A patient receiving oral phenytoin 300 mg daily has a serum level of 8 microgram/mL. The dose is increased to 400 mg daily, after which the level rises to 22 microgram/mL. This disproportionate rise in concentration best reflects which property of phenytoin?
- A Autoinduction of CYP-mediated metabolism
- B Dose-dependent increase in oral bioavailability above 300 mg/day
- C Saturation of hepatic metabolism, giving zero-order kinetics at therapeutic concentrations ✓
- D Displacement from plasma proteins by its own metabolites
Correct answer: C. Saturation of hepatic metabolism, giving zero-order kinetics at therapeutic concentrations
Explanation
Phenytoin is metabolised by CYP2B9 and CYP2B19, and these enzymes approach saturation within the therapeutic range, so small dose increments cause large rises in steady-state level (Michaelis-Menten or zero-order kinetics). This is why dose changes are made in small steps. Autoinduction is the property of carbamazepine, not phenytoin, which kills distractor A. Bioavailability does not increase with dose, ruling out B.
Reference: Katzung Basic and Clinical Pharmacology, 15th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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