If clearance doubles while dose and administration route remain IV, what happens to the AUC?

• A. AUC halves
• B. AUC doubles
• C. AUC remains the same
• D. AUC increases by the square of the factor

Answer: (A)

Exposure to the drug after an IV bolus is governed by how much drug is given and how quickly it is cleared from the body. For an IV bolus, AUC equals Dose divided by Clearance (F = 1 for IV). So if the dose and route stay the same but clearance doubles, AUC becomes Dose divided by twice the original clearance, which is half the original AUC. In other words, increasing clearance reduces systemic exposure proportionally. The AUC would not stay the same, double, or increase by a squared factor under these conditions.