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Semi-quantitative CYP2D6 gene doses in relation to metabolic ratios of psychotropics

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

Abstract

Purpose

Genetic polymorphisms in cytochrome P450 (CYP) enzyme CYP2D6 have a substantial effect on the success of pharmacotherapy. Different models, including a predicted-phenotype model and a semi-quantitative gene dose (SGD) model, have been developed based on CYP genotype. The objective of this study was to investigate the surplus value of the SGD model in predicting the metabolic ratios (MRs) of the psychotropics venlafaxine, fluoxetine and risperidone.

Methods

Phenotype prediction and semi-quantitative gene doses were conducted after genotyping for CYP2D6 *3, *4, *5, *6, *9, *10, *41 and gene multiplication.

Results

The predicted-phenotype and SGD model showed increasing mean MRs with increasing predicted metabolic activity and decreasing SGD values, respectively, for all three psychotropics. The reliability of MR prediction was higher for the SGD model.

Conclusions

Both models are suitable for venlafaxine, fluoxetine and risperidone. In this study, a surplus value of semi-quantitative gene dose model was present, but small, for all three psychotropics.

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Acknowledgements

The authors thank Erica van Baalen-Benedek, Windy Smallegoor, Chris Welker and Elsbeth Bannink, St Jansdal Hospital, for their help with obtaining the genetic and metabolic data.

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Authors and Affiliations

  1. Department of Clinical Chemistry, St Jansdal Hospital, P.O. Box 138, 3840 AC, Harderwijk, The Netherlands

    John W. J. Hinrichs, Harriët M. Loovers, Bart Scholten & Jan van der Weide

  2. Psychiatric Hospital Meerkanten, Ermelo, The Netherlands

    John W. J. Hinrichs, Harriët M. Loovers & Jan van der Weide

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  1. John W. J. Hinrichs
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  2. Harriët M. Loovers
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  3. Bart Scholten
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  4. Jan van der Weide
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Correspondence to Jan van der Weide.

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Hinrichs, J.W.J., Loovers, H.M., Scholten, B. et al. Semi-quantitative CYP2D6 gene doses in relation to metabolic ratios of psychotropics. Eur J Clin Pharmacol 64, 979–986 (2008). https://doi.org/10.1007/s00228-008-0509-3

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  • DOI: https://doi.org/10.1007/s00228-008-0509-3

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