Do lipophilic drugs reach equilibrium faster in brain or muscle? why?

• A. Brain, because they are lipophilic and brain is highly perfused
• B. Muscle, because they are more hydrophilic
• C. Brain, because of lower perfusion
• D. Muscle, because the blood-brain barrier impedes entry

Answer: (A)

Equilibrium with the blood for a lipophilic drug is fastest where blood flow is highest and the drug can readily cross barriers into the tissue. The brain has very high perfusion, so blood delivers drug there quickly. Lipophilic drugs cross cell membranes and, to a degree, the blood-brain barrier more easily than hydrophilic ones, allowing rapid entry into brain tissue. Because of this combination—high cerebral blood flow and good brain penetration—the brain reaches distribution equilibrium with the blood faster than muscle. In muscle, perfusion is robust but not as high as in the brain, so equilibration proceeds more slowly.