U01.05.008 Elimination of drugs

Understanding drug elimination kinetics is critical for USMLE Step 1 preparation. The two primary types of elimination processes—Zero-Order and First-Order—are differentiated by how the drug is cleared from the body.

Zero-Order Elimination

In zero-order elimination, the rate of elimination is constant, regardless of the concentration of the drug (Cp). A fixed amount of drug is eliminated per unit time. This leads to a linear decline in drug concentration over time.

Key Features:
- The rate of elimination is constant.
- Drug concentration (Cp) decreases linearly over time.
- Common in capacity-limited elimination.
- Occurs when the metabolic system is saturated (high drug concentrations).
Examples of Drugs with Zero-Order Elimination:
- Phenytoin (at high doses)
- Ethanol
- Aspirin (at high or toxic concentrations)
Mnemonic to Remember:
- PEA (Phenytoin, Ethanol, Aspirin) — The letter P in “PEA” is round like the 0 in zero-order elimination.

First-Order Elimination

In contrast, first-order elimination involves a rate of drug clearance that is proportional to its concentration. This means that a constant fraction of the drug is eliminated per unit time. As a result, the drug concentration (Cp) decreases exponentially over time.

Key Features:
- Rate of elimination is proportional to the drug concentration.
- Drug concentration (Cp) decreases exponentially with time.
- Applies to most drugs under typical therapeutic conditions.
- Common in flow-dependent elimination.
Examples of Drugs with First-Order Elimination:
- Most drugs (e.g., antibiotics, statins, etc.)

Comparison of Zero-Order and First-Order Elimination

Characteristic	Zero-Order Elimination	First-Order Elimination
Rate of Elimination	Constant amount eliminated per unit time	Constant fraction eliminated per unit time
Concentration-Time Curve	Linear decline in drug concentration	Exponential decline in drug concentration
Dependency	Capacity-limited (saturation of enzymes)	Flow-dependent (dependent on concentration)
Examples	Phenytoin, Ethanol, Aspirin (high/toxic doses)	Most therapeutic drugs (e.g., antibiotics, statins)

Points to Remember

Zero-order elimination is rare and usually occurs when the body’s capacity to metabolize the drug is overwhelmed.
First-order elimination is the most common form of drug elimination and applies to most drugs.
The rate of drug elimination in zero-order is independent of concentration, while in first-order, it depends on the concentration.
For zero-order drugs, always consider whether the drug concentration is toxic or at a saturation point.

USMLE Step 1 Review Series

Curriculum

U01.05.008 Elimination of drugs

Zero-Order Elimination

First-Order Elimination

Comparison of Zero-Order and First-Order Elimination

Points to Remember

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