Role of Desethylamiodarone in the Anticoagulant Effect of Concurrent Amiodarone and Warfarin Therapy

Background: The concurrent use of amiodarone and warfarin inhibits metabolism of S-war-farin by cytochrome P450 (CYP) 2C9, thereby increasing the anticoagulant effect of war-farin. Amiodarone primarily inhibits CYP1A2 and CYP3A4, and desethylamiodarone primarily inhibits CYP2C9. We investigate whether a relationship exists between the plasma concentration of desethylamiodarone and anticoagulation when amiodarone is administered to patients receiving warfarin therapy.Methods and Results: The correlation between the plasma concentration of either amiodarone or desethylamiodarone, and prolongation of prothrombin time-international normalized ratio/dose of warfarin (A INR/Dose) on day 7 of amiodarone administration was studied in 25 patients (22-74 years old) with structural heart disease and refractory arrhythmias receiving stable warfarin therapy.Results: No correlation was found between the plasma concentration of amiodarone and A INR/Dose, but a correlation was found between the plasma concentration of de...