An integrated assessment of the ADME properties of the CDK4/6 Inhibitor ribociclib utilizing preclinical in vitro, in vivo, and human ADME data.

ABSTRACT: Ribociclib (LEE011, Kisqali ®) is a highly selective small molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), which has been approved for the treatment of advanced or metastatic breast cancer. A human ADME study was conducted in healthy male volunteers following a single oral dose of 600 mg [¹⁴ C]-ribociclib. Mass balance, blood and plasma radioactivity, and plasma ribociclib concentrations were measured. Metabolite profiling and identification was conducted in plasma, urine, and feces. An assessment integrating the human ADME results with relevant in vitro and in vivo non-clinical data was conducted to provide an estimate of the relative contributions of various clearance pathways of the compound. Ribociclib is moderately to highly absorbed across species (approx.

SUBMITTER: James AD 

PROVIDER: S-EPMC7287031 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature