| Pharmacokinetics of ibutilide in patients with heart failure due to left ventricular systolic dysfunction. | |
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MedLine Citation:
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PMID: 19025427 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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STUDY OBJECTIVE: To assess whether the increased risk of ibutilide-induced torsade de pointes in patients with heart failure may be due to increased ibutilide exposure, we sought to determine if the pharmacokinetics of ibutilide are altered in patients with heart failure due to left ventricular systolic dysfunction. DESIGN: Multicenter, prospective pharmacokinetic study. SETTING: Four academic medical centers in the United States. PATIENTS: Sixteen adult patients with atrial fibrillation or atrial flutter requiring conversion to normal sinus rhythm: six patients who had New York Heart Association (NYHA) class II or III heart failure due to left ventricular dysfunction (mean +/- SD left ventricular ejection fraction [LVEF] 30 +/- 9%); 10 patients who did not have left ventricular dysfunction (mean +/- SD LVEF 54 +/- 5% in six of these 10 patients) served as controls. INTERVENTION: All patients received a single dose of ibutilide 1.0 mg administered intravenously over 10 minutes. Blood samples were obtained through an indwelling catheter in the contralateral arm before ibutilide administration, at the end of the infusion, and at 5, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, and 48 hours after the infusion. MEASUREMENTS AND MAIN RESULTS: Serum ibutilide concentrations were determined by using high-performance liquid chromatography and mass spectrometry. No significant differences were noted between the heart failure and normal left ventricular function groups in the following parameters: maximum serum ibutilide concentration (median [interquartile range] 3.8 [2.3-5.7] vs 5.8 [3.1-14.4] microg/L, p=0.31), area under the serum concentration-time curve from time zero extrapolated to infinity (mean +/- SD 11.0 +/- 9.4 vs 13.2 +/- 10.6 microg*hr/L, p=0.88), steady-state volume of distribution (1380 +/- 334 vs 1390 +/- 964 L, p=0.99), systemic clearance (129 +/- 60 vs 125 +/- 81 L/hr, p=0.92), or half-life (12.5 +/- 10.7 vs 12.4 +/- 8.6 hrs, p=0.99). CONCLUSION: The pharmacokinetics of ibutilide do not appear to be altered in patients with NYHA class II or III heart failure due to left ventricular systolic dysfunction. Therefore, the increased risk of ibutilide-induced torsade de pointes in patients with heart failure does not appear to be due to increased ibutilide exposure. |
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Authors:
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James E Tisdale; Brian R Overholser; Kevin M Sowinski; Heather A Wroblewski; Kwadwo Amankwa; Steven Borzak; Joanna R Kingery; Rita Coram; Douglas P Zipes; David A Flockhart; Richard J Kovacs |
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Publication Detail:
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Type: Clinical Trial; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Pharmacotherapy Volume: 28 ISSN: 0277-0008 ISO Abbreviation: Pharmacotherapy Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-11-25 Completed Date: 2009-02-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8111305 Medline TA: Pharmacotherapy Country: United States |
Other Details:
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Languages: eng Pagination: 1461-70 Citation Subset: IM |
Affiliation:
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Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Purdue University, 1001 W 10th Street, Indianapolis, IN, USA. jtisdale@iupui.edu |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Anti-Arrhythmia Agents / adverse effects, blood, pharmacokinetics Area Under Curve Arrhythmias, Cardiac / chemically induced Catheters, Indwelling Electrocardiography / methods Half-Life Heart Failure / drug therapy*, metabolism, physiopathology Heart Rate / drug effects Humans Infusions, Intravenous Long QT Syndrome / chemically induced Male Middle Aged Monte Carlo Method Prospective Studies Remission, Spontaneous Severity of Illness Index Sulfonamides / adverse effects, blood, pharmacokinetics* Tachycardia / chemically induced Time Factors Ventricular Dysfunction, Left / physiopathology* |
| Chemical | |
Reg. No./Substance:
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0/Anti-Arrhythmia Agents; 0/Sulfonamides; 130350-52-6/ibutilide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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