Which statement correctly describes the distribution limitations for polar vs lipophilic drugs?

Which statement correctly describes the distribution limitations for polar vs lipophilic drugs?

• A. Polar molecules are perfusion-limited; lipophilic are permeability-limited
• B. Polar molecules are permeability-limited; lipophilic are perfusion-limited
• C. Both are perfusion-limited
• D. Both are permeability-limited

Answer: (B)

Distribution into tissues can be limited by either how fast blood reaches the tissue (perfusion) or by how easily the drug crosses membranes (permeability). Polar, hydrophilic drugs cross lipid membranes poorly, so their rate of tissue distribution depends mainly on the membranes’ permeability—making distribution permeability-limited. Lipophilic drugs cross membranes readily, so their distribution is governed more by how much blood can be delivered to the tissue—making distribution perfusion-limited. This matches the idea that polar drugs are permeability-limited and lipophilic drugs are perfusion-limited.

Distribution into tissues can be limited by either how fast blood reaches the tissue (perfusion) or by how easily the drug crosses membranes (permeability). Polar, hydrophilic drugs cross lipid membranes poorly, so their rate of tissue distribution depends mainly on the membranes’ permeability—making distribution permeability-limited. Lipophilic drugs cross membranes readily, so their distribution is governed more by how much blood can be delivered to the tissue—making distribution perfusion-limited. This matches the idea that polar drugs are permeability-limited and lipophilic drugs are perfusion-limited.