PMID: 11907638Mar 22, 2002Paper

Role of desethylamiodarone in the anticoagulant effect of concurrent amiodarone and warfarin therapy

Journal of Cardiovascular Pharmacology and Therapeutics
M NaganumaE Fujii

Abstract

The concurrent use of amiodarone and warfarin inhibits metabolism of S-warfarinby cytochrome P450 (CYP) 2C9, thereby increasing the anticoagulant effect of warfarin. 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. The correlation between the plasma concentration of either amiodarone or desethylamiodarone, and prolongation of prothrombin time-international normalized ratio/dose of warfarin (Delta 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. No correlation was found between the plasma concentration of amiodarone and Delta INR/Dose, but a correlation was found between the plasma concentration of desethylamiodarone and Delta INR/Dose. 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.

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Citations

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Jul 12, 2005·Current Treatment Options in Cardiovascular Medicine·Edith A Nutescu, Cathy M Helgason
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Jan 13, 2005·Canadian Journal of Physiology and Pharmacology·Arwen L HunterDavid J Granville
Mar 2, 2006·The Annals of Pharmacotherapy·Mesbah RahmanEric G Butchart
Jul 13, 2012·The Cochrane Database of Systematic Reviews·Han WangJue Lin Deng
Jul 19, 2006·Canadian Journal of Physiology and Pharmacology·Manreet K Chehal, David J Granville
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