Amiodarone Elimination Half-Life
The elimination half-life of amiodarone is highly variable and unusually long, averaging approximately 58 days (range 15-100 days), with this prolonged elimination resulting from slow release of the drug from lipid-rich tissues where it accumulates extensively. 1
Pharmacokinetic Characteristics
The extraordinarily long half-life of amiodarone is one of its most clinically significant pharmacokinetic properties:
- The terminal elimination half-life averages 55-58 days after chronic oral therapy, though individual variability is substantial 1, 2
- After single-dose administration, the reported half-life ranges from 3.2 to 79.7 hours, but this does not reflect the true elimination kinetics seen with chronic dosing 3
- Following withdrawal of long-term amiodarone treatment, the half-life extends to approximately 100 days in some patients 3
- Population pharmacokinetic modeling confirms a terminal half-life of 55 days with a rapid distribution half-life of 17 hours 2
Clinical Implications of the Long Half-Life
The prolonged elimination creates several important clinical considerations:
- After reaching steady state, cessation of dosing produces only a 25% decrease in serum concentration after 3 days and a 50% decrease after 36 days 2
- The antiarrhythmic protection may persist for varying intervals, up to 150 days or more, after the drug has been discontinued 4
- Maximal therapeutic effects (as well as the most significant adverse effects) are not attained before 90 to 150 days of treatment due to the prolonged time to steady state 4
- The slow elimination rate makes anticipating the timing of adjustments in amiodarone therapy to avoid toxicity unusually perplexing 2
Mechanism of Prolonged Elimination
The extended half-life results from specific pharmacokinetic properties:
- Amiodarone is highly lipophilic and accumulates extensively in adipose tissue, skeletal muscle, liver, lungs, and skin 1
- The drug has an exceptionally large volume of distribution (12,700 L for the peripheral compartment) 2
- The long half-life is thought to result from the drug's slow release from lipid-rich tissue stores 1
- Tissue/plasma partition coefficients are exceptionally high, contributing to the prolonged elimination 5
Comparison with Active Metabolite
The major metabolite desethylamiodarone (DEA) also has antiarrhythmic properties, though its contribution to overall effect is not well established 1. The parent drug's pharmacokinetics dominate clinical decision-making regarding dosing and discontinuation.