Which factor increases the AUC after an oral dose if clearance remains constant?

• A. Higher Dose
• B. Higher Clearance
• C. Lower Bioavailability
• D. Faster Elimination

Answer: (A)

Exposure to a drug after an oral dose depends on how much reaches the systemic circulation relative to how quickly it is cleared. For linear pharmacokinetics, AUC after an extravascular dose equals F × Dose divided by CL, where F is bioavailability and CL is clearance. If clearance stays constant and F is unchanged, raising the dose directly increases AUC in a proportional fashion. In other words, more drug entering the body (higher dose) results in greater total exposure (higher AUC). The other factors would either decrease AUC (higher clearance, lower bioavailability, or faster elimination) or only affect exposure if the dose changes, but under constant clearance, increasing dose is the way to boost AUC.