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CYP2D6 genotype and its relationship with metoprolol dose, concentrations and effect in patients with systolic heart failure

The Pharmacogenomics Journal volume 9, pages 175–184 (2009)Cite this article

Abstract

The aims of this study were to examine the relationships between CYP2D6 genotype and metoprolol dose, S- and R-metoprolol concentrations and clinical effects in patients with systolic heart failure. Data were obtained for 52 subjects, of which 27 had 2 functional alleles (24/27, CYP2D6*1/*1), 22 had 1 functional allele (18/22, CYP2D6*1/*4) and 3 had no functional alleles (CYP2D6*4/*4). Median dose-adjusted concentrations of S-metoprolol (active) were 6.3- and 3.2-fold higher in subjects with zero or one functional allele (P=0.016 and P=0.006), respectively, compared with subjects with two functional alleles. For the R-enantiomer (inactive), these concentrations were 10.7- and 3.7-fold higher (P=0.013 and P=0.003), respectively. Despite clear gene-concentration differences, no relationships between CYP2D6 genotype and dose or clinical effects could be shown. Although the number with no functional alleles was too small (n=3) to show effects, in patients with 1 functional allele other sources of variance are likely to be obscuring differences in clinical effects.

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Acknowledgements

We thank the New Zealand Pharmacy Education and Research Foundation and the Jim and Mary Carney Charitable Trust for financial support of this study. BPJ is the recipient of a research fellowship from the Danish Medical Research Council (Department of Science, Innovation and Technology, Denmark; FSS no. 271-06-0698). RLR is the recipient of Sir Charles Hercus Research Fellowship (Health Research Council of New Zealand).

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Authors and Affiliations

  1. Department of Pharmacy, Christchurch Hospital, Christchurch, New Zealand

    C F Sharp

  2. Department of Medicine, Clinical Pharmacology Research Group, University of Otago, Christchurch, New Zealand

    S J Gardiner, B P Jensen & E J Begg

  3. Department of Pathology, University of Otago, Christchurch, New Zealand

    R L Roberts

  4. Department of Cardiology, Christchurch Hospital, Christchurch, New Zealand

    R W Troughton & J G Lainchbury

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  1. C F Sharp
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  2. S J Gardiner
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Correspondence to E J Begg.

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Sharp, C., Gardiner, S., Jensen, B. et al. CYP2D6 genotype and its relationship with metoprolol dose, concentrations and effect in patients with systolic heart failure. Pharmacogenomics J 9, 175–184 (2009). https://doi.org/10.1038/tpj.2009.9

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