Clinical pharmacokinetics of amiodarone.

This article attempts to provide an overview of the present knowledge of the pharmacokinetics of amiodarone and how this relates to the clinical usage of oral amiodarone. It is apparent that wide gaps still exist in our knowledge of amiodarone's pharmacokinetics in humans and the best fit for the observations following a single oral dose and chronic dosing is that of a three compartment model with body tissues acting as a large reservoir of the drug; hence the very large volume of distribution (greater than 5001). It remains unclear as to exactly when steady state is achieved except that full clinical efficacy for ventricular tachyarrhythmias may take several weeks following high oral dosing (about 15g). The drug's bioavailability is modest (approximately 40%) and excretion is minimal via the hepatic route. It is extensively metabolised in all tissues to desethylamiodarone, whose antiarrhythmic properties remain to be elucidated. This metabolite is found to parallel amiodarone's concentration in serum but its concentration is variable in tissues. The liver shows the highest, and body fat the lowest concentrations of desethylamiodarone. The minimal effective serum concentration has not been established with certainty, and the unique pharmacokinetics of this agent has made it difficult to perform dose-response studies, especially in life threatening arrhythmias. Similarly, the toxic serum concentrations have not been established though it appears that a higher incidence of side effects occurs if serum concentrations exceed 2.5 mg/l during chronic (steady state) therapy.