A 30-year-old man on phenytoin 300 mg/day has a steady-state level of 8 mcg/mL. His dose is increased to 400 mg/day. At the new steady state his level is 22 mcg/mL with nystagmus and ataxia. The kinetic phenomenon responsible is:

• A Autoinduction of CYP2C9 metabolism
• B Displacement of phenytoin from albumin binding sites
• C Saturation of hepatic metabolism leading to zero-order elimination ✓
• D Dose-dependent increase in oral bioavailability

Explanation

Phenytoin follows Michaelis-Menten kinetics: at low concentrations metabolism is first order, but as levels approach the therapeutic range the hydroxylating enzymes saturate and clearance becomes dose dependent. Small dose increments can therefore produce disproportionately large rises in serum level, exactly as seen here. Autoinduction is a property of carbamazepine, not phenytoin, and protein binding displacement alters total but not free concentration.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.