Which statement is true about first-pass metabolism?

Which statement is true about first-pass metabolism?

• A. It occurs when drugs absorbed from the GI tract pass through the liver before reaching systemic circulation.
• B. It occurs only with intravenous administration.
• C. It increases the amount of drug reaching systemic circulation.
• D. It occurs in the lungs.

Answer: (A)

First-pass metabolism is the process by which a drug absorbed from the gastrointestinal tract is carried via the portal vein to the liver, where it is metabolized before reaching systemic circulation. This hepatic (and sometimes intestinal wall) metabolism reduces the amount of unchanged drug that enters the blood, lowering the drug’s bioavailability. That’s why the statement is true: after oral absorption, the drug must first pass through the liver, which can significantly diminish how much active drug reaches the rest of the body.

This concept is different from administration routes that bypass the liver. Intravenous delivery goes directly into systemic circulation, avoiding the first-pass effect. Because metabolism during first pass lowers the initial amount of active drug, some drugs have much lower oral bioavailability and require higher oral doses or alternative routes. For example, morphine has substantial first-pass metabolism, giving it low oral bioavailability, while nitroglycerin is often given sublingually to bypass first-pass metabolism entirely. The idea that first-pass metabolism occurs in the lungs is not correct; its primary site is the liver (and to some extent the gut wall).