Effect of CYP3A inhibitors on the pharmacokinetics of pevonedistat in patients with advanced solid tumours.

ABSTRACT:

Aims

This phase I study evaluated the effects of the moderate cytochrome P450 (CYP) 3A inhibitor fluconazole and the strong CYP3A/P-glycoprotein (P-gp) inhibitor itraconazole on the pharmacokinetics of the investigational neural precursor cell expressed, developmentally downregulated 8 (NEDD8)-activating enzyme inhibitor pevonedistat in patients with advanced solid tumours.

Methods

Patients received single doses of intravenous pevonedistat 8 mg m^-2 , alone and with fluconazole (loading: 400 mg; maintenance: 200 mg once daily), or pevonedistat 8, 15 or 20 mg m^-2 , alone and with itraconazole 200 mg once daily. Serial blood samples for pevonedistat pharmacokinetics were obtained pre- and post-infusion on days 1 (alone) and 8 (with fluconazole/itraconazole

SUBMITTER: Faessel H 

PROVIDER: S-EPMC6595297 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature