A 30-year-old man on phenytoin has a steady-state level of 12 mcg/mL. His physician increases the daily dose by 50 mg to control breakthrough seizures. Two weeks later he develops horizontal nystagmus and slurred speech, and the level is now 28 mcg/mL. The kinetic property of phenytoin responsible is:

• A First-order metabolism with a short half-life requiring frequent dosing
• B Enterohepatic recirculation prolonging absorption
• C Autoinduction of CYP2C9 increasing clearance over time
• D Dose-dependent elimination due to saturable hepatic hydroxylation ✓

Explanation

Phenytoin follows Michaelis-Menten (saturable) kinetics because CYP2C9-mediated para-hydroxylation approaches capacity within the therapeutic range. Once channels are saturated, small dose increments produce disproportionately large rises in plasma concentration, so levels must be titrated in small steps. Autoinduction is characteristic of carbamazepine, not phenytoin, and enterohepatic recycling does not explain the nonlinear dose-level relationship.

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

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