How is bioavailability F determined, and what role does AUC play in this determination?

• A. F is the fraction reaching systemic circulation; determined by comparing AUCs after IV and oral dosing: F = (AUC_oral × Dose_iv) / (AUC_iv × Dose_oral)
• B. F is the ratio of Dose_oral to Dose_iv.
• C. F is the ratio of AUC_iv to AUC_oral.
• D. F is always equal to 1 for any route.

Answer: (A)

Bioavailability F is the fraction of the administered dose that reaches systemic circulation intact. To determine F, compare the drug’s systemic exposure after oral dosing to that after intravenous dosing, while correcting for the different doses. Since AUC is proportional to the amount that enters circulation (and inversely related to clearance), the relationship is F = (AUC_oral × Dose_iv) / (AUC_iv × Dose_oral). This means IV administration, by definition, has F ≈ 1 (ignoring minor distribution factors), while oral F is reduced by incomplete absorption and first-pass metabolism. AUC captures the total systemic exposure, so a smaller AUC_oral compared to AUC_iv (after adjusting for dose) indicates less drug reaching the bloodstream, hence lower bioavailability.