Which statement best describes the clinical significance of bioavailability and first-pass metabolism?

• A. Bioavailability is unaffected by first-pass metabolism.
• B. First-pass metabolism increases the amount of drug reaching systemic circulation.
• C. Bioavailability is the fraction of a drug reaching systemic circulation; first-pass metabolism reduces oral bioavailability, potentially requiring dose adjustments.
• D. First-pass metabolism has no impact on oral dosing strategies.

Answer: (C)