CC15 – First- and zero-order kinetics

CC15. First- and zero-order kinetics refers to changes in the amount of drug in the body as a function of time: Zero order refers to change by a constant amount per unit time, whereas first order refers to change by a constant fraction per unit time.

15.1. Most drugs follow first-order kinetics, which is observed when the rate of change of plasma concentration is proportional to the plasma concentration.

15.2. When the drug is eliminated by first-order kinetics, clearance and half-life are constant.

15.3. Zero-order kinetics is observed when a process is saturated. Saturation occurs when a process is operating at a maximum rate due to all the active sites on an enzyme or transporter protein being occupied.

15.4. Kinetics can change from first order to zero order as the drug concentration increases and elimination mechanisms become saturated.

15.5. First- and zero-order kinetics are mathematical models that can be distinguished graphically: A plot of drug plasma concentration versus time shows simple exponential decay for first-order kinetics and linear decline for zero-order kinetics. A plot of the log concentration versus time shows linear decline for first-order kinetics.