What does oral bioavailability measure and how does first-pass metabolism influence it?

• A. The fraction of an orally administered drug that reaches systemic circulation unchanged; first-pass metabolism reduces it.
• B. The rate of absorption from the GI tract.
• C. The fraction of drug bound to plasma proteins.
• D. The amount of drug excreted unchanged in urine.

Answer: (A)

Oral bioavailability is the fraction of an orally administered dose that reaches the systemic circulation as unchanged drug. First-pass metabolism lowers this value because metabolic processes in the gut wall and liver act on the drug before it reaches the bloodstream. Enzymes in these tissues can convert the drug to metabolites, so even if it is absorbed, only part of the original drug remains unchanged and available to exert effect. This is why a drug can be well absorbed from the gut but still have low oral bioavailability. The other options describe different pharmacokinetic concepts—rate of absorption, plasma protein binding, and renal excretion—not the extent of drug reaching systemic circulation unchanged.