Amiodarone metabolic pathway

The Amiodarone metabolic pathway refers to the complex biotransformation of amiodarone, a Class III anti-arrhythmic agent used to treat life-threatening ventricular arrhythmias. This pathway primarily occurs in the liver and involves the N-deethylation of amiodarone into its major active metabolite, N-desethylamiodarone (DEA), a process mediated by the cytochrome P450 enzymes CYP3A4 and CYP2C8 [Source: PubMed, PMID: 11583450]. The pathway is clinically critical due to the drug's exceptionally long elimination half-life (averaging 58 days) and its tendency to accumulate in various tissues [Source: StatPearls, NBK482154]. Amiodarone and its metabolites are known to inhibit several other metabolic pathways, leading to a high risk of significant drug-drug interactions with medications like warfarin and digoxin [Source: NIH, LiverTox]. Furthermore, the metabolic breakdown of amiodarone releases inorganic iodine, which can disrupt thyroid function, while the accumulation of metabolites is linked to serious adverse effects such as pulmonary fibrosis and hepatotoxicity [Source: PubChem, CID 2157].

Other names

Amiodarone metabolismN-deethylation of amiodaroneCYP3A4-mediated amiodarone metabolism

Amiodarone is primarily metabolized by the enzymes CYP3A4 and CYP2C8 to its active metabolite, N-desethylamiodarone (DEA). Both the parent drug and its metabolite act as potent inhibitors of multiple cytochrome P450 enzymes (including CYP1A2, CYP2C9, CYP2D6, and CYP3A4) and the P-glycoprotein transporter, which significantly alters the clearance of co-administered medications.