Amiodarone pharmacokinetics in coronary patients: differences between acute and one-month chronic dosing

The pharmacokinetics of amiodarone (A) and its desethylamiodarone metabolite (DEA) were compared in the same coronary patients after a first 1000 mg dose and one-month chronic oral dosing. Terminal half-life (t1/2 el) of amiodarone increased from a mean (SD) 24.1 +/- 19.5 h after the first dose to 20.4 +/- 4.8 days after the last dose. Desethylamiodarone slowly appeared in the plasma after the first oral dose and its apparent t el was 61.6 +/- 26.6 h. After one-month dosing apparent t1/2 el of desethylamiodarone increased to 29.5 +/- 9.7 days. Mean maximal plasma amiodarone/desethylamiodarone concentration ratio decreased from 9.2 +/- 5.0 to 2.0 +/- 0.6 after chronic dosing. This change was mainly related to an increase in the plasma concentration of desethylamiodarone. These data suggest that after long-term treatment with amiodarone, the complete elimination of the drug and its metabolite may need 3-4 months in some patients. The results of this study were presented in part at the meeting of the Societe Francaise de Therapeutique et de Pharmacologie Clinique, Paris, December 1985.