Human ADME of remibrutinib: rapid uptake, heavy metabolism, mainly fecal elimination
- A radiolabelled oral dose plus intravenous microdoses in healthy volunteers mapped how the covalent BTK inhibitor remibrutinib is absorbed, distributed and cleared at steady state.
- The drug was taken up quickly, spread widely into tissues and was extensively metabolised, with most elimination through the feces.
- Radioactivity recovery was incomplete after oral dosing but nearly complete after the intravenous microdose, which helps separate absorption from clearance.
- No circulating metabolite made up a major share of drug-related material, and the drug was well tolerated.
💡 Points Based on the abstract
Incomplete recovery after the oral dose but near-complete after the IV microdose suggests the loss sits in the absorption phase rather than in a tissue sink, and the microdose is what lets you separate that from clearance. For a covalent inhibitor, also ask how much label stays irreversibly on protein. Extensive metabolism with fecal dominance makes a hepatic-enzyme DDI study the sensible next step.