The mechanism of the interaction between amiodarone and warfarin in humans.
Article Details
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Heimark LD, Wienkers L, Kunze K, Gibaldi M, Eddy AC, Trager WF, O'Reilly RA, Goulart DA
The mechanism of the interaction between amiodarone and warfarin in humans.
Clin Pharmacol Ther. 1992 Apr;51(4):398-407.
- PubMed ID
- 1563209 [ View in PubMed]
- Abstract
Amiodarone decreased the total body clearance of both (R)- and (S)-warfarin in normal subjects but did not change volumes of distribution. Warfarin excretion products were quantified and clearance and formation clearance values calculated. Amiodarone and metabolites inhibited the reduction of (R)-warfarin to (R,S)-warfarin alcohol-1 and the oxidation of both (R)- and (S)-warfarin to phenolic metabolites. Inhibition of warfarin hydroxylation by amiodarone in human liver microsomes was compared with the in vivo results. In agreement, the in vitro data indicates that amiodarone is a general inhibitor of the cytochrome P450 catalyzed oxidation of both enantiomers of warfarin, but the metabolism of (S)-warfarin is more strongly inhibited than that of (R)-warfarin. These data suggest that the enhanced anticoagulant effect observed when amiodarone and warfarin are coadministered is attributable to inhibition of P4502C9, the isozyme of P-450 primarily responsible for the conversion of (S)-warfarin to its major metabolite, (S)-7-hydroxywarfarin.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Amiodarone Cytochrome P450 2C9 Protein Humans UnknownInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAcenocoumarolAmiodarone The risk or severity of bleeding can be increased when Amiodarone is combined with Acenocoumarol. WarfarinAmiodarone The risk or severity of bleeding can be increased when Amiodarone is combined with Warfarin.