High plasma protein binding affects CNS distribution by which mechanism?

High plasma protein binding affects CNS distribution by which mechanism?

• A. Increases brain penetration by delivering more drug to brain.
• B. Reduces free drug fraction available to cross the BBB.
• C. Has no effect on CNS distribution.
• D. Increases rate of passive diffusion across BBB.

Answer: (B)

High plasma protein binding reduces CNS distribution because only the unbound fraction can cross the blood-brain barrier. When a large portion of the drug is bound to plasma proteins, the free concentration available to diffuse into the brain is lowered, slowing brain penetration. The bound portion acts as a reservoir but does not contribute to immediate brain exposure, since diffusion across the BBB depends on the unbound drug.

High plasma protein binding reduces CNS distribution because only the unbound fraction can cross the blood-brain barrier. When a large portion of the drug is bound to plasma proteins, the free concentration available to diffuse into the brain is lowered, slowing brain penetration. The bound portion acts as a reservoir but does not contribute to immediate brain exposure, since diffusion across the BBB depends on the unbound drug.