The article highlights a lesser-known route of drug elimination: direct intestinal clearance, where drugs are pumped from the bloodstream back into the intestines and then excreted via feces. While liver metabolism and kidney filtration are well-known drug clearance pathways, this intestinal route has been underrecognized. Some drugs, like apixaban, show significant fecal excretion even after intravenous administration, suggesting active transport mechanisms at play.
The piece discusses how physicochemical properties like logD and pKa influence whether a drug is more likely to be cleared via the kidneys, bile, or intestines. It also notes that in humans, distinguishing between biliary and intestinal clearance is difficult due to sampling limitations, though new tools like EnteroTracker may help clarify these pathways.
Ultimately, this insight could impact drug development by adding another layer to pharmacokinetic modeling and clearance prediction.