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-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.


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.
Naganuma
M
M
Department of Pharmacy, The Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, Japan.
Shiga
T
T
Nishikata
K
K
Tsuchiya
T
T
Kasanuki
H
H
Fujii
E
E
D000328:Adult; D000368:Aged; D000638:Amiodarone / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D000925:Anticoagulants / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006331:Heart Diseases / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D014859:Warfarin / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use
D000925:Anticoagulants; D014859:Warfarin; C036116:desethylamiodarone; D000638:Amiodarone