Which parameter directly determines the fraction of an orally administered dose that reaches systemic circulation?

• A. Volume of distribution
• B. Bioavailability, F
• C. Clearance
• D. Elimination half-life

Answer: (B)

Bioavailability, F, is the fraction of an oral dose that reaches systemic circulation. It captures all losses before the drug enters the blood—absorption from the gut and first-pass metabolism in the gut wall and liver. If absorption is complete and first-pass metabolism is minimal, F approaches 1; if there is incomplete absorption or substantial first-pass loss, F is significantly less than 1. The actual amount entering systemic circulation equals F times the administered dose, and you can relate this to exposure by comparing AUC after oral and IV dosing: F = (AUC_po / AUC_iv) × (Dose_iv / Dose_po). Volume of distribution, clearance, and elimination half-life describe how the drug distributes and is cleared over time, but they do not determine the fraction of the dose that initially reaches systemic circulation.