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The Relevance of Integrating CYP2C19 Phenoconversion Effects into Clinical Pharmacogenetics
Maike Scherf-Clavel1, Heike Weber1,2, Stefan Unterecker1
1Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, 97080 Würzburg, Germany.
Pharmacopsychiatry
|February 14, 2024
Summary
Phenoconversion impacts CYP2C19 functional status, altering metabolizer phenotypes but not improving drug concentration correlations. Therapeutic drug monitoring is recommended for patients on CYP2C19-affecting medications.
Area of Science:
- Pharmacogenomics
- Drug Metabolism
- Clinical Pharmacology
Background:
- Cytochrome P450 enzymes, specifically CYP2D6 and CYP2C19, have their functional status influenced by phenoconversion (PC) due to drug interactions.
- Phenoconversion's effect on CYP2C19 functional status lacks quantitative data, necessitating this study to investigate its impact.
Purpose of the Study:
- To investigate the impact of phenoconversion (PC) on CYP2C19 functional status.
- To assess the effect size of PC on CYP2C19 phenotypes.
Main Methods:
- Investigated two patient cohorts (n=316) for CYP2C19 functional enzyme status using two correction methods (PC Bousman, PC Hahn&Roll).
- Analyzed serum concentrations and metabolite-to-parent ratios of several drugs, including venlafaxine, amitriptyline, sertraline, and escitalopram.
Main Results:
- Phenoconversion led to a shift in CYP2C19 metabolizer phenotypes, increasing poor metabolizers and decreasing normal metabolizers.
- Observed associations between CYP2C19 phenotype and serum concentrations of amitriptyline, sertraline, and escitalopram, after controlling for covariates.
Conclusions:
- Phenoconversion alters CYP2C19 phenotypes but did not enhance correlations with drug serum concentrations in this study.
- Further studies with larger patient numbers are needed to determine the clinical utility of PC correction methods.
- Therapeutic drug monitoring is suggested for patients on CYP2C19-affecting drugs to ensure adequate serum concentrations.
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