A drug has zero-order kinetics at therapeutic doses. Which statement best describes the clinical implication?
- A A fixed fraction of drug is eliminated per unit time, so dose increments cause predictable proportional changes in steady-state levels
- B The drug's half-life increases proportionally with plasma concentration
- C A fixed amount of drug is eliminated per unit time; small dose increases can cause disproportionately large rises in plasma concentration, narrow therapeutic window ✓
- D Protein binding is saturable causing variable free-drug fraction
Correct answer: C. A fixed amount of drug is eliminated per unit time; small dose increases can cause disproportionately large rises in plasma concentration, narrow therapeutic window
Explanation
Zero-order (Michaelis-Menten / capacity-limited / saturation) kinetics means the elimination mechanism is saturated — a constant absolute amount (not fraction) is cleared per unit time. When doses are increased slightly above the saturation point, plasma concentrations rise steeply and unpredictably because extra drug cannot be eliminated faster. This characterizes phenytoin, ethanol, and high-dose aspirin, all of which have narrow safety margins at therapeutic doses. In first-order kinetics, a constant fraction is eliminated.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.