Which statements about drug protein binding are true?

• A. I, II, III, IV
• B. I, II, IV
• C. III, IV
• D. IV only

Answer: (D)

Protein binding is a reversible interaction where the drug attaches to plasma proteins, mainly albumin, and sometimes other proteins. Only the portion of the drug that is not bound—that is, the unbound or free fraction—can move out of the bloodstream into tissues, cross membranes, interact with targets, be metabolized, and be cleared from the body. Because binding sites on proteins can become saturated, the free fraction can change as you increase the total drug concentration—the binding process is concentration-dependent, not fixed. Additionally, two drugs can compete for the same binding sites; when one displaces another, the free concentration of the displaced drug can rise temporarily, potentially changing its effect or toxicity.

These ideas—that binding is reversible, that it can become saturated, and that only the unbound drug is pharmacologically active and subject to clearance—are what the correct statement about drug protein binding will reflect. If you share the exact wording of the four statements, I can show why the one describing these properties is the only true one and why the others don’t fit.