zero-order kinetics
Zero-order kinetics describes elimination at a fixed flat rate: a constant amount of drug is removed per unit time, no matter how much is present. Think of a factory machine that can process exactly 100 widgets an hour — pile up 500 or 5,000 in front of it and it still clears only 100 per hour. The bottleneck, not the supply, sets the pace.
This happens when the eliminating enzymes or transporters become saturated — fully occupied and working at maximum capacity. The plasma concentration then falls in a straight line rather than an exponential curve, and there is no single constant half-life: the apparent half-life lengthens as the concentration rises. Doubling the dose can more than double the resulting blood level, which is dangerous.
Only a handful of common drugs show zero-order behaviour at therapeutic doses, and they are precisely the ones to respect: ethanol (the classic example, cleared at a roughly fixed grams-per-hour rate), phenytoin, and high-dose aspirin. For these, small dose increases can tip the patient from therapeutic into toxic concentrations with little warning.
Phenytoin shifts from first- to zero-order kinetics within its therapeutic range, so a modest dose rise can cause a sharp, unexpected jump in blood level and toxicity — a key reason it is monitored.
Saturation makes phenytoin levels jump unpredictably.
Zero-order: constant amount per time, no fixed half-life, straight-line (not exponential) decline, and disproportionate jumps in level with dose. Ethanol and phenytoin are the textbook cases.