Which organ is primarily responsible for first pass metabolism?

The liver is primarily responsible for first-pass metabolism, which is a critical pharmacological process. When a drug is ingested orally, it travels through the gastrointestinal tract and is absorbed into the bloodstream. From there, it enters the portal circulation and is transported directly to the liver before it reaches systemic circulation.

During this initial pass through the liver, enzymes metabolize the drug, often reducing its concentration and, in some cases, altering its active form. This process can significantly affect the bioavailability of the medication—meaning the amount of the drug that reaches systemic circulation and is available for therapeutic effect. Consequently, drugs that undergo extensive first-pass metabolism may require higher oral dosages to achieve the desired effect compared to other routes of administration that bypass the liver, such as intravenous administration.

The other options serve different roles in drug processing and metabolism. Kidneys play a crucial role in excreting waste and drugs from the body, lungs are involved in gas exchange and can metabolize certain compounds, and intestines are involved in absorption but are not primarily responsible for first-pass metabolism.