ArticleDrug metabolism and disposition: the biological fate of chemicals2025
1β-Hydroxydeoxycholic acid as an endogenous biomarker in human plasma for assessment of drug-drug interaction with moderate CYP3A inhibitor.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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6 authors.
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Abstract
1β-Hydroxydeoxycholic acid (1β-OH DCA) in plasma has been shown to be a promising biomarker to assess drug-drug interaction (DDI) with a strong CYP3A inducer or a strong CYP3A inhibitor. The changes in total 1β-OH DCA (sum of 1β-OH DCA, 1β-OH glycine deoxycholic acid, and 1β-OH taurine deoxycholic acid equivalents) were more significant than those observed from 4β-hydroxycholesterol, which has been limited to the identification of CYP3A inducers, not CYP3A inhibitors. The significant reduction in total 1β-OH DCA in response to strong CYP3A inhibitors led us to further explore its utility as a biomarker for DDI with moderate CYP3A inhibitors. Building from the previously reported biomarker method, we further improved the quantified assay by introducing the stable labeled 1β-OH DCA internal standard, optimizing the extraction and chromatographic conditions for better sample cleanup and separation of these biomarkers from other endogenous components in human plasma. Inhibition with a moderate CYP3A inhibitor fluconazole resulted in notable changes in these biomarkers, with 39%, 39%, and 18% reductions in total 1β-OH DCA C
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