Concepts
Non-clinical sciences/Pharmacology principles · Pharmacokinetics

First-order vs zero-order kinetics

What it means

First-order: elimination rate proportional to concentration → constant half-life (most drugs). Zero-order: a fixed amount eliminated per unit time (enzymes saturated) → no constant half-life; small dose increases cause disproportionate level rises. Zero-order drugs: phenytoin, ethanol, high-dose aspirin/salicylates.

Worked example

A small phenytoin dose increase causes a large, sometimes toxic, level rise because elimination is saturable (zero-order).

In the exam

A patient becomes toxic after a modest dose increase of an antiepileptic whose elimination is saturable, so plasma levels rise disproportionately.

What settles it

Zero-order = saturable, disproportionate level rises (phenytoin/ethanol/aspirin); first-order = proportional, predictable half-life.

Classically confused with

Clearance, half-life & steady state

Source: StatPearls