Often overlooked, direct intestinal excretion of drug from the blood to the intestinal mucosa is gaining more attention as a clearance pathway alongside liver metabolism, biliary and renal.
A growing number of papers are highlighting the importance of this under-explored mechanism, with a new review published in August 2025: Property-Based Prediction Uncovers Intestinal Excretion as an Elimination Route of Small-Molecule Drugs at Journal of Medicinal Chemistry by Chen et.al. that caught our attention.
After reading it, we couldn’t help but ask ourselves:
- What is the upper limit of intestinal excretion for both active and passive processes in pre-clinical species and human?
- For lipophilic, highly permeable compounds, where liver clearance dominates, how significant is the contribution of intestinal extrusion really?
- And ultimately – how many human oral drugs, with parent compound detected in the faeces, are being excreted via the intestine, rather than simply “not being absorbed” i.e. Fa ≤ 1?