What is a key assumption of first-order elimination?

• A. Extraction or elimination rate is proportional to concentration and Cl is constant over the therapeutic range.
• B. Clearance changes with concentration.
• C. Half-life varies with dose.
• D. The amount eliminated per unit time is constant.

Answer: (A)

In first-order elimination, the body removes drug at a rate proportional to how much drug is present in the body. That means as the concentration falls, the amount removed per unit time also falls. At the same time, the clearance (the overall efficiency of removal relative to concentration) is treated as constant across the therapeutic range, so the fraction of drug eliminated per unit time stays the same even as concentration changes. Put together, this gives a constant half-life and a rate of elimination that scales with concentration rather than with time or dose.

The statement that reflects this is that the elimination rate is proportional to concentration and clearance remains constant over the therapeutic range. It captures both the proportional relationship and the stable clearance that define first-order kinetics.

Why other ideas don’t fit: if clearance changed with concentration, elimination wouldn’t be first-order. If half-life varied with dose, that points to saturable or non–linear kinetics, not simple first-order. If the amount eliminated per unit time were constant, that would be zero-order elimination, which again doesn’t align with first-order behavior.