Home Bratislava Medical Journal 2013 Bratislava Medical Journal Vol.114, No.4, p.206–212, 2013

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Published Monthly, in English
Founded: 1919
ISSN 0006-9248
(E)ISSN 1336-0345

Impact factor 1.564


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Bratislava Medical Journal Vol.114, No.4, p.206–212, 2013

Title: Cytochrome P450 2D6 phenotype and genotype in hypertensive patients on long-term therapy with metoprolol
Author: J. Duricova, I. Perinova, N. Jurckova, I. Jeziskova, I. Kacirova, M. Grundmann

Abstract:  Objective: The aim was to compare cytochrome P450 2D6 phenotype and genotype using metoprolol as a probe drug. Further, to investigate the influence of P450 2D6 activity on metoprolol pharmacokinetics and pharmacodynamics in patients on metoprolol therapy.
Background: Cytochrome P450 2D6 is a highly polymorphic enzyme that contributes to the variability of metoprolol. However, environmental factors also modify drug disposition.
Methods: Forty-nine hypertensive patients were enrolled. Serum metoprolol and α-hydroxymetoprolol concentrations, resting heart rate were measured before, 1, 3 and 4 hours post-dose.
Results: Significantly higher normalized metoprolol serum concentrations, normalized metoprolol AUC0-4 and metoprolol oral clearance were observed in patients with lower P450 2D6 metabolic activity. A trend towards a lower resting heart rate before metoprolol intake was also observed in this group of patients. The differences in metoprolol disposition were more expressed when P450 2D6 phenotype instead of genotype was determined.
Conclusion: Significant variations exist in metoprolol disposition in hypertensive patients. Both genotyping and phenotyping provides a valuable method in determining the enzymatic activity and in optimising metoprolol therapy (Tab. 3, Fig. 8, Ref. 35).

Keywords: metoprolol, cytochrome P450 2D6, genotype, phenotype
Year: 2013, Volume: 114, Issue: 4 Page From: 206, Page To: 212

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