Phenytoin exhibits zero-order (saturation) kinetics at therapeutic doses. The clinical implication is:
- A Small increases in dose produce disproportionately large and unpredictable rises in plasma concentration, requiring very small dose titration steps ✓
- B Small increases in dose cause proportionally small increases in plasma concentration
- C Phenytoin plasma concentration increases linearly with dose at all therapeutic concentrations
- D Phenytoin has a predictable, fixed half-life of 24 hours regardless of dose
Correct answer: A. Small increases in dose produce disproportionately large and unpredictable rises in plasma concentration, requiring very small dose titration steps
Explanation
At therapeutic concentrations, phenytoin saturates its hepatic CYP2C9/CYP2C19 metabolism (Km ≈ 5–10 mg/L, within the therapeutic range of 10–20 mg/L). Once Michaelis-Menten kinetics are saturated, the elimination rate becomes constant (zero-order, fixed amount per unit time regardless of concentration). Even a 10–15% dose increase can cause plasma levels to double or triple, leading to toxicity (nystagmus, ataxia, diplopia). This narrow therapeutic-index, dose-dependent kinetics makes phenytoin one of the most difficult antiepileptics to dose accurately.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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