MedLine Citation:	PMID: 16098435 Owner: NLM Status: MEDLINE
Abstract/OtherAbstract:	OBJECTIVES: This study was designed to evaluate effects of tadalafil, a phosphodiesterase-5 inhibitor used for the treatment of erectile dysfunction (ED), on the QT interval. BACKGROUND: Cardiovascular disease is common in men with ED. Men with cardiovascular disease and ED may have decreased cardiac repolarization reserve. METHODS: Effects of tadalafil (100 mg by mouth), ibutilide (0.002 mg/kg intravenously), and placebo on the QT interval in healthy men were compared (placebo and tadalafil [n = 90], with a subset [n = 61] receiving all treatments; mean age 30 years, range 18 to 53 years). Electrocardiographic sampling was done for two days before treatment and on treatment days. The QT was corrected for RR interval with five correction methods, including an individual correction (QTcI). Plasma concentrations of tadalafil were measured to evaluate concentration-QT effect relationships. RESULTS: At the time corresponding to maximum plasma concentration of tadalafil, the mean difference in the change in QTcI between tadalafil and placebo was 2.8 ms; tadalafil was equivalent to placebo (a priori, upper limit of 90% confidence interval < 10 ms [actual = 4.4 ms]; post hoc, upper limit of 95% confidence interval < 5 ms [actual = 4.8]). The active control, ibutilide, significantly increased QTcI by 6.9 and 8.9 ms compared with tadalafil and placebo, respectively. Similar statistical results were obtained with four additional QT correction methods. No subject had a QTcI > or = 450 ms or an increase in QTcI > or = 30 ms with any treatment. CONCLUSIONS: Based on the a priori statistical test of equivalence, placebo and high-dose tadalafil produced equivalent effects on the QT interval. This study reliably discerned 5- to 10-ms changes in corrected QT in the ibutilide active control group.

Authors:	Charles M Beasley; Malcolm I Mitchell; Alex A Dmitrienko; Jeffrey T Emmick; Wei Shen; Timothy M Costigan; Alun W Bedding; Michael A Turik; Arash Bakhtyari; Margaret R Warner; Jeremy N Ruskin; Louis R Cantilena; Robert A Kloner
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Publication Detail:	Type: Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial
Journal Detail:	Title: Journal of the American College of Cardiology Volume: 46 ISSN: 0735-1097 ISO Abbreviation: J. Am. Coll. Cardiol. Publication Date: 2005 Aug
Date Detail:	Created Date: 2005-08-15 Completed Date: 2005-09-13 Revised Date: 2007-11-15
Medline Journal Info:	Nlm Unique ID: 8301365 Medline TA: J Am Coll Cardiol Country: United States
Other Details:	Languages: eng Pagination: 678-87 Citation Subset: AIM; IM
Affiliation:	Lilly Research Laboratories, Indianapolis, Indiana 46285, USA. cmbeasleyj@lilly.com
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MeSH Terms
Descriptor/Qualifier:	Adolescent Adult Anti-Arrhythmia Agents / pharmacology* Carbolines / adverse effects, pharmacology Case-Control Studies Electrocardiography Electrophysiology Erectile Dysfunction / drug therapy Humans Long QT Syndrome Male Middle Aged Phosphodiesterase Inhibitors / adverse effects, pharmacology Placebos Sulfonamides / pharmacology Time Factors Ventricular Function / drug effects*
Chemical
Reg. No./Substance:	0/Anti-Arrhythmia Agents; 0/Carbolines; 0/Phosphodiesterase Inhibitors; 0/Placebos; 0/Sulfonamides; 0/tadalafil; 130350-52-6/ibutilide
Comments/Corrections
Comment In:	J Am Coll Cardiol. 2005 Aug 16;46(4):688-9 [PMID: 16098436 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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