PMID- 19025427
OWN - NLM
STAT- MEDLINE
DCOM- 20090223
LR  - 20121115
IS  - 0277-0008 (Print)
IS  - 0277-0008 (Linking)
VI  - 28
IP  - 12
DP  - 2008 Dec
TI  - Pharmacokinetics of ibutilide in patients with heart failure due to left 
      ventricular systolic dysfunction.
PG  - 1461-70
LID - 10.1592/phco.28.12.1461 [doi]
AB  - 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.
FAU - Tisdale, James E
AU  - Tisdale JE
AD  - Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, 
      Purdue University, 1001 W 10th Street, Indianapolis, IN, USA. jtisdale@iupui.edu
FAU - Overholser, Brian R
AU  - Overholser BR
FAU - Sowinski, Kevin M
AU  - Sowinski KM
FAU - Wroblewski, Heather A
AU  - Wroblewski HA
FAU - Amankwa, Kwadwo
AU  - Amankwa K
FAU - Borzak, Steven
AU  - Borzak S
FAU - Kingery, Joanna R
AU  - Kingery JR
FAU - Coram, Rita
AU  - Coram R
FAU - Zipes, Douglas P
AU  - Zipes DP
FAU - Flockhart, David A
AU  - Flockhart DA
FAU - Kovacs, Richard J
AU  - Kovacs RJ
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pharmacotherapy
JT  - Pharmacotherapy
JID - 8111305
RN  - 0 (Anti-Arrhythmia Agents)
RN  - 0 (Sulfonamides)
RN  - 2436VX1U9B (ibutilide)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Anti-Arrhythmia Agents/adverse effects/blood/pharmacokinetics
MH  - Area Under Curve
MH  - Arrhythmias, Cardiac/chemically induced
MH  - Catheters, Indwelling
MH  - Electrocardiography/methods
MH  - Half-Life
MH  - Heart Failure/*drug therapy/metabolism/physiopathology
MH  - Heart Rate/drug effects
MH  - Humans
MH  - Infusions, Intravenous
MH  - Long QT Syndrome/chemically induced
MH  - Male
MH  - Middle Aged
MH  - Monte Carlo Method
MH  - Prospective Studies
MH  - Remission, Spontaneous
MH  - Severity of Illness Index
MH  - Sulfonamides/adverse effects/blood/*pharmacokinetics
MH  - Tachycardia/chemically induced
MH  - Time Factors
MH  - Ventricular Dysfunction, Left/*physiopathology
EDAT- 2008/11/26 09:00
MHDA- 2009/02/24 09:00
CRDT- 2008/11/26 09:00
PHST- 2008/11/26 09:00 [pubmed]
PHST- 2009/02/24 09:00 [medline]
PHST- 2008/11/26 09:00 [entrez]
AID - 10.1592/phco.28.12.1461 [pii]
AID - 10.1592/phco.28.12.1461 [doi]
PST - ppublish
SO  - Pharmacotherapy. 2008 Dec;28(12):1461-70. doi: 10.1592/phco.28.12.1461.