The Relevance of Integrating CYP2C19 Phenoconversion Effects into Clinical Pharmacogenetics.

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. 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 (PC 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. 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.

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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/).

Déclaration de conflit d'intérêts

J. Deckert was a co-recipient of a grant of the Bavarian Ministry of Economic Affairs, Regional Development and Energy (BayMED, MED-1604–0010) and an investigator in a European grant (Horizon 2020 SME program of the European Union ref 696802) to P1Vital. J. Deckert and H. Weber receive funding from the Deutschen Zentrum für Luft- und Raumfahrt (DLR) - Förderkennzeichen 01EK2204G (P4D, Project SP1, SP5A and Coordination). M. Scherf-Clavel, and S. Unterecker have no conflicts of interest. A. Reif has no conflicts of interest with relevance to the present work. M. Hahn, A. Eckert and A. Frantz have no conflicts of interest.