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

Department of Pharmacy, The Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, Japan

Tsuyoshi Shiga, MD, PhD

Department of Cardiology, The Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, Japan

Kaori Nishikata, BS

Takanori Tsuchiya, MS

Department of Pharmacy, The Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, Japan

Hiroshi Kasanuki, MD, PhD

Department of Cardiology, The Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, Japan

Emiko Fujii, PhD

Department of Pharmacy, The Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, Japan

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 desethylamiodarone and A INRIDose.

Conclusions: It was suggested that inhibition of CYP2C9 by desethylamiodarone, the active metabolite of amiodarone, plays an important role in the interaction of warfarin and amiodarone.

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 6, No. 4, 363-367 (2001)
DOI: 10.1177/107424840100600405


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