Which disease state would most likely increase fu for drugs that are normally highly protein-bound?

• A. Hyperalbuminemia
• B. Hyperglycemia
• C. Hypoglycemia
• D. Hypoalbuminemia

Answer: (D)

When a drug is normally highly protein-bound, most of it is tied up to albumin, leaving only a small unbound fraction (fu) to exert effect and be cleared. If albumin levels drop, as in hypoalbuminemia, there are fewer binding sites available. That reduces binding and increases the unbound fraction. The higher fu means more active drug in circulation and more substrate for clearance, which can raise both pharmacologic effect and the potential for toxicity. Hyperalbuminemia would do the opposite by binding more drug and lowering fu. Blood glucose levels don’t directly alter albumin binding, so they don’t meaningfully change fu for these drugs.