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Phenytoin – Zero-Order Kinetics — SCE Neurology MCQ

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HardEpilepsy & Seizure DisordersPhenytoin – Zero-Order KineticsSCE Neurology

A 50-year-old man with epilepsy on phenytoin has a phenytoin level of 25 mg/L (therapeutic 10–20 mg/L). His neurologist reduces the dose from 350 mg to 300 mg daily. Two weeks later his level drops to 9 mg/L and he has a seizure. What pharmacokinetic property of phenytoin explains this?

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Correct answer: C — Zero-order (saturation/non-linear) kinetics — small dose changes produce disproportionately large changes in plasma concentration near the therapeutic range

Phenytoin exhibits zero-order (saturation) kinetics at therapeutic concentrations — the hepatic enzymes responsible for its metabolism (primarily CYP2C9) become saturated. This means that small dose changes can produce disproportionately large changes in plasma levels. A decrease from 350 to 300 mg (14% reduction) caused the level to drop from 25 to 9 mg/L (64% reduction). Similarly, small dose increases can cause toxic levels. This is why phenytoin dose adjustments should be made in small increments (25–50 mg). A: First-order kinetics would produce proportional changes. C: Absorption is not dose-dependent. D: The dose change caused the level change. E: Phenytoin induces CYP3A4 (other drug metabolism) but does not significantly auto-induce.

Reference: BNF – Phenytoin Pharmacokinetics; NICE NG217