A Physiologically Based Pharmacokinetic Model of Ketoconazole and Its Metabolites as Drug-Drug Interaction Perpetrators.

ABSTRACT: 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^® and MoBi^® using 53 plasma concentration-time profiles. With 7 out of 7 (7/7) DFI AUC_last and DFI C_max ratios wi

SUBMITTER: Marok FZ 

PROVIDER: S-EPMC9965990 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature