In which organ is P-glycoprotein primarily responsible for reducing drug absorption into systemic circulation?

• A. Stomach
• B. Brain
• C. Intestine
• D. Skin

Answer: (C)

The key idea is that P-glycoprotein acts as an intestinal efflux pump that directly limits how much drug gets into the bloodstream after oral dosing. It sits on the apical (lumen-facing) surface of intestinal epithelial cells and uses energy from ATP to move many drugs back into the intestinal lumen. Because of this, a large portion of the drug is pumped back before it can reach systemic circulation, reducing oral bioavailability.

This is why the intestine is the primary organ where P-glycoprotein reduces absorption into the bloodstream. While P-gp is also present at other barriers, such as the blood-brain barrier, its role there is to restrict entry into the brain rather than to control overall systemic absorption from an oral dose. The stomach and skin have other dominant factors influencing absorption—gastric conditions and barrier properties like the stratum corneum, respectively—so they are not the main sites where P-gp reduces systemic absorption.