First-pass extraction can occur in which locations?

• A. Only in the liver
• B. Only in the gut wall
• C. Both gut wall and liver
• D. In neither; first-pass occurs in the lungs

Answer: (C)

First-pass extraction refers to metabolism that occurs before a drug reaches systemic circulation. For orally administered drugs, this can happen in both the gut wall and the liver. The intestinal lining contains enzymes and transporters that can metabolize or limit absorption of the drug as it passes into the portal circulation. The portal vein then delivers the drug to the liver, where hepatic enzymes further metabolize it before it enters the general circulation. Some drugs are substantially metabolized in the gut wall, some mainly in the liver, and many experience significant metabolism in both sites, reducing the amount that reaches systemic circulation.

The lungs aren’t a typical site for first-pass with oral dosing, although pulmonary metabolism can occur for drugs delivered by inhalation.