Which statement is true about protein-bound drugs?

• A. Both portions of the drug, bound and unbound are active
• B. The portion of the drug that is bound is inactive
• C. Binding to plasma proteins has no impact
• D. The portion of the drug that is unbound is active

Answer: (D)

Only the unbound fraction of a protein-bound drug is capable of producing a pharmacologic effect because it can cross membranes, reach receptors, and be metabolized or cleared. The portion bound to plasma proteins is generally inactive at receptor sites and acts as a reservoir that can release drug as the unbound portion is cleared. So the active drug is the unbound part. Binding does influence distribution and half-life, and changes in binding (like low albumin or competitive displacement) can raise the free drug level and toxicity risk. The statements implying that the bound portion is active or that binding has no impact aren’t accurate, since activity depends on the unbound drug and binding modulates how the drug is distributed and eliminated.