If clearance increases with volume of distribution constant, what happens to half-life?

• A. Increase
• B. Remain the same
• C. Decrease
• D. Become zero

Answer: (C)

Half-life in first-order pharmacokinetics is determined by the balance between distribution and clearance: t1/2 = 0.693 × Vd / CL. If the volume of distribution is held constant and clearance increases, the denominator gets larger while the numerator stays the same, so the ratio shrinks. That means it takes less time for the drug concentration to fall by half, so the half-life decreases. For example, doubling clearance with the same Vd halves the half-life. This relationship assumes linear kinetics, where clearance is constant at the given concentrations. The result is not an increase or zero, but a shorter half-life.