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Pharmacokinetics of Intravenous Amiodarone in Patients with Impaired Left Ventricular Function
Author(s) -
Vadiei Kiumars,
O'Rangers Eleanor A.,
Klamerus Karen J.,
Kluger Jeffrey,
Kazierad David J.,
Leese Philip T.,
Chow Moses S.,
Zimmerman James J.
Publication year - 1996
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1996.tb04241.x
Subject(s) - amiodarone , medicine , pharmacokinetics , ejection fraction , cardiology , active metabolite , anesthesia , heart failure , atrial fibrillation
To evaluate the potential need for modification of dose regimens of intravenous amiodarone in patients with left ventricular dysfunction, the pharmacokinetics of amiodarone and its active metabolite, desethylamiodarone (DEA), were examined after a single 15‐minute intravenous infusion of amiodarone 5 mg/kg. Three parallel groups of otherwise healthy volunteers with normal (n = 12), moderately impaired (ejection fraction > 30 but ≤ 45%; n = 6), or severely impaired (ejection fraction ≤ 30%; n = 6) left ventricular function were enrolled in the study. Serial blood samples were obtained over a 76‐day period for estimation of pharmacokinetic parameters. With the exception of the half‐life (t 1/2 ) of DEA, statistical comparisons revealed no significant between‐group differences in pharmacokinetic parameters or correlations between pharmacokinetic parameters and ejection fractions. The t 1/2 of DEA was increased by approximately 60% in patients with severe left ventricular dysunction compared with that in patients with moderately impaired and normal left ventricular function. The rate of DEA formation is slow, however, and its concentration relative to amiodarone is low. Therefore, it is unlikely that concentrations of DEA in serum would reach levels that contribute significantly to the pharmacologic activity of amiodarone during short‐term (up to 2 weeks) intravenous amiodarone therapy. Single doses of amiodarone were well tolerated. The results of this study suggest that intravenous amiodarone can be used with appropriate observation to control arrhythmias, regardless of the degree of left ventricular dysfunction .