The exit: excretion through the kidney
Excretion is the final removal of drug and its metabolites from the body. The kidney is the chief exit. Blood is filtered at the glomerulus — glomerular filtration passively pushes small, unbound drug into the forming urine — and the tubules can both add more drug by secretion and reclaim some by reabsorption. The net of these three processes is renal clearance. Because the kidney does so much of the work, failing kidneys make many drugs pile up dangerously, which is the whole basis of dose adjustment in renal impairment.
Clearance: the body's cleaning rate
Clearance is the single most important elimination number. It is the volume of plasma completely cleared of drug per unit time — say, litres per hour. Picture it as the size of the body's drain, not the amount drained. Clearance is a fixed property of the patient and drug together (set by liver and kidney function); it does not change just because the dose changes. Crucially, clearance is what determines the steady dose a patient needs: to keep a target concentration, the rate you put drug in must match the rate clearance takes it out.
Half-life and the shape of the decline
Half-life (t½) is the time it takes the plasma concentration to fall by half. It is the number patients and clinicians feel most directly: a short half-life means the drug clears fast and must be dosed often; a long one means it lingers. Half-life is not independent — it emerges from the other two: a drug clears faster (higher clearance) or sits in a smaller space (smaller Vd) the shorter its half-life. The elimination half-life also tells you, in reverse, how long a drug takes to wash out: after about 4–5 half-lives, roughly 97% is gone.
Most drugs eliminate by first-order kinetics: a constant *fraction* leaves per unit time, so a fixed *percentage* (and thus a constant half-life) regardless of how high the level is. But a few drugs — alcohol is the classic example — eliminate by zero-order kinetics: the elimination machinery is saturated, so a constant *amount* leaves per unit time. Once the enzymes are overwhelmed (metabolic saturation), a small dose bump can send levels soaring unpredictably — there is no fixed half-life anymore.
First-order vs zero-order elimination
First-order (constant FRACTION leaves)
100 -> 50 -> 25 -> 12.5 -> 6.25 mg/L
each step = 1 half-life, same % gone
-> half-life is constant
Zero-order (constant AMOUNT leaves)
100 -> 80 -> 60 -> 40 -> 20 mg/L
same 20 mg/L drop each hour (machinery maxed)
-> NO fixed half-life; small dose rise can
overflow the level dangerously