Which type of drug can pass the blood-brain barrier despite the barriers?

• A. Hydrophilic
• B. Lipophilic
• C. Large polar
• D. Ionized

Answer: (B)

Crossing the blood-brain barrier relies on a drug’s ability to dissolve in and diffuse through the lipid membranes that line brain capillaries. Lipophilic drugs are fat-loving, so they readily dissolve in the membrane’s hydrophobic core and diffuse into the brain tissue despite the barrier. In contrast, hydrophilic, large polar, or ionized drugs don’t mix well with the lipid interior and thus cross slowly or not at all unless special transport systems are involved, which many drugs don’t have. So, the property that best predicts BBB penetration is lipophilicity, though note that some exceptions exist due to active transport or efflux mechanisms.