Interaction of amiodarone with racemic warfarin and its separated enantiomorphs in humans

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Abstract
To evaluate a stereoselective interaction for amiodarone and racemic warfarin, we performed a prospective study with its separated enantiomorphs. Single oral doses of racemic warfarin, 1.5 mg/kg, were administered to six normal subjects, with and without oral amidarone, 400 mg daily, for the hypoprothrombinemic duration. Both the hypoprothrombinemia (P < 0.001) and plasma warfarin concentrations (P < 0.01) were significantly increased. The experiments were repeated separately with the R- and S-warfarin enantiomorphs. S-warfarin with amiodarone significantly increased both the hypoprothrombinemia (P < 0.001) and plasma warfarin concentrations (P < 0.01). R-warfarin with amiodarone significantly increased both the hypoprothrombinemia (P < 0.001) and plasma warfarin concentrations (P < 0.001). Thus amiodarone augmented the anticoagulant effect nonstereoselectively by reduced metabolic clearance of both warfarin enantiomorphs. Amiodarone and racemic warfarin can be a dangerous combination, particularly when either drug is added to a stabilized regimen of the other drug, unless the prothrombin times are monitored carefully.

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