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Enantiospecific pharmacokinetics of metoprolol in CYP2D6 ultra-rapid metabolizers and correlation with exercise-induced heart rate

  • Pharmacogenetics
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Abstract

Objective

Our objective was to study the enantioselective pharmacokinetics of metoprolol in CYP2D6 ultra-rapid metabolizers (UM) compared with extensive (EM) and poor (PM) metabolizers to quantify differential effects of metoprolol enantiomers on the beta1-adrenoreceptor blockade.

Methods

Twenty-nine healthy individuals were selected based on their CYP2D6 genotype, and 100 mg racemic metoprolol was administered. Plasma concentrations of R- and S-metoprolol and the metabolites SS-, SR-, RS-, and RR-hydroxymetoprolol were quantified by high-performance liquid chromatography.

Results

Mean (±SD) AUCs of S-metoprolol were 190 ± 99 ng/ml·h in UMs, 366 ± 158 in EMs, and 1,804 ± 300 in PMs. For R-metoprolol, the AUCs were 127 ± 72 ng/ml·h in UMs, 261 ± 126 in EMs, and 1,746 ± 319 in PMs. The concentrations of R-metoprolol and S-metoprolol, respectively, needed to obtain a half-maximum reduction in heart rate were estimated as 20 and 21 ng/ml in PMs, 11 and 17 ng/ml in EMs, and 7 and 11 ng/ml in UMs.

Conclusion

A slight enantiopreference towards metabolism of R-metoprolol by CYP2D6 was observed in EMs and even more in the UM group, but the effect was far from being enantioselective.

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Authors and Affiliations

  1. Institute of Pharmacology of Natural Products & Clinical Pharmacology, University of Ulm, Helmholtzstr. 20, 89081, Ulm, Germany

    Angela Seeringer & Julia Kirchheiner

  2. Department of Clinical Pharmacology, Georg August University, Göttingen, Germany

    Jürgen Brockmöller

  3. Institute of Clinical Pharmacology, Charité University of Medicine, Berlin, Germany

    Steffen Bauer

Authors
  1. Angela Seeringer
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  2. Jürgen Brockmöller
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  3. Steffen Bauer
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  4. Julia Kirchheiner
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Correspondence to Angela Seeringer.

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Seeringer, A., Brockmöller, J., Bauer, S. et al. Enantiospecific pharmacokinetics of metoprolol in CYP2D6 ultra-rapid metabolizers and correlation with exercise-induced heart rate. Eur J Clin Pharmacol 64, 883–888 (2008). https://doi.org/10.1007/s00228-008-0504-8

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  • DOI: https://doi.org/10.1007/s00228-008-0504-8

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