First pass metabolism applies to which route of administration?

• A. IV medications only
• B. Subcutaneous medications
• C. PO medications only
• D. Intra-arterial medications

Answer: (C)

First-pass metabolism is the breakdown of a drug by the liver that occurs after the drug is absorbed from the gut and before it reaches systemic circulation. This happens because, when a drug is taken by mouth, it enters the intestinal lining and then travels via the hepatic portal vein directly to the liver, where a portion can be metabolized before the rest of the body sees it. That’s why oral medications often have reduced bioavailability compared to other routes, since a chunk may be inactivated on its first pass through the liver. Other routes—like intravenous, subcutaneous, or intra-arterial—deliver drug into the bloodstream without first going through the liver via the portal system, so they bypass this initial hepatic metabolism. Hence, first-pass metabolism applies to oral administration.