BACKGROUND: Pharmacokinetics and tissue concentrations of amiodarone may vary considerably in end-stage heart failure, but may be crucial for treatment efficiency and antiarrhythmic drug therapy. OBJECTIVE: This study was undertaken to determine plasma amiodarone and desethylamiodarone concentrations and to determine whether they correlate with myocardial concentrations in explanted hearts from patients with end-stage heart failure. PATIENTS AND METHODS: Eight patients with idiopathic dilated cardiomyopathy and normal coronary arteries were included in the present study. Myocardial tissue samples (seven sites) and epicardial fat were taken from each explanted heart, and drug concentrations of amiodarone and desethylamiodarone were determined. In addition, plasma drug levels were measured and compared with the myocardial amiodarone/desethylamiodarone concentrations. RESULTS: The mean cumulative amiodarone dose was 91 g and the mean plasma concentrations of amiodarone and desethylamiodarone were 0.68 and 0.84 microg.ml(-1), respectively. The tissue concentrations of amiodarone amounted to 13.2 and 28.3 microg.g(-1), respectively, in the atria and to 13.0 and 40.8 microg.g(-1), respectively, in the ventricles. The distribution of the drug and its metabolite were similar in the right and left ventricles. There was a good correlation between myocardial concentration of amiodarone and desethylamiodarone and the cumulative ingested dose of amiodarone. Tissue drug concentrations correlated only poorly with plasma amiodarone or desethylamiodarone levels. The highest drug levels were measured in the epicardial fat tissue, where the ratio of amiodarone 105 microg.g(-1) to desethylamiodarone 32 microg.g(-1) was reversed (3.3 compared with 0.29 in the ventricles). Thus, amiodarone concentrations in epicardial fat were approximately 10 times higher than myocardial and 150 times higher than plasma levels. CONCLUSIONS: Our data confirm the slow equilibrium of amiodarone and desethylamiodarone concentrations between plasma and myocardium. Myocardial tissue concentrations of desethylamiodarone and, to a lesser degree, amiodarone correlate with the cumulative ingested dose of amiodarone. Monitoring of the total cumulative dose may be more relevant clinically than monitoring plasma levels. These results support the clinical practice of reducing the maintenance dose of amiodarone in patients who are on long-term treatment.
BACKGROUND: Pharmacokinetics and tissue concentrations of amiodarone may vary considerably in end-stage heart failure, but may be crucial for treatment efficiency and antiarrhythmic drug therapy. OBJECTIVE: This study was undertaken to determine plasma amiodarone and desethylamiodarone concentrations and to determine whether they correlate with myocardial concentrations in explanted hearts from patients with end-stage heart failure. PATIENTS AND METHODS: Eight patients with idiopathic dilated cardiomyopathy and normal coronary arteries were included in the present study. Myocardial tissue samples (seven sites) and epicardial fat were taken from each explanted heart, and drug concentrations of amiodarone and desethylamiodarone were determined. In addition, plasma drug levels were measured and compared with the myocardial amiodarone/desethylamiodarone concentrations. RESULTS: The mean cumulative amiodarone dose was 91 g and the mean plasma concentrations of amiodarone and desethylamiodarone were 0.68 and 0.84 microg.ml(-1), respectively. The tissue concentrations of amiodarone amounted to 13.2 and 28.3 microg.g(-1), respectively, in the atria and to 13.0 and 40.8 microg.g(-1), respectively, in the ventricles. The distribution of the drug and its metabolite were similar in the right and left ventricles. There was a good correlation between myocardial concentration of amiodarone and desethylamiodarone and the cumulative ingested dose of amiodarone. Tissue drug concentrations correlated only poorly with plasma amiodarone or desethylamiodarone levels. The highest drug levels were measured in the epicardial fat tissue, where the ratio of amiodarone 105 microg.g(-1) to desethylamiodarone 32 microg.g(-1) was reversed (3.3 compared with 0.29 in the ventricles). Thus, amiodarone concentrations in epicardial fat were approximately 10 times higher than myocardial and 150 times higher than plasma levels. CONCLUSIONS: Our data confirm the slow equilibrium of amiodarone and desethylamiodarone concentrations between plasma and myocardium. Myocardial tissue concentrations of desethylamiodarone and, to a lesser degree, amiodarone correlate with the cumulative ingested dose of amiodarone. Monitoring of the total cumulative dose may be more relevant clinically than monitoring plasma levels. These results support the clinical practice of reducing the maintenance dose of amiodarone in patients who are on long-term treatment.
Authors: Daniela Husser; Karl-Heinz Binias; Martin Stridh; Leif Sornmo; S Bertil Olsson; Jochen Molling; Christoph Geller; Helmut U Klein; Andreas Bollmann Journal: Ann Noninvasive Electrocardiol Date: 2005-04 Impact factor: 1.468
Authors: Jose R Garcia; Peter F Campbell; Gautam Kumar; Jonathan J Langberg; Liliana Cesar; Juline N Deppen; Eric Y Shin; Neal K Bhatia; Lanfang Wang; Kai Xu; Frank Schneider; Brian Robinson; Andrés J García; Rebecca D Levit Journal: Circ Arrhythm Electrophysiol Date: 2018-05