A drug is 90% protein-bound in plasma. It is displaced from albumin by a second drug, increasing the free fraction from 10% to 20%. Assuming rapid redistribution and normal elimination, the new steady-state free-drug concentration compared to baseline would be:

• A Doubled, since free fraction doubled
• B Permanently doubled, as protein binding is irreversible once displaced
• C Halved due to compensatory increase in total plasma concentration
• D Transiently increased but returns to the same free concentration at the new steady state because clearance increases proportionally ✓

Explanation

Displacement from protein binding transiently increases free-drug concentration. However, because only the free drug is available for metabolism and renal filtration, increased free fraction also increases clearance. For most drugs, the new steady-state free-drug concentration returns to approximately the original level, but total plasma concentration decreases (less bound drug). Clinically significant interactions from protein binding displacement are rare and transient unless the drug also has a very narrow therapeutic index and other PK changes compound the effect.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.