Key result
Amiodarone co-administration is linked to a ~143% higher metoprolol concentration-to-dose ratio and decreased clearance.
Why the study?
Metoprolol is metabolized via CYP2D6, which is weakly inhibited by amiodarone and desethylamiodarone, prompting evaluation of the drug interaction between them.
Does amiodarone co-administration alter the serum concentration and apparent clearance of metoprolol in patients with atrial fibrillation?
Observational (n=41)
No
Does amiodarone co-administration alter the serum concentration and apparent clearance of metoprolol in patients with atrial fibrillation?
Amiodarone significantly inhibits metoprolol metabolism, leading to higher concentration-to-dose ratios and lower clearance, necessitating therapeutic drug monitoring when these drugs are co-administered.
Answers are grounded in this paper and cite their sources.
Co-administration was associated with higher metoprolol exposure; extends interaction evidence but leaves open monitoring or outcome impact.
Background Metoprolol is a cardioselective beta-1 adrenergic receptor blocker, for which about 70–80% of metabolism occurs via the cytochrome P450 2D6 enzyme. Amiodarone and its active metabolite desethylamiodarone are weak inhibitors of cytochrome P450 2D6. Methods In this study, the drug interaction between metoprolol and amiodarone was objectified by determining the serum concentrations of both drugs including their metabolites. Results Patients with concentrations of amiodarone and/or desethylamiodarone ≥ 0.5 mg/L achieved a significantly higher concentration-to-dose ratio and lower weight-adjusted apparent clearance of metoprolol than patients who were not taking amiodarone. A significant correlation was found between the concentration of metoprolol and its dose and concentrations of both amiodarone and desethylamiodarone. The concentration-to-dose ratio and the apparent clearance index of metoprolol correlated with the concentrations of metoprolol, amiodarone, and desethylamiodarone. Lower heart rate was found at concentrations of metoprolol ≥ 12.0 µg/L and/or amiodarone or desethylamiodarone ≥ 0.5 mg/L compared to drug concentrations measured below these values. Conclusion Due to the variability of concentrations achieved after administration of the same daily dose of metoprolol and amiodarone, it is advisable to monitor amiodarone and desethylamiodarone concentrations and, if necessary, metoprolol concentrations in patients taking this combination.
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Kolek et al. (2026) conducted an observational in Atrial fibrillation (n=41). Amiodarone co-administration vs. Metoprolol without amiodarone was evaluated on Metoprolol concentration-to-dose (c/D) ratio (p=<0.001). Concomitant use of amiodarone significantly increased the metoprolol concentration-to-dose ratio (median 0.34 vs 0.14) and decreased its apparent clearance index (p<0.001).
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