First pass metabolism occurs primarily in the liver, one of the body's major metabolic organs. When a substance is ingested orally, it travels through the digestive system and is absorbed into the portal vein, which carries blood directly to the liver. Here, enzymes may metabolize the substance extensively, reducing the amount that reaches systemic circulation. This phenomenon can drastically reduce the bioavailability of certain drugs, necessitating higher oral doses or alternative routes of administration.
