A patient on phenytoin for epilepsy shows zero-order kinetics at therapeutic doses. This is because:
- A Phenytoin has a very large volume of distribution that saturates tissue binding sites
- B The hepatic CYP2C9/CYP2C19 enzymes responsible for phenytoin hydroxylation become saturated within the therapeutic range, causing dose-dependent (Michaelis-Menten) kinetics ✓
- C Phenytoin undergoes enterohepatic circulation, which slows its elimination non-linearly
- D Phenytoin is actively secreted by renal tubules, and the transporter saturates at therapeutic concentrations
Correct answer: B. The hepatic CYP2C9/CYP2C19 enzymes responsible for phenytoin hydroxylation become saturated within the therapeutic range, causing dose-dependent (Michaelis-Menten) kinetics
Explanation
Phenytoin is metabolised by CYP2C9 and CYP2C19 via para-hydroxylation, and these enzymes have a low Km and limited Vmax. Within the therapeutic range (10–20 mg/L), the enzymes are nearly saturated, so metabolism follows zero-order (saturation) kinetics — a small dose increase causes a disproportionately large rise in plasma levels. This narrow therapeutic window requires careful titration.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.