Amiodarone has pharmacokinetic interactions with a number of therapeutic drugs, including warfarin, phenytoin, flecainide, and cyclosporine. Metoprolol is mainly metabolized by CYP2D6, and desethylamiodarone, a metabolite of amiodarone, has a markedly greater inhibitory effect on CYP2D6 than amiodarone. Therefore, the goal of this study was to evaluate the effect of amiodarone and desethylamiodarone on the serum concentration/dose ratio (C/D) of metoprolol in 120 inpatients with cardiac arrhythmias that received either metoprolol and amiodarone (MET+AMD group, n=30) or metoprolol alone (MET group, n=90). The ratio of administered metoprolol was compared between the MET and the MET+AMD groups. The dose of metoprolol and patient age were significantly higher in the MET group when compared with the MET+AMD group (1.00+/-0.480 versus 0.767+/-0.418 mg/kg/day, p<0.050; 68.6+/-10.6 versus 57.6+/-14.1 years, p<0.001, respectively), but the C/D ratio was significantly lower in the MET group than in the MET+AMD group (90.8+/-64.0 versus 136+/-97.8, p<0.01). Furthermore, a significant correlation was found between the C/D ratio and desethylamiodarone concentration (n=30, r=0.371, p<0.01). The results suggest that there is a significant interaction between amiodarone and metoprolol via desethylamiodarone-induced inhibition of CYP2D6. Therefore, careful monitoring of metoprolol concentrations/bioactivity of CYP2D6 is required in the context of co-administration of amiodarone and metoprolol.