An epileptic patient receiving phenytoin develops acute glomerulonephritis. What change, if any, would be expected in the patient's circulating drug level?

• A. Decrease in free drug
• B. Increase in free drug
• C. Increase in protein-bound drug
• D. No change in circulating drug level

Answer: (B)

Focus on how protein binding affects drug levels. Phenytoin is highly bound to serum albumin, and only the unbound portion is pharmacologically active and available for clearance. In acute glomerulonephritis there is loss of protein in the urine, leading to hypoalbuminemia. With less albumin around, fewer binding sites are available, so a larger fraction of phenytoin remains unbound. That means the circulating active (free) drug level increases. The total drug level measured in blood can be misleadingly normal or even decreased because clearance of the unbound drug can rise, but the key point is the rise in the free fraction, which elevates the pharmacologic effect and toxicity risk.