Pharmacokinetics of intravenous amiodarone in patients with impaired left ventricular function.
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 < or = 45%; n = 6), or severely impaired (ejection fraction < or = 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 (t1/2) of DEA, statistical comparisons revealed no significant between-group differences in pharmacokinetic parameters or correlations between pharmacokinetic parameters and ejection fractions. The t1/2 of DEA was increased by approximately 60% in patients with severe left ventricular dysfunction 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.
Vadiei
K
K
Department of Clinical Pharmacology, Clinical Research and Development, Wyeth-Ayerst Research, Radnor, PA 19087, USA.
O'Rangers
E A
EA
Klamerus
K J
KJ
Kluger
J
J
Kazierad
D J
DJ
Leese
P T
PT
Chow
M S
MS
Zimmerman
J J
JJ
D000328:Adult; D000368:Aged; D000638:Amiodarone / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D005260:Female; D006207:Half-Life; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D016277:Ventricular Function, Left
D000889:Anti-Arrhythmia Agents; D000638:Amiodarone