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CC BY-NC-ND 4.0 · Pharmacopsychiatry 2024; 57(02): 69-77
DOI: 10.1055/a-2248-6924
Original Paper

The Relevance of Integrating CYP2C19 Phenoconversion Effects into Clinical Pharmacogenetics

Maike Scherf-Clavel
1   Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, 97080 Würzburg, Germany
,
Heike Weber
1   Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, 97080 Würzburg, Germany
2   Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, 60528 Frankfurt, Germany
,
Stefan Unterecker
1   Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, 97080 Würzburg, Germany
,
Amelie Frantz
2   Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, 60528 Frankfurt, Germany
,
Andreas Eckert
2   Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, 60528 Frankfurt, Germany
,
Andreas Reif
2   Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, 60528 Frankfurt, Germany
,
Jürgen Deckert
1   Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, 97080 Würzburg, Germany
,
Martina Hahn
2   Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, 60528 Frankfurt, Germany
3   Department of Mental Health, Varisano Hospital Frankfurt Hoechst, 65929 Frankfurt, Germany
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Abstract

Introduction CYP2D6 and CYP2C19 functional status as defined by genotype is modulated by phenoconversion (PC) due to pharmacokinetic interactions. As of today, there is no data on the effect size of PC for CYP2C19 functional status. The primary aim of this study was to investigate the impact of PC on CYP2C19 functional status.

Methods Two patient cohorts (total n=316; 44.2±15.4 years) were investigated for the functional enzyme status of CYP2C19 applying two different correction methods (PCBousman, PCHahn&Roll) as well as serum concentration and metabolite-to-parent ratio of venlafaxine, amitriptyline, mirtazapine, sertraline, escitalopram, risperidone, and quetiapine.

Results There was a decrease in the number of normal metabolizers of CYP2C19 and an increase in the number of poor metabolizers. When controlled for age, sex, and, in the case of amitriptyline, venlafaxine, and risperidone, CYP2D6 functional enzyme status, an association was observed between the CYP2C19 phenotype/functional enzyme status and serum concentration of amitriptyline, sertraline, and escitalopram.

Discussion PC of CYP2C19 changes phenotypes but does not improve correlations with serum concentrations. However, only a limited number of patients received perturbators of CYP2C19. Studies with large numbers of patients are still lacking, and thus, it cannot be decided if there are minor differences and which method of correction to use. For the time being, PC is relevant in individual patients treated with CYP2C19-affecting drugs, for example, esomeprazole. To ensure adequate serum concentrations in these patients, this study suggests the use of therapeutic drug monitoring.

Keywords

pharmacogenetics - phenoconversion - pharmacokinetics - antidepressants - antipsychotics

Supplementary Material



Publication History

Received: 11 September 2023
Received: 09 November 2023

Accepted: 25 December 2023

Article published online:
14 February 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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