Pharmacokinetics: First-Order and Zero-Order Elimination

Drug Elimination

• Drugs with first-order elimination have a constant half-life of elimination, regardless of the amount of drug in the body.
• The concentration of a first-order elimination drug in the blood decreases by 50% for every half-life.
• Most drugs in clinical use demonstrate first-order kinetics.
• Zero-order elimination involves a constant rate of elimination, regardless of concentration.
• Zero-order elimination drugs do not have a constant half-life, and their concentrations in plasma decrease in a linear fashion over time.

Pharmacokinetic Models

• A two-compartment model is used to simulate the distribution and elimination phases of a drug.
• The two compartments consist of the blood and the extravascular tissues.
• Each phase has a characteristic half-life: 1/2a for the first phase, and 1/2β for the second phase.
• When concentration is plotted on a logarithmic axis, the elimination phase for a first-order drug is a straight line.

Distribution Models

• Some drugs behave as if they were distributed to only 1 compartment (e.g., if they are restricted to the vascular compartment).
• Others have more complex distributions that require more than 2 compartments for accurate mathematical models.

Drug Development and Regulation

• The sale and use of drugs are regulated in almost all countries by governmental agencies, such as the FDA in the United States.
• New drugs are developed in industrial or academic laboratories, and must undergo a series of animal and experimental human studies (clinical trials) before being approved for therapeutic use.
• New drugs can emerge from a variety of sources, including the identification of a new target for a disease.