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Review

Phenoconversion of Cytochrome P450 Metabolism: A Systematic Review

1
Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
2
Leiden Network for Personalised Therapeutics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
3
Division of BioTherapeutics, Leiden Academic Centre for Drug Research (LACDR), Leiden University, 2333 CC Leiden, The Netherlands
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(9), 2890; https://doi.org/10.3390/jcm9092890
Received: 3 August 2020 / Revised: 3 September 2020 / Accepted: 4 September 2020 / Published: 7 September 2020
(This article belongs to the Special Issue Advances and Challenges in Pharmacogenomics)
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. View Full-Text
Keywords: phenoconversion; pharmacogenetics; cytochrome P450; concomitant medication; comorbidities; CYP2D6; CYP2C19; CYP3A5; personalized medicine phenoconversion; pharmacogenetics; cytochrome P450; concomitant medication; comorbidities; CYP2D6; CYP2C19; CYP3A5; personalized medicine
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MDPI and ACS Style

Klomp, S.D.; Manson, M.L.; Guchelaar, H.-J.; Swen, J.J. Phenoconversion of Cytochrome P450 Metabolism: A Systematic Review. J. Clin. Med. 2020, 9, 2890. https://doi.org/10.3390/jcm9092890

AMA Style

Klomp SD, Manson ML, Guchelaar H-J, Swen JJ. Phenoconversion of Cytochrome P450 Metabolism: A Systematic Review. Journal of Clinical Medicine. 2020; 9(9):2890. https://doi.org/10.3390/jcm9092890

Chicago/Turabian Style

Klomp, Sylvia D., Martijn L. Manson, Henk-Jan Guchelaar, and Jesse J. Swen 2020. "Phenoconversion of Cytochrome P450 Metabolism: A Systematic Review" Journal of Clinical Medicine 9, no. 9: 2890. https://doi.org/10.3390/jcm9092890

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