Which change is most likely to increase fu in disease?

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

Answer: (D)

The key idea is that fu, the fraction of drug that is unbound, depends on how much binding capacity is available from plasma proteins like albumin. When albumin levels fall in disease (hypoalbuminemia), there are fewer binding sites for drugs, so a larger portion of the drug remains unbound. That increase in the unbound fraction raises fu, making more drug pharmacologically active and more available for distribution and clearance.

Hyperalbuminemia would do the opposite by providing more binding sites, reducing fu. Changes in blood glucose levels don’t directly change the amount of albumin binding, so they don’t typically have a major impact on fu.