title: Amiodarone concentration in human myocardium after rapid intravenous administration.
abstract: Intravenous amiodarone has been found useful in the emergent management of life-threatening arrhythmias. Experimental studies have shown that its electrophysiologic effects are proportional to its myocardial concentration. However, early after its intravenous administration, the extent of the concentration of amiodarone in the human myocardium, the site of its action, is not well known. This study was performed to measure the myocardial concentration of amiodarone shortly after rapid intravenous injection. Amiodarone, 150 mg, was injected over 15 seconds intravenously into 9 patients, 52 +/- 9 years of age, weighing between 65 and 98 kg (mean = 81 +/- 15.6). All patients suffered from idiopathic dilated cardiomyopathy, were in NYHA functional class II, and the mean left ventricular ejection fraction was 21 +/- 6%. Right ventricular endomyocardial biopsy, required for the establishment of the diagnosis, was performed 2-5 minutes after drug administration for measurements of its myocardial concentration. Plasma concentrations of amiodarone were also measured at 2, 5, 10, and 60 minutes, and measurements of right heart hemodynamics were made 2 and 10 minutes after the injection. At 2.5 +/- 1.2 minutes after amiodarone administration, the mean myocardial concentration was 95.7 +/- 67.4 micrograms/g (range, 16-175), and the myocardial/plasma amiodarone ratio was 5.05 +/- 5.01. Heart rate increased from 82 +/- 17 to 90 +/- 13 beats/min (P < 0.05), and systolic blood pressure decreased from 132 +/- 19 to 118 +/- 17 mmHg (P < 0.03). The extent of myocardial fibrosis was 5.13 +/- 6.55% (range, 0.3-17.5%). Intravenous amiodarone (150 mg) accumulates rapidly in the human myocardium. This pharmacokinetic characteristic probably explains its acute efficacy in the treatment of life-threatening arrhythmias.
authors.affiliation: University of Athens School of Medicine, Department of Clinical Therapeutics, Alexandra Hospital, Greece.
authors.forename: M I
authors.initials: MI
authors.lastname: Anastasiou-Nana
authors.forename: J N
authors.initials: JN
authors.lastname: Nanas
authors.forename: G
authors.initials: G
authors.lastname: Alexopoulos
authors.forename: J N
authors.initials: JN
authors.lastname: Karli
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Margari
authors.forename: E
authors.initials: E
authors.lastname: Agapitos
authors.forename: E N
authors.initials: EN
authors.lastname: Patsi
authors.forename: S F
authors.initials: SF
authors.lastname: Stamatelopoulos
mesh_terms: D000328:Adult; D000368:Aged; D000638:Amiodarone / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D001835:Body Weight / Q000502:physiology; D002311:Cardiomyopathy, Dilated / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005355:Fibrosis; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D000889:Anti-Arrhythmia Agents; D014665:Vasodilator Agents; D000638:Amiodarone