first-pass effect

The first-pass effect, also known as first-pass metabolism, refers to the initial metabolism of a drug by the body. This process occurs when a drug is administered orally and is absorbed from the gastrointestinal tract into the portal circulation. Before reaching the systemic circulation and its target site, the drug passes through the liver, where it undergoes metabolic alteration. This can significantly reduce the amount of active drug that reaches the bloodstream, affecting its overall potency and effectiveness.1

Drugs are absorbed into the bloodstream and distributed throughout the body. However, drugs that are highly lipid-soluble are rapidly absorbed and can quickly reach most tissues, including the brain. These drugs are also more likely to be metabolized in the liver and reabsorbed in the kidneys, potentially reducing their excretion. Some drugs bind to plasma proteins, which can act as a reservoir and maintain the drug's level in the blood.12