BACKGROUND: The cardioselective β-1 receptor antagonist metoprolol is used to treat heart failure. It is metabolized in the liver, primarily by cytochrome 2D6. RESEARCH DESIGN AND METHODS: In this study, trough serum concentrations of metoprolol and its metabolite α-hydroxymetoprolol were measured in patients with heart failure with reduced ejection fraction. RESULTS: Concentrations were 1.3-122.9 µg/L for metoprolol and 1.3-125.7 µg/L for α-hydroxymetoprolol, metabolic ratios were 0.11-98.32. The median weight-adjusted apparent clearance of metoprolol was 53.07 (range 3.24-500.0). Metoprolol and α-hydroxymetoprolol concentrations correlated with both daily dose and dose per kilogram of body weight. However, metoprolol concentrations at the same daily dose showed a wide variability. Patients taking 100 mg/day had significantly lower NT-proBNP values than those taking 25 or 50 mg/day. Patients with LVEF ≤ 35% versus >
35% used significantly lower daily doses and doses per kilogram of body weight, although metoprolol concentrations did not differ. A poor cytochrome 2D6 metabolizer phenotype was detected in two patients. CONCLUSIONS: Metoprolol concentrations showed a wide interindividual variability at the same daily dose. Simultaneous determination of metoprolol and α-hydroxymetoprolol concentrations could identify patients at risk of possible accumulation of metoprolol leading to intoxication or, conversely, patients at risk of underdosing. [Figure: see text].