Pharmacokinetic Interaction Between Digoxin and Amiodarone

Abstract

Digoxin and amiodarone (AM) are used in therapy of atrial fibrillation. Amiodarone and its active metabolite desethylamiodarone (DEA) inhibit P-glycoprotein system and increase serum levels of digoxin with the risk of intoxication. Trough levels of digoxin (MEIA method) and AM including DEA (HPLC method) were analyzed in 322 patients in years 2007-2015 and analyzed retrospectively. Patients were divided in 4 groups according to AM levels and sum of AM+DEA levels (<0.5 mg/L, 0.5-1.0 mg/L, 1.0-2.0 mgl/L, >2.0 mg/L), in 3 groups according to DEA levels (<0.5 mg/L, 0.5-1.0 mg/L, >1 mg/L) and in 4 groups according to DEA/AM ratio (<0.5, 0.5-1.0, 1.0-1.5, >1.5). Control group consists of 2792 patients treated by digoxin itself. We observed relationship between concentration/dose (C/D) ratio of digoxin and concentration of AM, DEA, their ratio and summation. Statistically significant decrease of normalized daily dose of digoxin were observed in groups of patients with AM levels from 1.0 to 2.0 mg/L (about 21%) and >2.0 mg/L (about 15 %), with DEA levels from 0.5 to 1.0 mg/L (about 9%) and >1 mg/L (about 39%), with DEA/AM ratio from 0.5 to 1.0 (about 11.5%) and with sum of AM+DEA >2.0 mg/L (about 23%). We determined statistically significant correlation between C/D ratio of digoxin and AM concentration, DEA concentration and sum of AM+DEA. Any statistically significant correlation was not observed between C/D ratio of digoxin and DEA/AM ratio. We demonstrated that lower dose of digoxin is needed to reach the same level if the concetrations of AM (>1.0 mg/L), DEA (>0.5 mg/L) and their summation (>2.0 mg/L) is growing. Therapeutic drug monitoring of both drugs including DEA is an adequate method for dosage optimalization if the combination of digoxin and amiodarone is administered.