A microdosing framework for absolute bioavailability assessment of poorly soluble drugs: A case study on cold‐labeled venetoclax, from chemistry to the clinic
Clinical and Translational Science January 8, 2022 Amr Alaarg, Rajeev Menon, David Rizzo et al.
A new method using a stable labeled intravenous microdose accurately measured the absolute bioavailability of venetoclax, a highly hydrophobic, poorly water-soluble drug. In a clinical study, female subjects received a single 100 mg oral dose of venetoclax followed by a 100 µg intravenous dose of 13C-venetoclax at the time of peak oral concentration. Plasma samples collected over 72 hours showed the absolute bioavailability of venetoclax under fasting conditions was 5.4%. The low extraction ratio of 0.06 indicates that transfer from enterocytes into the liver limits bioavailability. This approach avoids radioactive labeling and can be applied to similar compounds to guide formulation development.