Ndesethylamiodarone

N-desethylamiodarone, abbreviated N-DEA, is the major active metabolite of the antiarrhythmic drug amiodarone. It is produced in the liver by N-desethylation of amiodarone, primarily by cytochrome P450 enzymes such as CYP3A4. The metabolite is highly lipophilic and distributes widely in tissues, contributing to the extensive tissue accumulation seen with amiodarone therapy.

Pharmacology: N-DEA retains substantial antiarrhythmic activity and appears to prolong cardiac repolarization similarly to amiodarone, thereby participating in the drug’s overall electrophysiologic effects, including QT interval prolongation. The metabolite may contribute to the same adverse effect profile as amiodarone, including thyroid dysfunction (due to iodine load), hepatic injury, pulmonary toxicity, and photosensitivity, particularly with long-term use.

Pharmacokinetics: N-DEA has a long elimination half-life, and plasma and tissue levels can remain elevated for weeks to months after cessation of amiodarone. It is excreted mainly in the bile, with some renal elimination. Interindividual variability is common, influenced by hepatic function and concomitant medications.

Clinical relevance: Because of its persistence and activity, N-DEA contributes to the prolonged pharmacologic and toxic effects of amiodarone therapy. Routine measurement of N-DEA is not standard practice, but drug exposure can be assessed in specialized settings or research. Drug interactions that affect CYP3A4 can alter N-DEA concentrations.