Amiodarone

Absorption	Slow and variable (about 20 to 55% of an oral dose is absorbed).
Volume of distribution	Not Available
Protein binding	>96%
Metabolism	Amiodarone is extensively metabolized in the liver via CYP2C8 (under 1% unchanged in urine), and can effect the metabolism of numerous other drugs. The major metabolite of amiodarone is desethylamiodarone (DEA), which also has antiarrhythmic properties. The metabolism of amiodarone is inhibited by grapefruit juice, leading to elevated serum levels of amiodarone. Enzyme Metabolite Reaction Km Vmax Cytochrome P450 2D6 N-desethylamiodarone N-deethylation Cytochrome P450 1A2 N-desethylamiodarone N-deethylation Cytochrome P450 3A4 N-desethylamiodarone N-deethylation 54.2 329.58 Cytochrome P450 2C9 N-desethylamiodarone N-deethylation Cytochrome P450 2C8 N-desethylamiodarone N-deethylation 8.6 41.18
Route of elimination	Amiodarone is eliminated primarily by hepatic metabolism and biliary excretion and there is negligible excretion of amiodarone or DEA in urine.
Half life	58 days (range 15-142 days)
Clearance	90-158 mL/h/kg [Healthy with a single dose IV (5 mg/kg over 15 min)] 100 mL/h/kg [Normal subjects > 65 yrs] 150 mL/h/kg [younger subjects] 220 and 440 mL/h/kg [patients with VT and VF]
Toxicity	Intravenous, mouse: LD50 = 178 mg/kg. Some side effects have a significant mortality rate: specifically, hepatitis, exacerbation of asthma and congestive failure, and pneumonitis.
Affected organisms	Humans and other mammals
Pathways	Not Available