What is the effect of high P-gp expression on drug absorption?

• A. More pumped back into lumen and less reach capillaries
• B. Less pumped back into lumen
• C. No change
• D. Increased permeability

Answer: (A)

High P-gp expression acts as an active efflux barrier in the intestinal lining. P-glycoprotein sits on the apical side of enterocytes and uses energy to pump drug molecules back into the intestinal lumen as they try to cross into the blood. When expression is high, more of the drug that enters the cell is returned to the lumen instead of reaching the capillaries, so net absorption into the bloodstream decreases and systemic exposure is reduced.

This aligns with the idea that increased efflux lowers effective permeability into the bloodstream. The other statements imply less pumping, no change, or increased permeability, which would not reflect the action of P-gp as an efflux transporter.