If a drug is a significant substrate for P-glycoprotein, what is the expected effect on its systemic exposure?

If a drug is a significant substrate for P-glycoprotein, what is the expected effect on its systemic exposure?

• A. Increased intensity
• B. Decreased intensity
• C. No change
• D. Initial spike then drop

Answer: (B)

P-glycoprotein acts as an intestinal efflux transporter, pumping drugs back into the gut lumen as they are absorbed. When a drug is a significant substrate, a large portion is effluxed before it can reach the bloodstream, reducing the amount that enters systemic circulation. This lowers overall systemic exposure, typically seen as a reduced AUC and often a lower peak concentration. Practically, this is why P-gp substrates can have limited oral bioavailability, and why inhibitors of P-gp can increase exposure.

P-glycoprotein acts as an intestinal efflux transporter, pumping drugs back into the gut lumen as they are absorbed. When a drug is a significant substrate, a large portion is effluxed before it can reach the bloodstream, reducing the amount that enters systemic circulation. This lowers overall systemic exposure, typically seen as a reduced AUC and often a lower peak concentration. Practically, this is why P-gp substrates can have limited oral bioavailability, and why inhibitors of P-gp can increase exposure.