U01.05.005 Elimination of drugs

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Learning Objectives

Distinguish between Zero-Order and First-Order Elimination. Understand how plasma concentration ( $C_p$ ) relates to the rate of elimination and identify the key drugs that exhibit capacity-limited kinetics for the USMLE Step 1.

1. Zero-Order Elimination

In zero-order kinetics, the rate of elimination is constant regardless of the plasma concentration. This occurs when the elimination enzymes are saturated.

Feature	Details
Elimination Rate	Constant amount of drug eliminated per unit time (e.g., $2$ U/h).
Plasma Concentration ( $C_p$ )	Decreases linearly with time.
Half-life ( $t_{1/2}$ )	Variable; decreases as $C_p$ decreases.
Classification	Capacity-limited elimination (enzymes are saturated).

Mnemonic (PEA): Phenytoin, Ethanol, and Aspirin (at high/toxic doses) are round like the “0” in zero-order.

2. First-Order Elimination

In first-order kinetics, the rate of elimination is directly proportional to the drug concentration. This applies to most drugs at therapeutic concentrations.

Feature	Details
Elimination Rate	Constant fraction of drug eliminated per unit time.
Plasma Concentration ( $C_p$ )	Decreases exponentially with time.
Half-life ( $t_{1/2}$ )	Constant; independent of $C_p$ .
Classification	Flow-dependent elimination.

3. Comparison Summary

Kinetics Type	Equation Slope	Elimination Rate vs. $C_p$
Zero-Order	Horizontal line (constant rate)	The rate does not change as $C_p$ increases.
First-Order	Linear positive slope	The rate increases linearly as $C_p$ increases.

Activity:

High-Yield Clinical Pearls:

Saturation Risk: Drugs like Phenytoin and Aspirin shift from first-order to zero-order as they saturate their metabolic pathways. This makes them dangerous because a small increase in dose can lead to a massive increase in $C_p$ .
Half-life Consistency: In first-order kinetics, $t_{1/2}$ is constant ( $0.7 \times V_d / CL$ ), meaning it always takes $4$ – $5$ half-lives to clear $95$ % of the drug, regardless of the starting dose.
The $C_p$ vs. Time Graph: On a semi-log plot, first-order elimination appears as a straight line, whereas on a standard linear plot, zero-order elimination is the straight line.