JOURNAL OF THE CZECH PHARMACEUTICAL SOCIETY AND THE SLOVAK PHARMACEUTICAL SOCIETY

Čes. slov. farm. 2010, 59(5):222-226

Comparison of metoprolol/α-hydroxymetoprolol metabolic ratio after a single dose and in steady state

J. Ďuricová*, I. Peřinová, I. Kacířová, M. Grundmann
Department of Clinical Pharmacology, University Hospital Ostrava, and Faculty of Medicine, University of Ostrava, Czech Republic

Metoprolol/α-hydroxymetoprolol metabolic ratio (MR) 3 hours after a single metoprolol dose is used for cytochrome P450 2D6 phenotyping. The aim was to compare cytochrome P450 2D6 metabolic activity after the first metoprolol dose and in steady state. Thirteen adult hypertensive patients (7 females) in whom an introduction of the beta-blocker metoprolol was indicated were included. Age (mean ± SD) was 42.8 ± 12.9 years, weight (mean ± SD) was 94.0 ± 25.4 kg. Metoprolol dose was chosen based on clinical grounds on the day of metoprolol first ingestion. Blood samples were drawn after the first dose and at least 2 weeks since metoprolol introduction to ensure steady state. The patients were phenotyped as extensive metabolizers in both periods, after metoprolol first ingestion and in steady state. We observed a significant correlation (rs = 0.8418, P = 0.0003) between the metoprolol/α-hydroxymetoprolol MRs. All the patients were phenotyped as extensive metabolizers in both periods, despite statistically significant differences between the median MRs (0.59 versus 0.81, P = 0.0266). The differences were not of such an extent so as to assign subjects to different phenotypic groups. Metoprolol/α-hydroxymetoprolol MR in steady state is an appropriate alternative to metoprolol/α-hydroxymetoprolol MR after a single dose.

Keywords: cytochrome P450 2D6; phenotype; probe drug; metoprolol

Received: August 27, 2010; Accepted: October 5, 2010; Published: May 1, 2010  Show citation

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Ďuricová J, Peřinová I, Kacířová I, Grundmann M. Comparison of metoprolol/α-hydroxymetoprolol metabolic ratio after a single dose and in steady state. Čes. slov. farm. 2010;59(5):222-226.
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