Expansion
First order clears a constant proportion, zero order a constant amount
Expansion
- First order: a constant proportion is eliminated per unit time, so the half life is constant. This applies to most drugs at therapeutic doses
- Zero order (saturation) kinetics: a constant amount is eliminated per unit time, because the metabolising enzymes are saturated. There is no constant half life
The classic zero order drugs, remembered as PEAT:
- P - Phenytoin
- E - Ethanol
- A - Aspirin, in overdose
- T - Theophylline, and heparin at high dose
“A small dose rise gives a large level rise.” With phenytoin an increase from 300 to 350 mg daily can more than double the plasma level, which is why it is titrated in small increments against levels.
Many drugs are first order therapeutically and zero order in overdose, once the enzymes saturate. That is exactly why overdose toxicity is disproportionate to the dose taken, and it applies to both aspirin and paracetamol.
Steady state takes 4 to 5 half lives in first order kinetics whatever the dose, which is the reason a loading dose is used when the effect is needed sooner.