A patient with epilepsy is maintained on phenytoin 300 mg/day with a serum level of 12 micrograms/mL (therapeutic range 10 to 20). The dose is increased to 400 mg/day to improve control. Which kinetic property of phenytoin best predicts that the resulting serum level will rise disproportionately?
- A Extensive plasma protein binding
- B Saturable hepatic metabolism following Michaelis-Menten kinetics ✓
- C Enterohepatic recirculation of the glucuronide metabolite
- D Autoinduction of CYP-mediated clearance
Correct answer: B. Saturable hepatic metabolism following Michaelis-Menten kinetics
Explanation
Phenytoin is metabolised by CYP2C9 and CYP2C19 by enzymes that approach saturation within the therapeutic range. Once Vmax is reached, small dose increments produce large, unpredictable rises in serum concentration because elimination rate no longer increases proportionally with concentration. Autoinduction is characteristic of carbamazepine, not phenytoin. Protein binding affects total versus free levels but does not explain disproportionate accumulation.
Reference: Katzung Basic and Clinical Pharmacology, 16th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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