What role do active transporters such as P-glycoprotein play in distribution?

• A. They always increase CNS penetration
• B. They can limit CNS entry and promote tissue uptake depending on tissue expression
• C. They only affect renal clearance
• D. They have no effect on distribution

Answer: (B)

Active transporters like P-glycoprotein shape how a drug distributes by moving it across membranes using energy, and where they are expressed determines the direction and extent of that movement. At the blood–brain barrier, P-gp pumps many drugs back into the blood, limiting entry into the CNS. In other tissues, where P-gp is present on different faces of the cells, it can drive movement into excretory pathways (like bile or urine) or otherwise alter how much drug accumulates in that tissue. So, depending on the tissue distribution of the transporter, it can both restrict CNS penetration and influence distribution to other tissues.