A drug exhibits zero-order kinetics at therapeutic doses. Which statement best describes the relationship between plasma concentration and time for this drug?

## Zero-Order Kinetics: Linear Elimination **Key Point:** Zero-order kinetics (also called **saturation kinetics** or **dose-dependent kinetics**) occurs when the elimination rate is **constant and independent of plasma concentration**. The elimination rate is determined by the maximum capacity of metabolizing enzymes, not by the amount of drug present. ### Characteristic Features of Zero-Order Kinetics | Feature | Zero-Order | First-Order | |---------|-----------|-------------| | **Elimination rate** | Constant (mg/hr) | Proportional to C (concentration-dependent) | | **Plasma concentration vs. time** | Linear (straight line) | Exponential (curved line) | | **Half-life** | Increases with dose | Constant, independent of dose | | **Clearance** | Decreases with dose | Constant, independent of dose | | **Rate equation** | $\frac{dC}{dt} = -k_0$ | $\frac{dC}{dt} = -k_e \times C$ | ### Mathematical Representation For zero-order kinetics: $$C = C_0 - k_0 \times t$$ where: - C = Plasma concentration at time t - C₀ = Initial plasma concentration - k₀ = Zero-order rate constant (mg/hr) - t = Time This is a **linear equation** — the graph is a straight line with a negative slope of −k₀. **High-Yield:** The plasma concentration decreases at a **constant rate** (e.g., 10 mg/L per hour), regardless of whether the initial concentration is 100 mg/L or 50 mg/L. ### Clinical Examples of Zero-Order Kinetics 1. **Ethanol (alcohol)** — metabolized at ~7–10 g/hr regardless of blood alcohol level 2. **Phenytoin** — at therapeutic doses, follows Michaelis-Menten kinetics (saturable) 3. **Aspirin** — at high doses 4. **Theophylline** — at high concentrations **Clinical Pearl:** Zero-order kinetics is dangerous because increasing the dose does not proportionally increase the half-life — the drug accumulates unpredictably. This is why phenytoin toxicity can occur with small dose increases. **Mnemonic:** **"ZERO = Straight line"** — Zero-order kinetics produces a straight line on a concentration-vs.-time graph (linear), while first-order produces a curve (exponential).