When Drug A, a substrate for P-glycoprotein, and Drug B, an inhibitor of P-glycoprotein, are administered together, several interactions can occur due to the influence of P-glycoprotein on drug transport

QUESTION

Drug A is a substrate for P glycoprotein. Drug B inhibits P-glycoprotein. Which of the following could happen if Drug A and Drug B are given together?

  1. Increase transport of Drug A into the brain
  2. Decrease transport of drug B into the brain
  3. Increase transport of Drug A across the intestinal cells into the blood
  4. Decreased transport of Drug B across the intestinal cells into the blood
  5. A and c

ANSWER

When Drug A, a substrate for P-glycoprotein, and Drug B, an inhibitor of P-glycoprotein, are administered together, several interactions can occur due to the influence of P-glycoprotein on drug transport. Let’s explore the possible outcomes:

1. Increase Transport of Drug A into the Brain:
This is a plausible outcome when Drug B inhibits P-glycoprotein. Inhibition of P-glycoprotein can lead to reduced efflux (removal) of Drug A from the brain, resulting in higher concentrations of Drug A within the central nervous system.

2. Decrease Transport of Drug B into the Brain:
This option is not directly related to the interaction between Drug A and Drug B. P-glycoprotein inhibition by Drug B is more likely to affect the transport of other drugs, such as Drug A, into the brain rather than its own transport.

3. Increase Transport of Drug A Across the Intestinal Cells into the Blood:
This is another plausible outcome. Inhibition of P-glycoprotein by Drug B at the intestinal level can increase the absorption of Drug A from the gastrointestinal tract into the bloodstream. This can lead to higher systemic concentrations of Drug A.

4. Decreased Transport of Drug B Across the Intestinal Cells into the Blood:
This is also a potential outcome. P-glycoprotein inhibition by Drug B may result in reduced efflux of Drug B from the intestinal cells, leading to higher concentrations of Drug B in the gut lumen and decreased absorption into the bloodstream.

5. A and C (Increase transport of Drug A into the brain and Increase transport of Drug A across the intestinal cells into the blood):
This option combines the two most likely outcomes of the interaction between Drug A and Drug B. It suggests that the inhibition of P-glycoprotein by Drug B can lead to increased transport of Drug A both into the brain and across intestinal cells into the blood.

In summary, when Drug A and Drug B are given together, the interaction primarily involves the inhibition of P-glycoprotein by Drug B. This inhibition can result in increased transport of Drug A into the brain and enhanced absorption of Drug A from the intestinal cells into the bloodstream. Therefore, option “A and C” is the most comprehensive answer, considering the likely consequences of this drug interaction.

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