Absolute bioavailability of amiodarone in normal subjects

Area of Science:

• Pharmacokinetics
• Drug Metabolism
• Clinical Pharmacology

Background:

• Amiodarone is an antiarrhythmic drug with variable oral absorption.
• Understanding the bioavailability of different oral formulations is crucial for therapeutic efficacy.

Purpose of the Study:

• To compare the relative and absolute bioavailability of various oral amiodarone formulations.
• To investigate the absorption characteristics and potential first-pass effect of oral amiodarone.

Main Methods:

• A crossover study involving 12 subjects.
• Administration of intravenous amiodarone and three oral formulations (commercial tablets, new tablets, drinkable solution).
• Plasma amiodarone and metabolite levels measured by High-Performance Liquid Chromatography (HPLC).

Main Results:

• All oral amiodarone formulations demonstrated bioequivalence for kinetic parameters.
• Mean oral bioavailability was determined to be 65% ± 22%.
• Peak plasma levels were reached approximately 4.5 hours post-administration.

Conclusions:

• The commercial and new tablet formulations are bioequivalent to the drinkable solution.
• Incomplete oral absorption of amiodarone is likely due to a first-pass metabolic effect rather than dissolution issues.
• Further research into first-pass metabolism is warranted for amiodarone therapy.