Back to Search
Start Over
Phase I study of orally administered 14Carbon-isotope labelled-vistusertib (AZD2014), a dual TORC1/2 kinase inhibitor, to assess the absorption, metabolism, excretion, and pharmacokinetics in patients with advanced solid malignancies
- Source :
- Cancer Chemotherapy and Pharmacology. 83:787-795
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- Vistusertib is an orally bioavailable dual target of rapamycin complex (TORC) 1/2 kinase inhibitor currently under clinical investigation in various solid tumour and haematological malignancy settings. The pharmacokinetic, metabolic and excretion profiles of 14Carbon-isotope (14C)-labelled vistusertib were characterised in this open-label phase I patient study. Four patients with advanced solid malignancies received a single oral solution dose of 14C-labelled vistusertib. Blood, urine, faeces, and saliva samples were collected at various time points during the 8-day in-patient period of the study. Safety and preliminary efficacy were also assessed. 14C-labelled vistusertib was rapidly absorbed following administration (time to maximum concentration (Tmax) 90% of radioactivity was recovered with the majority recovered as metabolites in faeces (on average 80% vs. 12% recovered in urine). The majority of circulating radioactivity (~ 78%) is unchanged vistusertib. Various morpholine-ring oxidation metabolites and an N-methylamide circulate at low concentrations [each
- Subjects :
- 0301 basic medicine
Pharmacology
Cancer Research
Saliva
business.industry
Urine
Toxicology
medicine.disease
Bioavailability
Excretion
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Oncology
Pharmacokinetics
030220 oncology & carcinogenesis
Medicine
Pharmacology (medical)
business
Adverse effect
Stomatitis
ADME
Subjects
Details
- ISSN :
- 14320843 and 03445704
- Volume :
- 83
- Database :
- OpenAIRE
- Journal :
- Cancer Chemotherapy and Pharmacology
- Accession number :
- edsair.doi...........7d7583ffcf041884d9fa5459d8d420be