Define first-pass metabolism and identify the organ primarily responsible.

• A. The kidney metabolizes many drugs before they reach systemic circulation; first-pass metabolism reduces oral bioavailability.
• B. The liver metabolizes many drugs before they reach systemic circulation; first-pass metabolism reduces oral bioavailability.
• C. The pancreas metabolizes many drugs before they reach systemic circulation; first-pass metabolism reduces oral bioavailability.
• D. The heart metabolizes many drugs before they reach systemic circulation; first-pass metabolism reduces oral bioavailability.

Answer: (B)

First-pass metabolism is the process by which a drug is metabolized before it reaches the rest of the body, most often after oral administration. After you swallow a drug, it is absorbed in the gut and carried via the hepatic portal vein to the liver, where liver enzymes—particularly those in the cytochrome P450 family—convert part of the drug into metabolites. This pre-systemic metabolism decreases the amount of unchanged drug that reaches the bloodstream, lowering oral bioavailability. The liver is the primary organ responsible for this pre-systemic processing; while some metabolism can occur in the gut wall, it’s the liver that does the bulk of first-pass metabolism. Other organs listed (kidneys, pancreas, heart) are not the main sites of first-pass drug metabolism.