A drug exhibits zero-order elimination. Which of the following best describes its concentration-time profile and a clinical consequence?

• A. The concentration decreases exponentially with time; dosing remains easily scalable.
• B. The amount decreases with a variable rate; small dose increases have little effect.
• C. The amount decreases linearly with time at a constant rate; small increases in dose can cause disproportionately large concentrations due to nonlinearity.
• D. The concentration remains constant regardless of dose.

Answer: (C)

Zero-order elimination means the body removes drug at a constant amount per unit time, independent of how much drug is present. Because the elimination rate is fixed, the amount in the body declines in a straight line over time. If the volume of distribution stays constant, the concentration (amount divided by Vd) also falls roughly linearly with time.

A key clinical consequence is nonlinearity between dose and concentration. Since the elimination rate is capped, small increases in dose can push you into a region where the same fixed amount is cleared per hour, leading to disproportionately larger peak concentrations and longer overall exposure. In short, the amount decreases linearly with time, but the dose–concentration relationship is nonlinear, so modest dose increases can produce much larger concentrations.