The 1β-Hydroxy-Deoxycholic Acid to Deoxycholic Acid Urinary Metabolic Ratio: Toward a Phenotyping of CYP3A Using an Endogenous Marker?

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_8186FF4285F1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The 1β-Hydroxy-Deoxycholic Acid to Deoxycholic Acid Urinary Metabolic Ratio: Toward a Phenotyping of CYP3A Using an Endogenous Marker?
Journal
Journal of personalized medicine
Author(s)
Magliocco G., Desmeules J., Bosilkovska M., Thomas A., Daali Y.
ISSN
2075-4426 (Print)
ISSN-L
2075-4426
Publication state
Published
Issued date
20/02/2021
Peer-reviewed
Oui
Volume
11
Number
2
Pages
150
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
In this study, we assessed the potential use of the 1β-hydroxy-deoxycholic acid (1β-OH-DCA) to deoxycholic acid (DCA) urinary metabolic ratio (UMR) as a CYP3A metric in ten male healthy volunteers. Midazolam (MDZ) 1 mg was administered orally at three sessions: alone (control session), after pre-treatment with fluvoxamine 50 mg (12 h and 2 h prior to MDZ administration), and voriconazole 400 mg (2 h before MDZ administration) (inhibition session), and after a 7-day pre-treatment with the inducer rifampicin 600 mg (induction session). The 1β-OH-DCA/DCA UMR was measured at each session, and correlations with MDZ metrics were established. At baseline, the 1β-OH-DCA/DCA UMR correlated significantly with oral MDZ clearance (r = 0.652, p = 0.041) and C <sub>max</sub> (r = -0.652, p = 0.041). In addition, the modulation of CYP3A was reflected in the 1β-OH-DCA/DCA UMR after the intake of rifampicin (induction ratio = 11.4, p < 0.01). During the inhibition session, a non-significant 22% decrease in 1β-OH-DCA/DCA was observed (p = 0.275). This result could be explained by the short duration of CYP3A inhibitors intake fixed in our clinical trial. Additional studies, particularly involving CYP3A inhibition for a longer period and larger sample sizes, are needed to confirm the 1β-OH-DCA/DCA metric as a suitable CYP3A biomarker.
Keywords
CYP450, phenotyping, CYP3A, bile acid, biomarker
Pubmed
Web of science
Open Access
Yes
Create date
22/02/2021 13:55
Last modification date
13/03/2021 7:22
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