If P-gp is inhibited, what happens to blood levels of a coadministered substrate?

If P-gp is inhibited, what happens to blood levels of a coadministered substrate?

• A. Decrease
• B. Increase
• C. No change
• D. Fluctuate unpredictably

Answer: (B)

P-glycoprotein is an efflux transporter that pumps certain drugs out of cells, especially in the intestinal lining, liver, kidneys, and the blood–brain barrier. Its job is to limit systemic exposure by pushing the drug back into the gut lumen or into bile/urine. When P-gp is inhibited, this pumping action is reduced, so more of the substrate drug is absorbed and less is pumped out for elimination. The result is higher circulating drug levels, meaning increased blood levels (and usually increased overall exposure, like a higher AUC and potentially a higher peak concentration). This is why coadministering a P-gp inhibitor with a P-gp substrate can raise the risk of toxicity.

P-glycoprotein is an efflux transporter that pumps certain drugs out of cells, especially in the intestinal lining, liver, kidneys, and the blood–brain barrier. Its job is to limit systemic exposure by pushing the drug back into the gut lumen or into bile/urine. When P-gp is inhibited, this pumping action is reduced, so more of the substrate drug is absorbed and less is pumped out for elimination. The result is higher circulating drug levels, meaning increased blood levels (and usually increased overall exposure, like a higher AUC and potentially a higher peak concentration). This is why coadministering a P-gp inhibitor with a P-gp substrate can raise the risk of toxicity.