Which factor can cause displacement leading to changes in fu?

• A. Temperature
• B. Dose
• C. Competing drugs
• D. Route of administration

Answer: (C)

Displacement in plasma protein binding happens when two drugs compete for the same binding sites on proteins like albumin. The unbound fraction (fu) is the part of a drug that is free to distribute into tissues and be cleared. When a second drug with affinity for those sites is present, it can push the first drug off the sites, increasing fu. That rise in fu can then alter distribution and clearance of the displaced drug.

Competing drugs are the factor that directly cause this displacement. Temperature can tweak binding a bit, but it’s not the typical driver of displacement in clinical PK. Dose can change overall levels and, at very high concentrations, may saturate binding sites, but that’s not the same mechanism as competitive displacement. Route of administration doesn’t cause displacement in binding.