What is the half-life of amiodarone?

Half-Life of Amiodarone

The elimination half-life of amiodarone averages approximately 58 days (range 55-58 days) after chronic oral therapy, though this is highly variable between individuals. 1, 2

Pharmacokinetic Profile

Terminal Elimination Half-Life

• After chronic oral administration, the terminal elimination half-life averages 55-58 days, with substantial individual variability reported in the literature. 1, 2
• Following single-dose intravenous administration, the initial half-life is much shorter (5-20 hours), but this does not reflect the true elimination kinetics. 3
• After discontinuation of long-term therapy, terminal half-lives ranging from 14-58 days have been documented, with some reports extending to 15-100 days depending on duration of therapy and individual patient factors. 4, 3

Distribution Phase

• The distribution half-life (t½ alpha) out of the central compartment to peripheral and deep tissue compartments is much shorter, approximately 4 hours. 5
• After intravenous bolus administration, serum concentrations decline to 10% of peak values within 30-45 minutes due to rapid tissue distribution. 6

Mechanism of Prolonged Elimination

The unusually long half-life results from amiodarone's extreme lipophilicity and slow release from lipid-rich tissue stores. 1, 2

• Amiodarone accumulates extensively in adipose tissue, skeletal muscle, liver, lungs, and skin due to exceptionally high tissue-to-plasma partition coefficients. 2, 5
• The drug has a massive volume of distribution, which contributes to its prolonged elimination kinetics. 5, 7
• Elimination occurs primarily through hepatic metabolism and biliary excretion, with negligible renal excretion. 6

Active Metabolite Considerations

• The major metabolite desethylamiodarone (DEA) also has antiarrhythmic properties and accumulates with prolonged therapy to reach concentrations approximately equal to amiodarone itself. 1
• DEA serum concentrations above 0.05 mg/L typically do not appear until after several days of continuous infusion. 6
• The terminal elimination half-life of DEA is also prolonged and may be even longer in patients with severe left ventricular dysfunction. 6

Clinical Implications

Onset and Offset of Effects

• Due to the 58-day average half-life, there is a significant pretherapeutic latency period before maximal effects are achieved, typically requiring 90-150 days of treatment. 4
• Antiarrhythmic protection and adverse effects may persist for up to 150 days or more after discontinuation. 4
• This prolonged elimination means that drug interactions and toxicities can continue long after stopping the medication. 1, 8

Age-Related Differences

• Elderly patients (>65 years) show lower clearances (approximately 100 mL/h/kg) compared to younger subjects (approximately 150 mL/h/kg), with half-life increasing from about 20 days to 47 days. 6

Disease State Effects

• Renal impairment does not significantly influence amiodarone pharmacokinetics. 6
• Hepatic cirrhosis affects DEA levels but not amiodarone concentrations. 6
• Severe left ventricular dysfunction prolongs the terminal disposition half-life of DEA but does not significantly alter amiodarone pharmacokinetics. 6