Metabolomics reveals biomarkers in human urine and plasma to predict cytochrome P450 2D6 (CYP2D6) activity.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_8116E84FC609
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Metabolomics reveals biomarkers in human urine and plasma to predict cytochrome P450 2D6 (CYP2D6) activity.
Journal
British journal of pharmacology
Author(s)
Magliocco G., Desmeules J., Matthey A., Quirós-Guerrero L.M., Bararpour N., Joye T., Marcourt L., Queiroz E.F., Wolfender J.L., Gloor Y., Thomas A., Daali Y.
ISSN
1476-5381 (Electronic)
ISSN-L
0007-1188
Publication state
Published
Issued date
12/2021
Peer-reviewed
Oui
Volume
178
Number
23
Pages
4708-4725
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Individualized assessment of cytochrome P450 2D6 (CYP2D6) activity is usually performed through phenotyping following administration of a probe drug to measure the enzyme's activity. To avoid any iatrogenic harm (allergic drug reaction, dosing error) related to the probe drug, the development of non-burdensome tools for real-time phenotyping of CYP2D6 could significantly contribute to precision medicine. This study focuses on the identification of markers of the CYP2D6 enzyme in human biofluids using an LC-high-resolution mass spectrometry-based metabolomic approach.
Plasma and urine samples from healthy volunteers were analysed before and after intake of a daily dose of paroxetine 20 mg over 7 days. CYP2D6 genotyping and phenotyping, using single oral dose of dextromethorphan 5 mg, were also performed in all participants.
We report four metabolites of solanidine and two unknown compounds as possible novel CYP2D6 markers. Mean relative intensities of these features were significantly reduced during the inhibition session compared with the control session (n = 37). Semi-quantitative analysis showed that the largest decrease (-85%) was observed for the ion m/z 432.3108 normalized to solanidine (m/z 398.3417). Mean relative intensities of these ions were significantly higher in the CYP2D6 normal-ultrarapid metabolizer group (n = 37) compared with the poor metabolizer group (n = 6). Solanidine intensity was more than 15 times higher in CYP2D6-deficient individuals compared with other volunteers.
The applied untargeted metabolomic strategy identified potential novel markers capable of semi-quantitatively predicting CYP2D6 activity, a promising discovery for personalized medicine.
Keywords
Biomarkers, Cytochrome P-450 CYP2D6/genetics, Cytochrome P-450 CYP2D6/metabolism, Humans, Metabolomics, Phenotype, Precision Medicine, CYP2D6, CYP450, biomarker, metabolomics, phenotyping
Pubmed
Web of science
Open Access
Yes
Create date
26/01/2021 8:28
Last modification date
09/04/2022 6:33
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