Which statement best explains why higher lipophilicity can influence P-gp interactions?

• A. More lipophilic drugs have greater likelihood to partition into the membrane where P-gp is located
• B. More lipophilic drugs are less likely to contact P-gp
• C. P-gp only transports hydrophilic compounds
• D. Lipophilicity does not affect P-gp interactions

Answer: (A)

Higher lipophilicity increases a drug’s tendency to partition into the lipid membrane where P-glycoprotein sits. Since P-gp is embedded in the cell membrane and interacts with substrates from within the bilayer, molecules that are more lipophilic spend more time in the membrane and are more likely to encounter P-gp’s binding pocket. This raises the chance of recognition and efflux, explaining why higher lipophilicity can enhance P-gp–mediated transport.

The other statements don’t fit: a more lipophilic compound doesn’t avoid contact with P-gp; P-gp can transport hydrophobic substrates as well as hydrophilic ones; and lipophilicity does influence P-gp interactions.