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Phenoconversion of Cytochrome P450 Metabolism: A Systematic Review
Phenoconversion is the mismatch between the individual’s genotype-based prediction of drug metabolism and the true capacity to metabolize drugs due to nongenetic factors. While the concept of phenoconversion has been described in narrative reviews, no systematic review is available. A systematic rev...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565093/ https://www.ncbi.nlm.nih.gov/pubmed/32906709 http://dx.doi.org/10.3390/jcm9092890 |
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author | Klomp, Sylvia D. Manson, Martijn L. Guchelaar, Henk-Jan Swen, Jesse J. |
author_facet | Klomp, Sylvia D. Manson, Martijn L. Guchelaar, Henk-Jan Swen, Jesse J. |
author_sort | Klomp, Sylvia D. |
collection | PubMed |
description | Phenoconversion is the mismatch between the individual’s genotype-based prediction of drug metabolism and the true capacity to metabolize drugs due to nongenetic factors. While the concept of phenoconversion has been described in narrative reviews, no systematic review is available. A systematic review was conducted to investigate factors contributing to phenoconversion and the impact on cytochrome P450 metabolism. Twenty-seven studies met the inclusion criteria and were incorporated in this review, of which 14 demonstrate phenoconversion for a specific genotype group. Phenoconversion into a lower metabolizer phenotype was reported for concomitant use of CYP450-inhibiting drugs, increasing age, cancer, and inflammation. Phenoconversion into a higher metabolizer phenotype was reported for concomitant use of CYP450 inducers and smoking. Moreover, alcohol, pregnancy, and vitamin D exposure are factors where study data suggested phenoconversion. The studies reported genotype–phenotype discrepancies, but the impact of phenoconversion on the effectiveness and toxicity in the clinical setting remains unclear. In conclusion, phenoconversion is caused by both extrinsic factors and patient- and disease-related factors. The mechanism(s) behind and the extent to which CYP450 metabolism is affected remain unexplored. If studied more comprehensively, accounting for phenoconversion may help to improve our ability to predict the individual CYP450 metabolism and personalize drug treatment. |
format | Online Article Text |
id | pubmed-7565093 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75650932020-10-26 Phenoconversion of Cytochrome P450 Metabolism: A Systematic Review Klomp, Sylvia D. Manson, Martijn L. Guchelaar, Henk-Jan Swen, Jesse J. J Clin Med Review Phenoconversion is the mismatch between the individual’s genotype-based prediction of drug metabolism and the true capacity to metabolize drugs due to nongenetic factors. While the concept of phenoconversion has been described in narrative reviews, no systematic review is available. A systematic review was conducted to investigate factors contributing to phenoconversion and the impact on cytochrome P450 metabolism. Twenty-seven studies met the inclusion criteria and were incorporated in this review, of which 14 demonstrate phenoconversion for a specific genotype group. Phenoconversion into a lower metabolizer phenotype was reported for concomitant use of CYP450-inhibiting drugs, increasing age, cancer, and inflammation. Phenoconversion into a higher metabolizer phenotype was reported for concomitant use of CYP450 inducers and smoking. Moreover, alcohol, pregnancy, and vitamin D exposure are factors where study data suggested phenoconversion. The studies reported genotype–phenotype discrepancies, but the impact of phenoconversion on the effectiveness and toxicity in the clinical setting remains unclear. In conclusion, phenoconversion is caused by both extrinsic factors and patient- and disease-related factors. The mechanism(s) behind and the extent to which CYP450 metabolism is affected remain unexplored. If studied more comprehensively, accounting for phenoconversion may help to improve our ability to predict the individual CYP450 metabolism and personalize drug treatment. MDPI 2020-09-07 /pmc/articles/PMC7565093/ /pubmed/32906709 http://dx.doi.org/10.3390/jcm9092890 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Klomp, Sylvia D. Manson, Martijn L. Guchelaar, Henk-Jan Swen, Jesse J. Phenoconversion of Cytochrome P450 Metabolism: A Systematic Review |
title | Phenoconversion of Cytochrome P450 Metabolism: A Systematic Review |
title_full | Phenoconversion of Cytochrome P450 Metabolism: A Systematic Review |
title_fullStr | Phenoconversion of Cytochrome P450 Metabolism: A Systematic Review |
title_full_unstemmed | Phenoconversion of Cytochrome P450 Metabolism: A Systematic Review |
title_short | Phenoconversion of Cytochrome P450 Metabolism: A Systematic Review |
title_sort | phenoconversion of cytochrome p450 metabolism: a systematic review |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565093/ https://www.ncbi.nlm.nih.gov/pubmed/32906709 http://dx.doi.org/10.3390/jcm9092890 |
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