Which type of drugs tend to diffuse through cell membranes most readily?

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

Answer: (C)

Cell membranes have a hydrophobic interior, so drugs that are lipophilic (nonpolar) dissolve in that lipid and diffuse across the membrane down their concentration gradient. This passive diffusion is easiest for uncharged, nonpolar molecules, which is why lipophilic drugs cross membranes readily. In contrast, hydrophilic substances don’t partition into the lipid well and cross slowly; ionic compounds are charged and are strongly hindered by the hydrophobic core; large polar molecules face even bigger barriers and typically need transporters or channels. Because of this, lipophilic drugs diffuse through membranes most readily.