European Journal of Clinical Pharmacology

, 64:1181

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

Pharmacogenetics

DOI: 10.1007/s00228-008-0533-3

Cite this article as:
Rudberg, I., Hermann, M., Refsum, H. et al. Eur J Clin Pharmacol (2008) 64: 1181. doi:10.1007/s00228-008-0533-3

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.

Keywords

CYP2C19CYP2C19*17GenotypeSertralineN-desmethyl sertraline

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Department of PsychopharmacologyDiakonhjemmet HospitalOsloNorway
  2. 2.Department of Pharmaceutical Biosciences, School of PharmacyUniversity of OsloOsloNorway