Which factor affects volume of distribution by determining how much drug is free to cross membranes?

Which factor affects volume of distribution by determining how much drug is free to cross membranes?

• A. Lipid Solubility
• B. Protein Binding
• C. Molecular Size
• D. Blood-Brain Barrier Permeability

Answer: (B)

Volume of distribution is driven by how much drug is free to cross membranes, because only the unbound drug can diffuse out of the plasma into tissues. Protein binding controls this unbound fraction: when a drug is highly protein-bound, only a small portion is free, so it doesn’t distribute widely outside the blood; this yields a smaller apparent Vd. Conversely, if a drug has low protein binding, more of it is free to cross membranes, distributing into tissues and producing a larger Vd. Lipid solubility helps the free drug cross membranes, but the amount that can move across is limited by how much is unbound, which is set by protein binding.

Volume of distribution is driven by how much drug is free to cross membranes, because only the unbound drug can diffuse out of the plasma into tissues. Protein binding controls this unbound fraction: when a drug is highly protein-bound, only a small portion is free, so it doesn’t distribute widely outside the blood; this yields a smaller apparent Vd. Conversely, if a drug has low protein binding, more of it is free to cross membranes, distributing into tissues and producing a larger Vd. Lipid solubility helps the free drug cross membranes, but the amount that can move across is limited by how much is unbound, which is set by protein binding.