Learning Objective (Step 1)
Differentiate zero-order vs first-order drug elimination, recognize the examples of each, and understand the implications for toxicity, dosing, and therapeutic monitoring.
Drug elimination refers to the removal of a drug from the body, primarily via metabolism and excretion. It can follow zero-order or first-order kinetics, which determines how drug concentration changes over time.
Zero-Order Elimination
Definition:
- The drug is eliminated at a constant amount per unit time, regardless of plasma concentration (Cp).
- Plasma concentration decreases linearly over time.
Key Features:
| Feature | Details |
|---|---|
| Rate of elimination | Constant (mg/hr), independent of Cp |
| Plasma concentration (Cp) | Decreases linearly |
| Kinetics type | Capacity-limited elimination |
| Mnemonic | PEA → Phenytoin, Ethanol, Aspirin (high/toxic doses) |
| Shape | “0” in zero-order → linear slope (not exponential) |
Clinical Relevance:
- Toxicity can develop quickly if the dose exceeds the metabolic capacity.
First-Order Elimination
Definition:
- Drug is eliminated at a rate proportional to its plasma concentration (i.e., a constant fraction per unit time).
- Plasma concentration decreases exponentially over time.
Key Features:
| Feature | Details |
|---|---|
| Rate of elimination | Proportional to Cp (mg/hr, depending on Cp) |
| Plasma concentration (Cp) | Decreases exponentially |
| Kinetics type | Most drugs in therapeutic doses |
| Shape | Curved exponential decay on a graph. |
| Clinical relevance | Predictable dosing and steady-state calculations |
Quick Comparison Table
| Feature | Zero-Order | First-Order |
|---|---|---|
| Elimination rate | Constant (same amount/time) | Proportional to Cp (same fraction/time) |
| Cp vs time | Linear decrease | Exponential decrease |
| Capacity | Saturable/limited | Usually unsaturated |
| Examples | Phenytoin, Ethanol, Aspirin (toxic) | Most drugs |
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