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Serum concentrations of sertraline and N-desmethyl sertraline in relation to CYP2C19 genotype in psychiatric patients

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

To investigate the impact of CYP2C19 genotype on serum concentrations of sertraline and N-desmethyl sertraline in psychiatric patients.

Methods

Patients treated with sertraline (n = 121) were divided into six subgroups according to CYP2C19 genotype: CYP2C19*17/*17, CYP2C19*1/*17, CYP2C19*1/*1, CYP2C19*17/def, CYP2C19*1/def and CYP2C19def/def (def = allele encoding defective CYP2C19 metabolism, i.e. *2 and *3). Dose-adjusted serum concentrations were compared by linear mixed model analyses using the CYP2C19*1/*1 subgroup as reference.

Results

Subgroups carrying one or two alleles encoding defective CYP2C19 metabolism achieved significantly higher mean dose-adjusted serum concentrations of sertraline and N-desmethyl sertraline compared to the CYP2C19*1/*1 subgroup (P < 0.05). The effect of CYP2C19 genotype was expressed as 3.2-fold (sertraline) and 4.5-fold (N-desmethyl sertraline) higher dose-adjusted serum concentrations in the CYP2C19def/def subgroup compared to the CYP2C19*1/*1 subgroup (P < 0.01). The CYP2C19*17 allele had no influence on the dose-adjusted serum concentrations of sertraline and N-desmethyl sertraline.

Conclusion

The significantly higher serum concentrations associated with alleles encoding defective CYP2C19 metabolism might be of relevance for the clinical outcome of sertraline treatment.

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Acknowledgements

The authors thank Marianne Hjerpset, Lene Kristin Støten and Linda Uthus for performing the serum analyses and the genotyping.

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Authors and Affiliations

  1. Department of Psychopharmacology, Diakonhjemmet Hospital, P.O. Box 85 Vinderen, N-0319, Oslo, Norway

    I. Rudberg, M. Hermann, H. Refsum & E. Molden

  2. Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway

    E. Molden

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  1. I. Rudberg
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  2. M. Hermann
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  3. H. Refsum
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  4. E. Molden
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Correspondence to I. Rudberg.

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Rudberg, I., Hermann, M., Refsum, H. et al. Serum concentrations of sertraline and N-desmethyl sertraline in relation to CYP2C19 genotype in psychiatric patients. Eur J Clin Pharmacol 64, 1181–1188 (2008). https://doi.org/10.1007/s00228-008-0533-3

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  • DOI: https://doi.org/10.1007/s00228-008-0533-3

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