In first-order kinetics, how does the half-life respond to changes in dose?

• A. It increases with higher dose
• B. It remains constant across doses
• C. It decreases with higher dose
• D. It depends on the volume of distribution

Answer: (B)

In first-order kinetics, the half-life is constant across different doses because elimination is proportional to the drug concentration. The half-life t1/2 is determined by the elimination rate constant k (t1/2 ≈ 0.693/k). In linear kinetics, k stays the same when you change the dose, since clearance (CL) and volume of distribution (Vd) are constant and t1/2 = 0.693·Vd/CL. So increasing or decreasing the dose changes how much drug is eliminated per unit time, but not the time it takes for the concentration to fall by half. Only if the elimination pathways saturate (shift toward zero-order kinetics) would the half-life become dose-dependent.