Which of the following would have the shortest time to equilibrium for a lipophilic drug?

• A. Fat
• B. Brain
• C. Bone
• D. Skeletal muscle

Answer: (B)

Time to reach equilibrium for a lipophilic drug is mainly governed by how quickly the tissue is exposed to blood (tissue perfusion) and how easily the drug can cross barriers into that tissue. The brain has the highest perfusion among tissues and, for lipophilic drugs, crosses the blood–brain barrier readily. This combination means the brain heartbeat-fast enough to rapidly equilibrate with plasma.

Fat tissue, despite its large lipid content, receives blood more slowly, so it takes longer for a lipophilic drug to distribute into and reach equilibrium with that reservoir. Bone has poor blood flow, further delaying distribution. Skeletal muscle has decent blood flow but not as high as the brain, so its equilibration is slower than brain for a lipophilic compound.

Therefore, the brain would reach equilibrium with the plasma fastest because of its very high blood flow and the ease with which lipophilic drugs cross into brain tissue.