Which statement about the relationship between albumin and phenytoin levels is true?

• A. Low albumin leads to lower phenytoin levels
• B. Albumin levels do not affect phenytoin levels
• C. Low albumin leads to higher free phenytoin levels
• D. High albumin leads to higher phenytoin levels

Answer: (C)

Phenytoin’s activity depends on the free (unbound) portion because it is highly bound to albumin. When albumin is low, there are fewer binding sites available, so more phenytoin remains unbound and active. This raises the amount of pharmacologically active drug even if the total phenytoin level isn’t dramatically high, which is why low albumin leads to higher free phenytoin levels. Conversely, higher albumin would bind more drug and reduce the free fraction, not increase it. Due to this protein binding, total phenytoin measurements can be misleading in hypoalbuminemia, so clinicians may need to assess or interpret free phenytoin levels or adjust dosing accordingly.