A 25-year-old man with epilepsy is started on phenytoin. The drug exhibits zero-order kinetics at therapeutic doses. Which of the following best describes the clinical implication of this property?

• A Half-life remains constant regardless of dose
• B Metabolism is primarily via glucuronidation
• C Steady-state concentration is achieved within 24 hours
• D Small dose increases can lead to large, unpredictable rises in plasma concentration ✓

Explanation

Phenytoin follows saturable Michaelis-Menten metabolism. At therapeutic doses, the enzyme system is near saturation, so small increments in dose can cause disproportionately large increases in plasma concentration, leading to toxicity. This necessitates careful therapeutic drug monitoring. The half-life becomes dose-dependent and prolongs as levels rise.

Reference: Katzung & Trevor's Pharmacology Examination and Board Review, 13th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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