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European Journal of Clinical Pharmacology

, Volume 70, Issue 6, pp 695–699 | Cite as

Risperidone metabolic ratio as a biomarker of individual CYP2D6 genotype in schizophrenic patients

  • Buster MannheimerEmail author
  • Johan Holm
  • Larissa Koukel
  • Leif Bertilsson
  • Urban Ösby
  • Erik Eliasson
Pharmacogenetics

Abstract

Purpose

The purpose of the present study was to investigate the predictive value of the risperidone metabolic ratio for the individual CYP2D6 genotype.

Methods

The determination of risperidone, 9-hydroxyrisperidone, and CYP2D6 genotype was performed in 89 schizophrenic patients. The receiver operator characteristic (ROC) method and the area under the ROC curve (AUC) were used to illustrate the predictive value of risperidone metabolic ratio for the individual CYP2D6 genotype. The area under the ROC curve (AUC) was used as a global measure of this predictive value. To evaluate the proposed cutoff levels of >1 and <0.1 to identify individuals with a poor or ultrarapid CYP2D6 genotype the sensitivity, specificity, positive predictive value and negative predictive were calculated.

Results

The area under the ROC curve (AUC) for poor and ultrarapid metabolisers was 0.85 and 0.86, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of a risperidone/9–OH-risperidone ratio >1 to CYP2D6 poor metaboliser genotype were 75 %, 95 %, 60 % and 97 %, respectively. The corresponding measures for a metabolic ratio < 0.1 to predict ultrarapid metabolisers were 80 %, 77 %, 18 % and 98 %.

Conclusions

A metabolic ratio > 1 or < 0.1 may be a useful therapeutic biomarker to recommend CYP2D6 genetic testing to guide the present or future treatment of patients in need of psychotropic drugs.

Keywords

CYP2D6 genotype Genetic polymorphism Therapeutic drug monitoring Psychotropic drugs 

Notes

Acknowledgements

The work was supported financially by the Swedish Society for Medical Research, Stockholm County Council and Karolinska Institutet. We wish to thank Dr Jonatan Lindh for valuable input on data presentation and comments on the manuscript.

Declaration of potential conflicts of interest

The authors declare no conflicts of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Buster Mannheimer
    • 1
    Email author
  • Johan Holm
    • 2
  • Larissa Koukel
    • 2
  • Leif Bertilsson
    • 2
  • Urban Ösby
    • 3
    • 4
  • Erik Eliasson
    • 2
  1. 1.Karolinska Institutet, Department of Clinical Science and Education at SödersjukhusetStockholmSweden
  2. 2.Department of Laboratory Medicine, Division of Clinical PharmacologyKarolinska University Hospital HuddingeStockholmSweden
  3. 3.Department of Molecular Medicine and SurgeryNeurogenetics Unit, and Centre for Molecular MedicineStockholmSweden
  4. 4.Department of PsychiatryTiohundra ABNorrtäljeSweden

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