Which factor would increase placental transfer of a drug?

Which factor would increase placental transfer of a drug?

• A. High ionization at physiological pH
• B. High lipophilicity and non-ionized state
• C. High molecular weight
• D. Strong binding to plasma proteins

Answer: (B)

Placental transfer is mainly driven by passive diffusion across the placental membranes, so the drug’s ability to cross depends on how permeable the membranes are to the drug and how much unbound drug is available to diffuse. Diffusion favors small, non-ionized, lipophilic molecules because they are more soluble in the lipid membranes and can move down the concentration gradient more readily. The unbound fraction matters because only free drug can partition into the membranes. Therefore, a drug that is highly lipophilic and in a non-ionized state at physiological pH will cross the placental barrier more readily. In contrast, ionized drugs diffuse poorly, large molecules encounter a size barrier, and drugs that bind tightly to plasma proteins have less free drug to diffuse, all of which reduce placental transfer.

Placental transfer is mainly driven by passive diffusion across the placental membranes, so the drug’s ability to cross depends on how permeable the membranes are to the drug and how much unbound drug is available to diffuse. Diffusion favors small, non-ionized, lipophilic molecules because they are more soluble in the lipid membranes and can move down the concentration gradient more readily. The unbound fraction matters because only free drug can partition into the membranes.

Therefore, a drug that is highly lipophilic and in a non-ionized state at physiological pH will cross the placental barrier more readily. In contrast, ionized drugs diffuse poorly, large molecules encounter a size barrier, and drugs that bind tightly to plasma proteins have less free drug to diffuse, all of which reduce placental transfer.