CYP450 Genotype-Phenotype Concordance Using the Geneva Micrococktail in a Clinical Setting

Article Article scientifique Article CYP450 Genotype-Phenotype Concordance Using the Geneva Micrococktail in a Clinical Setting eng 2021-08-26 2021 author Ing Lorenzini Kuntheavy 0000-0001-8472-7714 510277 author Desmeules Jules Alexandre 73542 author Rollason Victoria 40955 author Bertin Stéphane 835262 author Besson Marie 87576 author Daali Youssef 46042 author Samer Caroline Flora 0000-0001-8178-0616 105661 730637 10.3389/fphar.2021.730637 34512355 1663-9812 PMC8427306 https://www.frontiersin.org/articles/10.3389/fphar.2021.730637/full Pharmacokinetic variability is a major source of differences in drug response and can be due to genetic variants and/or drug-drug interactions. Cytochromes P450 are among the most studied enzymes from a pharmacokinetic point of view. Their activity can be measured by phenotyping, and/or predicted by genotyping. Depending on the presence of drugs and/or diseases that can affect their in vivo activity, both approaches can be complementary. In 2014, the Geneva cocktail using dried blood spots was validated in healthy volunteers for CYP450 phenotyping. Since its clinical implementation, it has been used in approximately 500 patients in various clinical situations. Our study aims to report the concordance between CYP450 genotype and phenotype in real-life patients. The prospectively collected data from patients who were genotyped and/or phenotyped between January 2014 and December 2020 were reviewed. A total of 537 patients were genotyped and/or phenotyped for CYP450 during this period, and 241 underwent simultaneous genotyping and phenotyping allowing for genotype/phenotype concordance assessment. Genotyping correctly predicted poor metabolizer phenotypes for most CYPs isoenzymes studied, whereas agreement was more variable for intermediate, normal, and ultrarapid metabolizers. Discrepancies between the phenotype predicted on the basis of genotyping and the measured phenotype were not always explained by concurrent medication (phenotypic switch). Therefore genotyping and phenotyping tests are complementary approaches when aiming to individualize drug therapy. In the 537 patients, the majority of clinical situations were observed with analgesic/anesthetic drugs (n = 187), followed by antidepressants (n = 153), antineoplastics (n = 97), and immunosuppressants (n = 93). Inefficacy (or low drug levels) and adverse drug reaction (or high drug levels) were the main reasons for testing. Genotype and/or phenotype results explained or at least contributed to the clinical event in 44% of cases. Adverse drug reaction Cytochromes P450 Drug-drug interaction Genotype Inefficacy Phenoconversion Phenotype Dewey 617 63 Département d'anesthésiologie, pharmacologie, soins intensifs et urgences 229 false 1280 Pharmaco-omiques et médecine de précision 1003 302 Groupe Desmeules Jules (pharmacologie/toxicologie) 567 Frontiers in pharmacology 12 93e795f2-9b11-4d48-bd65-8dd8c0704605 Article (Published version) Public Article-scientifique-from-europePmc.pdf 1135298 application/pdf CC BY-4.0 openAccess Faculté de médecine / Section de médecine clinique / Département d'anesthésiologie, pharmacologie, soins intensifs et urgences

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CYP450 Genotype-Phenotype Concordance Using the Geneva Micrococktail in a Clinical Setting	Frontiers in pharmacology			2021	288	401

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Bertin, Stéphane