Analysis of serum concentrations of metoprolol and its metabolite α-hydroxymetoprolol in patients with heart failure with reduced ejection fraction: a pilot study in routine health care.
Ivana Kacirova, Marie Lazarova, Romana Urinovska, Jozef Dodulik, Jan Vaclavik
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Abstract
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.
期刊介绍：
Advances in drug development technologies are yielding innovative new therapies, from potentially lifesaving medicines to lifestyle products. In recent years, however, the cost of developing new drugs has soared, and concerns over drug resistance and pharmacoeconomics have come to the fore. Adverse reactions experienced at the clinical trial level serve as a constant reminder of the importance of rigorous safety and toxicity testing. Furthermore the advent of pharmacogenomics and ‘individualized’ approaches to therapy will demand a fresh approach to drug evaluation and healthcare delivery.
Clinical Pharmacology provides an essential role in integrating the expertise of all of the specialists and players who are active in meeting such challenges in modern biomedical practice.
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