A patient on phenytoin develops double vision, nystagmus, and ataxia. The plasma level is in the toxic range. Phenytoin's concentration-dependent kinetics (saturation kinetics) means that a small dose reduction will:

• A Cause a proportional small reduction in plasma level (first-order kinetics as usual)
• B Have no effect because phenytoin is renally excreted unchanged
• C Increase plasma levels further by inhibiting hepatic CYP2C9
• D Cause a disproportionately large fall in plasma level due to shift toward first-order kinetics ✓

Explanation

Phenytoin exhibits Michaelis-Menten (zero-order, saturable, non-linear) kinetics at therapeutic doses because CYP2C9/2C19 enzymes become saturated. When plasma level is in the toxic-saturation range, a small dose reduction shifts metabolism from zero-order toward first-order kinetics, causing a disproportionately large fall in plasma concentration. Conversely, small dose increments near saturation cause disproportionate rises — the basis for phenytoin's notoriously narrow therapeutic index in clinical dosing.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.