Phenytoin exhibits zero-order (saturation) kinetics at therapeutic plasma concentrations. The clinical implication of this is:
- A Phenytoin half-life is constant, making dosing adjustments straightforward
- B Small dose increments at therapeutic levels can cause disproportionately large and unpredictable rises in plasma concentration, increasing risk of toxicity ✓
- C Phenytoin plasma levels are independent of dose, so no therapeutic drug monitoring is required
- D Phenytoin is eliminated at a constant rate (mg/hour) that doubles with each doubling of dose
Explanation
Phenytoin is metabolised by CYP2C9/2C19 via a saturable (Michaelis-Menten) enzyme. At low plasma concentrations, first-order kinetics apply; near the therapeutic range (10–20 mg/L), the enzyme saturates and kinetics switch to zero-order — a fixed amount is eliminated per unit time regardless of concentration. This means small dose increases (e.g., 50 mg increment) can disproportionately elevate plasma levels from therapeutic to toxic range. Therapeutic drug monitoring is essential. This is why phenytoin dose increments are kept to 25–50 mg steps near the target range.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.