Which statement about zero-order elimination is true?

• A. The elimination rate is proportional to drug concentration.
• B. The half-life remains constant across concentrations.
• C. Clearance is directly proportional to dose.
• D. The elimination rate is constant and independent of concentration.

Answer: (D)

Zero-order elimination means the body removes a fixed amount of drug per unit time, regardless of how much drug is present, at least while concentrations remain high enough for the saturable pathway to be saturated. Because the elimination rate is constant, it does not track changes in concentration, so the rate stays the same even as the drug concentration declines. This also means the concentration falls linearly over time, and the half-life is not the same across different starting concentrations.

Clearance, defined as the elimination rate divided by concentration, will change as concentration changes when the rate is fixed. With a constant rate, clearance effectively increases as concentration falls, and it is not directly proportional to dose. Thus the statement that the elimination rate is constant and independent of concentration is the true one. In contrast, the rate being proportional to concentration, a constant half-life across concentrations, or clearance directly proportional to dose do not describe zero-order elimination.