Amiodarone and its desethyl metabolite: tissue distribution and morphologic changes during long-term therapy

Area of Science:

• Pharmacology
• Cell Biology
• Toxicology

Background:

• Amiodarone is known for its complex pharmacokinetic profile.
• Previous studies suggested extensive tissue deposition of amiodarone.

Purpose of the Study:

• To quantify amiodarone and its metabolite desethylamiodarone concentrations in various human tissues.
• To investigate the ultrastructural changes associated with amiodarone deposition.

Main Methods:

• Measurement of amiodarone and desethylamiodarone in autopsy, surgical, and biopsy tissue samples from 18 patients.
• Analysis of tissue concentrations using wet weight measurements.
• Electron microscopy and energy-dispersive X-ray microanalysis to identify ultrastructural changes and elemental composition.

Main Results:

• High concentrations of amiodarone and desethylamiodarone were found in fat, liver, lung, adrenal gland, testis, and lymph nodes.
• Significantly higher drug concentrations were observed in pigmented skin compared to unpigmented skin.
• Lysosomal inclusion bodies containing iodine were identified in dermal macrophages and other cell types, indicative of lipidosis.

Conclusions:

• Amiodarone therapy leads to widespread tissue deposition of the drug and its metabolite.
• This deposition causes ultrastructural changes consistent with lipidosis in various organs.
• The findings correlate with observed adverse effects of amiodarone, particularly in the skin, liver, and lung.