Genetic variations of CYP3A4 on the metabolism of itraconazole in vitro.
COVID-19
CYP3A4
Drug metabolism
Itraconazole
Protein variants
Journal
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
ISSN: 1873-6351
Titre abrégé: Food Chem Toxicol
Pays: England
ID NLM: 8207483
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
12
08
2023
revised:
11
10
2023
accepted:
12
10
2023
medline:
6
11
2023
pubmed:
21
10
2023
entrez:
20
10
2023
Statut:
ppublish
Résumé
Itraconazole is a triazole anti-infective drug that has been proven to prevent and treat a variety of fungal and viral infections and has been considered to be a potential therapeutic remedy for COVID-19 treatment. In this study, we aimed to completely evaluate the impacts of Cytochrome P450 3A4 (CYP3A4) variant proteins and drug interactions on the metabolism of itraconazole in recombinant insect microsomes, and to characterize the potential mechanism of substrate selectivity. Incubations with itraconazole (0.2-15 μM) in the presence/absence of lopinavir or darunavir were assessed by CYP3A4 variants, and the metabolite hydroxyitraconazole concentrations were measured by UPLC-MS/MS. Our data showed that when compared with CYP3A4.1, 4 variants (CYP3A4.9, .10, .28 and .34) displayed no significant differences, and 3 variants (CYP3A4.14, .15 and .19) exhibited increased intrinsic clearance (CL
Identifiants
pubmed: 37863381
pii: S0278-6915(23)00503-3
doi: 10.1016/j.fct.2023.114101
pii:
doi:
Substances chimiques
Itraconazole
304NUG5GF4
Cytochrome P-450 CYP3A
EC 1.14.14.1
Lopinavir
2494G1JF75
Darunavir
YO603Y8113
CYP3A4 protein, human
EC 1.14.14.55
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
114101Informations de copyright
Copyright © 2023 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.