Which of the following drugs exhibits zero-order kinetics at therapeutic concentrations?

Explanation

## Zero-Order Kinetics: Saturable Metabolism **Key Point:** Zero-order kinetics occurs when the **elimination pathway is saturated** at therapeutic concentrations, making elimination rate **independent of drug concentration**. ### Drugs with Zero-Order Kinetics at Therapeutic Doses: | Drug | Mechanism | Saturation Point | |---|---|---| | **Aspirin (high dose)** | Saturation of hepatic conjugation (glycine/salicylate pathway) | >1 g/dose | | **Ethanol** | Saturation of alcohol dehydrogenase | Physiological levels | | **Phenytoin** | Saturation of hepatic CYP2C9 metabolism | Therapeutic range | | **Warfarin** | Saturation of CYP2C9 | Therapeutic range | ### Why Aspirin at High Doses? - At **low doses**: First-order kinetics (t½ ≈ 2–3 hours) - At **high doses** (>1 g): Salicylate conjugation becomes saturated - Result: **Constant elimination rate** regardless of plasma concentration - t½ increases to **15–30 hours** at high doses **Clinical Pearl:** This saturation explains why aspirin toxicity risk increases nonlinearly with dose—elimination cannot keep pace. **High-Yield:** "**Aspirin switches from 1st to 0th order at high doses**"