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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
I. Kacirova, M. Lazarova, R. Urinovska, J. Dodulik, J. Vaclavik
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články
- MeSH
- antagonisté beta-1-adrenergních receptorů * aplikace a dávkování MeSH
- cytochrom P-450 CYP2D6 metabolismus MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- metoprolol * aplikace a dávkování farmakokinetika analogy a deriváty farmakologie MeSH
- natriuretický peptid typu B * krev MeSH
- peptidové fragmenty krev MeSH
- pilotní projekty MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- srdeční selhání * farmakoterapie patofyziologie MeSH
- tepový objem * účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
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].
Department of Clinical Pharmacology Faculty of Medicine University of Ostrava Ostrava Czech Republic
Department of Internal Medicine and Cardiology University Hospital Ostrava Ostrava Czech Republic
Department of Internal Medicine Faculty of Medicine University of Ostrava Ostrava Czech Republic
Citace poskytuje Crossref.org
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- $a Kacirova, Ivana $u Department of Clinical Pharmacology, Institute of Laboratory Medicine, University Hospital Ostrava, Ostrava, Czech Republic $u Department of Clinical Pharmacology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
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- $a 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 / $c I. Kacirova, M. Lazarova, R. Urinovska, J. Dodulik, J. Vaclavik
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- $a 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].
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