clearance

Clearance is the body's drug-disposal rate, expressed in an unusual but powerful way: as the volume of plasma that is completely scrubbed free of drug per unit time (for example, litres per hour). It does not say how much drug is removed; it says how big a pool of plasma is fully cleaned each minute. Picture a swimming-pool filter rated by the litres of water it can fully purify per hour, regardless of how dirty the water is.

Total (systemic) clearance is the sum of clearances by all eliminating organs — chiefly hepatic clearance by the liver and renal clearance by the kidneys, plus any minor routes. It is the single most important parameter for chronic dosing, because at steady state the maintenance dosing rate must equal clearance times the target concentration.

Crucially, for most drugs clearance is a constant property of the body independent of concentration (first-order behaviour) — it does not change when you double the dose. Half-life, by contrast, depends on both clearance and volume of distribution, so two drugs with the same half-life can have very different clearances. Disease that damages the liver or kidneys lowers clearance and demands dose reduction.