A 30-year-old man on phenytoin 300 mg/day has a steady-state level of 12 mcg/mL. His physician increases the dose to 350 mg/day. Three weeks later he develops ataxia and nystagmus, and the level is 26 mcg/mL. The pharmacokinetic explanation is:
- A Saturable hepatic metabolism causing zero-order elimination near therapeutic levels ✓
- B Autoinduction of CYP2C9 by phenytoin
- C Displacement of phenytoin from albumin by endogenous metabolites
- D Progressive renal accumulation because 80% of phenytoin is excreted unchanged
Correct answer: A. Saturable hepatic metabolism causing zero-order elimination near therapeutic levels
Explanation
Phenytoin follows Michaelis-Menten kinetics: at therapeutic concentrations the hepatic enzymes (mainly CYP2C9) approach saturation, so small increments in dose produce disproportionately large rises in plasma level. This is why dose changes are made in small steps of 25 to 50 mg. Option B is wrong because autoinduction is characteristic of carbamazepine, and option D is false since about 95% of phenytoin is hepatically metabolized with negligible renal excretion of unchanged drug.
Reference: Katzung Basic and Clinical Pharmacology, 15th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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