A Physiologically Based Pharmacokinetic Model of Ketoconazole and Its Metabolites as Drug-Drug Interaction Perpetrators.
P-glycoprotein (P-gp)
cytochrome P450 3A4 (CYP3A4)
drug–drug interaction
drug–food interaction
ketoconazole
metabolites
physiologically based pharmacokinetic (PBPK) modeling
reversible inhibition
Journal
Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003
Informations de publication
Date de publication:
17 Feb 2023
17 Feb 2023
Historique:
received:
23
12
2022
revised:
06
02
2023
accepted:
13
02
2023
entrez:
25
2
2023
pubmed:
26
2
2023
medline:
26
2
2023
Statut:
epublish
Résumé
The antifungal ketoconazole, which is mainly used for dermal infections and treatment of Cushing's syndrome, is prone to drug-food interactions (DFIs) and is well known for its strong drug-drug interaction (DDI) potential. Some of ketoconazole's potent inhibitory activity can be attributed to its metabolites that predominantly accumulate in the liver. This work aimed to develop a whole-body physiologically based pharmacokinetic (PBPK) model of ketoconazole and its metabolites for fasted and fed states and to investigate the impact of ketoconazole's metabolites on its DDI potential. The parent-metabolites model was developed with PK-Sim
Identifiants
pubmed: 36840001
pii: pharmaceutics15020679
doi: 10.3390/pharmaceutics15020679
pmc: PMC9965990
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Federal Ministry of Education and Research
ID : 031L0161C
Organisme : Federal Ministry of Education and Research
ID : 031L0188D
Organisme : European Commission Horizon 2020 UPGx
ID : 668353
Organisme : Deutsche Forschungsgemeinschaft
ID : EXC 2180-390900677
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