Why does zero-order elimination lead to accumulation with increasing dose?

• A. Because elimination rate increases with concentration
• B. Because elimination rate is fixed and does not depend on concentration
• C. Because volume of distribution decreases with dose
• D. Because clearance doubles with dose

Answer: (B)

When elimination is zero-order, the body removes a fixed amount of drug per unit time, regardless of how much is present. This happens because the metabolic or excretory pathways are saturated, so increasing the drug concentration does not speed up its removal. As a result, higher doses introduce more drug into the body than the saturated system can clear in the same time window. With repeated dosing, the fixed elimination rate cannot keep up, so drug builds up in the body and steady-state concentrations rise, leading to accumulation. The other ideas imply that the elimination rate would change with concentration or depend on something like volume of distribution or a changing clearance, which isn’t the case in zero-order kinetics.