Practice of CYP450 genotyping and phenotyping in children in a real-life setting
Pharmacokinetics varies widely between children. Many factors play an important role in this variability, such as ontogeny, pharmacogenetics, gender, comorbidities, and drug-drug interactions. Significant work has already been done in adults to understand the impact of genetic polymorphisms on drug-...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1130100/full |
| _version_ | 1811160261249204224 |
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| author | Frédérique Rodieux Youssef Daali Youssef Daali Youssef Daali Victoria Rollason Victoria Rollason Caroline F. Samer Caroline F. Samer Caroline F. Samer Kuntheavy Ing Lorenzini Kuntheavy Ing Lorenzini |
| author_facet | Frédérique Rodieux Youssef Daali Youssef Daali Youssef Daali Victoria Rollason Victoria Rollason Caroline F. Samer Caroline F. Samer Caroline F. Samer Kuntheavy Ing Lorenzini Kuntheavy Ing Lorenzini |
| author_sort | Frédérique Rodieux |
| collection | DOAJ |
| description | Pharmacokinetics varies widely between children. Many factors play an important role in this variability, such as ontogeny, pharmacogenetics, gender, comorbidities, and drug-drug interactions. Significant work has already been done in adults to understand the impact of genetic polymorphisms on drug-metabolizing enzyme activity and drug response. Data remain poor in children due to ontogeny that impacts genotyping-phenotyping correlation and the difficulty enrolling children in prospective studies. Our study aimed to describe the use of cytochromes P450 (CYP) phenotyping and/or genotyping tests in children in a real-life setting and assess the correlation between the genotype and the phenotype. We reviewed the results of tests performed between January 2005 and December 2020. Fifty-two children were genotyped and/or phenotyped. Four patients were excluded from the present analysis as they only underwent ABCB1 genotyping, without CYP testing. Of the remainder, 18 underwent simultaneous CYP genotyping and phenotyping, while 17 underwent CYP genotyping only, and 13 underwent CYP phenotyping only. In all cases, investigations were performed after the following situations: insufficient clinical response to treatment, low plasma concentrations, and adverse drug reactions (ADR). The vast majority of cases were related to immunosuppressive or antipsychotic therapy. Genotyping and/or phenotyping explained or contributed to the aforementioned clinical events in 56% of cases. The correlation between the genotype and the phenotype showed variability depending on the assessed cytochrome. In several cases, the phenotype did not correspond to the genotype because of comedications. In conclusion, there is clearly value in guiding drug based on CYP activity in children. |
| first_indexed | 2024-04-10T05:55:37Z |
| format | Article |
| id | doaj.art-e183021b6369401a9c1e799d36e8f7f2 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-10T05:55:37Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-e183021b6369401a9c1e799d36e8f7f22023-03-03T17:36:39ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-02-011410.3389/fphar.2023.11301001130100Practice of CYP450 genotyping and phenotyping in children in a real-life settingFrédérique Rodieux0Youssef Daali1Youssef Daali2Youssef Daali3Victoria Rollason4Victoria Rollason5Caroline F. Samer6Caroline F. Samer7Caroline F. Samer8Kuntheavy Ing Lorenzini9Kuntheavy Ing Lorenzini10Division of Clinical Pharmacology and Toxicology, Department of Anesthesiology, Pharmacology, Emergency Medicine and Intensive care, Geneva University Hospitals, Geneva, SwitzerlandDivision of Clinical Pharmacology and Toxicology, Department of Anesthesiology, Pharmacology, Emergency Medicine and Intensive care, Geneva University Hospitals, Geneva, SwitzerlandSchool of Pharmaceutical Sciences, University of Geneva, Geneva, SwitzerlandFaculty of Medicine, University of Geneva, Geneva, SwitzerlandDivision of Clinical Pharmacology and Toxicology, Department of Anesthesiology, Pharmacology, Emergency Medicine and Intensive care, Geneva University Hospitals, Geneva, SwitzerlandFaculty of Medicine, University of Geneva, Geneva, SwitzerlandDivision of Clinical Pharmacology and Toxicology, Department of Anesthesiology, Pharmacology, Emergency Medicine and Intensive care, Geneva University Hospitals, Geneva, SwitzerlandSchool of Pharmaceutical Sciences, University of Geneva, Geneva, SwitzerlandFaculty of Medicine, University of Geneva, Geneva, SwitzerlandDivision of Clinical Pharmacology and Toxicology, Department of Anesthesiology, Pharmacology, Emergency Medicine and Intensive care, Geneva University Hospitals, Geneva, SwitzerlandFaculty of Medicine, University of Geneva, Geneva, SwitzerlandPharmacokinetics varies widely between children. Many factors play an important role in this variability, such as ontogeny, pharmacogenetics, gender, comorbidities, and drug-drug interactions. Significant work has already been done in adults to understand the impact of genetic polymorphisms on drug-metabolizing enzyme activity and drug response. Data remain poor in children due to ontogeny that impacts genotyping-phenotyping correlation and the difficulty enrolling children in prospective studies. Our study aimed to describe the use of cytochromes P450 (CYP) phenotyping and/or genotyping tests in children in a real-life setting and assess the correlation between the genotype and the phenotype. We reviewed the results of tests performed between January 2005 and December 2020. Fifty-two children were genotyped and/or phenotyped. Four patients were excluded from the present analysis as they only underwent ABCB1 genotyping, without CYP testing. Of the remainder, 18 underwent simultaneous CYP genotyping and phenotyping, while 17 underwent CYP genotyping only, and 13 underwent CYP phenotyping only. In all cases, investigations were performed after the following situations: insufficient clinical response to treatment, low plasma concentrations, and adverse drug reactions (ADR). The vast majority of cases were related to immunosuppressive or antipsychotic therapy. Genotyping and/or phenotyping explained or contributed to the aforementioned clinical events in 56% of cases. The correlation between the genotype and the phenotype showed variability depending on the assessed cytochrome. In several cases, the phenotype did not correspond to the genotype because of comedications. In conclusion, there is clearly value in guiding drug based on CYP activity in children.https://www.frontiersin.org/articles/10.3389/fphar.2023.1130100/fullchildrenpharmacogeneticsgenotypingphenotypingCYP450 |
| spellingShingle | Frédérique Rodieux Youssef Daali Youssef Daali Youssef Daali Victoria Rollason Victoria Rollason Caroline F. Samer Caroline F. Samer Caroline F. Samer Kuntheavy Ing Lorenzini Kuntheavy Ing Lorenzini Practice of CYP450 genotyping and phenotyping in children in a real-life setting Frontiers in Pharmacology children pharmacogenetics genotyping phenotyping CYP450 |
| title | Practice of CYP450 genotyping and phenotyping in children in a real-life setting |
| title_full | Practice of CYP450 genotyping and phenotyping in children in a real-life setting |
| title_fullStr | Practice of CYP450 genotyping and phenotyping in children in a real-life setting |
| title_full_unstemmed | Practice of CYP450 genotyping and phenotyping in children in a real-life setting |
| title_short | Practice of CYP450 genotyping and phenotyping in children in a real-life setting |
| title_sort | practice of cyp450 genotyping and phenotyping in children in a real life setting |
| topic | children pharmacogenetics genotyping phenotyping CYP450 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1130100/full |
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