The reduction in absorption due to P-glycoprotein depends on which factors?

• A. Amount of P-glycoprotein present and its intrinsic activity
• B. Time of day
• C. Only substrate solubility
• D. Only pH of the lumen

Answer: (A)

P-glycoprotein acts as an efflux pump on the apical surface of intestinal cells, actively moving its substrates back into the lumen and thereby lowering net absorption. The extent of this reduction depends on two main factors: how much P-glycoprotein is present (its expression level) and how effectively it can transport the drug (intrinsic activity, including ATPase activity and substrate affinity). More P-gp or higher activity means more drug is pumped out and less is absorbed. Conversely, lower expression or reduced activity lessens the efflux and increases absorption. Time of day, while it can influence expression in some contexts, is not the primary determinant here; substrate solubility and luminal pH affect passive diffusion but do not define the transporter-specific reduction.