A 30-year-old man on phenytoin 300 mg/day has a steady-state level of 11 micrograms/mL. The dose is raised to 350 mg/day. Three weeks later he develops nystagmus and slurred speech, and the level is 27 micrograms/mL. This disproportionate rise is best explained by:
- A Autoinduction of hepatic metabolism
- B Saturable, capacity-limited hepatic metabolism following Michaelis-Menten kinetics ✓
- C Displacement of phenytoin from plasma proteins
- D Accumulation of an active metabolite
Correct answer: B. Saturable, capacity-limited hepatic metabolism following Michaelis-Menten kinetics
Explanation
Phenytoin is metabolized by CYP2C9 and CYP2C19 through a system that becomes saturated at concentrations within the therapeutic range. Once the Vmax is approached, small dose increments produce large, nonlinear rises in plasma concentration, so dose changes must be small and guided by levels. Autoinduction is characteristic of carbamazepine, protein displacement alters total but not free levels, and phenytoin has no active metabolite.
Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.