A patient receives phenytoin 300 mg/day with a steady-state level of 10 mcg/mL. The dose is increased to 400 mg/day to improve control. Which kinetic property best explains why the resulting plasma level may rise disproportionately, even above 25 mcg/mL?

• A Phenytoin exhibits saturable metabolism following Michaelis-Menten kinetics ✓
• B Phenytoin undergoes autoinduction of its own metabolism
• C Phenytoin is a competitive substrate of CYP2C19 with low extraction ratio
• D Phenytoin has a very large volume of distribution that expands at higher doses

Explanation

At therapeutic concentrations the enzymes metabolising phenytoin approach saturation, so small dose increments produce disproportionate rises in plasma concentration because elimination rate no longer increases proportionally with concentration (Michaelis-Menten or capacity-limited kinetics). This is why dose changes near the therapeutic range should be small and levels monitored. Autoinduction is characteristic of carbamazepine, not phenytoin. Volume of distribution does not change with dose.

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

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