The roles of CYP2C19 and CYP3A4 in the in vitro metabolism of β-eudesmol in human liver: Reaction phenotyping and enzyme kinetics.
Atractylodes lancea (Thunb.) DC
cytochrome P450
drug metabolism
enzyme kinetics
reaction phenotyping
β-eudesmol
Journal
Pharmacology research & perspectives
ISSN: 2052-1707
Titre abrégé: Pharmacol Res Perspect
Pays: United States
ID NLM: 101626369
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
revised:
05
10
2023
received:
24
06
2023
accepted:
06
10
2023
medline:
31
10
2023
pubmed:
30
10
2023
entrez:
30
10
2023
Statut:
ppublish
Résumé
β-eudesmol is a major bioactive component of Atractylodes lancea (AL). AL has been developed as the capsule formulation of standardized AL extract for treating cholangiocarcinoma (CCA). However, the complex constituents of herbal products increase the risk of adverse drug interactions. β-eudesmol has demonstrated inhibitory effects on rCYP2C19 and rCYP3A4 in the previous research. This study aimed to identify the cytochrome P450 (CYP) isoforms responsible for the metabolism of β-eudesmol and determine the enzyme kinetic parameters and the metabolic stability of β-eudesmol metabolism in the microsomal system. Reaction phenotyping using human recombinant CYPs (rCYPs) and selective chemical inhibitors of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 was performed, and enzyme kinetics and metabolic stability were investigated using human liver microsome (HLM). The results suggest that CYP2C19 and CYP3A4 play significant roles in β-eudesmol metabolism. The disappearance half-life (t
Identifiants
pubmed: 37902256
doi: 10.1002/prp2.1149
pmc: PMC10614204
doi:
Substances chimiques
Cytochrome P-450 CYP3A
EC 1.14.14.1
Cytochrome P-450 CYP2C19
EC 1.14.14.1
beta-eudesmol
473-15-4
Cytochrome P-450 Enzyme System
9035-51-2
CYP2C19 protein, human
EC 1.14.14.1
CYP3A4 protein, human
EC 1.14.14.55
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e01149Subventions
Organisme : Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma
Organisme : Thailand Science Research and Innovation Fundamental Fund
Organisme : Thammasat University Research Fund
ID : TUFT-FF 48/2565
Organisme : The Thailand Research Fund under the Royal Golden Jubilee Ph.D. Program
ID : PHD/0095/2561
Informations de copyright
© 2023 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.
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