A 24-year-old man on phenytoin 300 mg/day has a free serum level just below the target range. The physician increases the dose to 330 mg/day. Two weeks later he develops nystagmus and slurred speech. Which kinetic property of phenytoin best explains this disproportionate rise in levels?

• A Autoinduction of CYP3A4 metabolism
• B Displacement from albumin binding sites by endogenous substrates
• C Michaelis-Menten (saturable) kinetics near the therapeutic range ✓
• D Dose-dependent reduction in oral bioavailability

Explanation

Phenytoin is metabolised by saturable hepatic hydroxylation, so within and above the therapeutic range small increments in dose produce large rises in plasma concentration because clearance falls as enzymes approach Vmax. This Michaelis-Menten behaviour means a 10% dose change can double steady-state levels. Autoinduction is a property of carbamazepine, not phenytoin, which eliminates option A. Albumin displacement changes total but not free levels.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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