Pharmacokinetics of intravenous amiodarone and its electrocardiographic effects on healthy Japanese subjects

Heart Vessels. 2011 May;26(3):274-81. doi: 10.1007/s00380-010-0047-7. Epub 2010 Oct 30.

Abstract

The aim of this phase I, dose-escalating study was to evaluate the pharmacokinetics, electrocardiographic effect and safety of amiodarone after a single intravenous administration in Japanese subjects. Thirty-two healthy Japanese male volunteers (20-32 years) were randomized to three single-dose groups (1.25, 2.5 and 5.0 mg/kg). In each group, six (1.25 mg/kg) or ten (2.5 and 5.0 mg/kg) subjects received a single 15-min infusion of intravenous amiodarone, and two subjects received glucose solution as control. The pharmacokinetic profile, blood pressure and electrocardiographic analyses were obtained on a timely basis after up to 77 days. The maximum plasma concentration (C (max)) and area under the concentration-time curve (AUC(0-96)) for amiodarone 1.25, 2.5 and 5.0 mg/kg displayed dose-dependent characteristics: mean C (max) was 2,920 ± 610, 7,140 ± 1,480 and 13,660 ± 3,410 ng/ml, respectively; the mean AUC(0-96) was 3,600 ± 700, 8,100 ± 1,600 and 16,600 ± 4,300 ng h/ml, respectively. A long serum half-life (>14 days) was observed for amiodarone and desethylamiodarone. PR intervals were prolonged at 15 min (0.16 ± 0.0.1 vs. 0.15 ± 0.01 s, p = 0.03) and 18 min (0.17 ± 0.01 vs. 0.15 ± 0.01 s, p = 0.03) with the 5.0 mg/kg dose compared with baseline. No other significant changes in electrocardiographic parameters, pulse rate or blood pressure were observed. A needle-pain-induced vasovagal effect appeared in a volunteer, and three volunteers experienced pain at the drug infusion site. After a single infusion of amiodarone at doses of 1.25-5.0 mg/kg, serum concentrations increased in a dose-dependent manner. A single intravenous amiodarone dose barely affected the electrocardiographic parameters and was well tolerated.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amiodarone / administration & dosage*
  • Amiodarone / adverse effects
  • Amiodarone / analogs & derivatives
  • Amiodarone / blood
  • Amiodarone / pharmacokinetics*
  • Anti-Arrhythmia Agents / administration & dosage*
  • Anti-Arrhythmia Agents / adverse effects
  • Anti-Arrhythmia Agents / blood
  • Anti-Arrhythmia Agents / pharmacokinetics*
  • Area Under Curve
  • Asian People*
  • Biotransformation
  • Blood Pressure / drug effects*
  • Computer Simulation
  • Electrocardiography, Ambulatory*
  • Half-Life
  • Heart Rate / drug effects*
  • Humans
  • Infusions, Intravenous
  • Japan
  • Male
  • Models, Biological
  • Young Adult

Substances

  • Anti-Arrhythmia Agents
  • desethylamiodarone
  • Amiodarone