A microdosing framework for absolute bioavailability assessment of poorly soluble drugs: A case study on cold-labeled venetoclax, from chemistry to the clinic.

ABSTRACT: This work presents an end-to-end approach for assessing the absolute bioavailability of highly hydrophobic, poorly water-soluble compounds that exhibit high nonspecific binding using venetoclax as a model drug. The approach utilizes a stable labeled i.v. microdose and requires fewer resources compared with traditional approaches that use radioactive ¹⁴ C-labeled compounds. The stable labeled venetoclax and internal standard were synthesized, then an i.v. formulation was developed. In the clinical study, female subjects received a single oral dose of venetoclax 100 mg followed by a 100-µg i.v. dose of cold-labeled ¹³ C-venetoclax at the oral time of maximum concentration (T_max ). The i.v. microdose was prepared as an extemporaneous, sterile compounded soluti

SUBMITTER: Alaarg A 

PROVIDER: S-EPMC8742638 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature