Role of desethylamiodarone in the anticoagulant effect of concurrent amiodarone and warfarin therapy.
Article Details
- CitationCopy to clipboard
Naganuma M, Shiga T, Nishikata K, Tsuchiya T, Kasanuki H, Fujii E
Role of desethylamiodarone in the anticoagulant effect of concurrent amiodarone and warfarin therapy.
J Cardiovasc Pharmacol Ther. 2001 Oct;6(4):363-7. doi: 10.1177/107424840100600405.
- PubMed ID
- 11907638 [ View in PubMed]
- Abstract
BACKGROUND: 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. 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 (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. RESULTS: 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. 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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Amiodarone Cytochrome P450 1A2 Protein Humans UnknownInhibitorDetails Amiodarone Cytochrome P450 2C9 Protein Humans UnknownInhibitorDetails