First-pass metabolism primarily involves metabolism by which organ?

• A. Liver
• B. Kidneys
• C. Liver tissue
• D. Brain

Answer: (A)

First-pass metabolism mainly occurs in the liver. After an oral drug is absorbed from the gut, it travels via the hepatic portal vein to the liver, where hepatocytes with metabolic enzymes (notably cytochrome P450 systems) rapidly transform the drug before it reaches systemic circulation. This hepatic gatekeeping often lowers the amount of unchanged drug that becomes available in the bloodstream, which is why oral bioavailability can be reduced. The kidneys handle excretion rather than the initial metabolism, and the brain is not involved in first-pass processing. Saying “liver tissue” is essentially describing the same organ, but the standard term is the liver.