førstepassasjemetabolisme

First-pass metabolism, also known as presystemic metabolism, refers to the initial biotransformation of an orally administered drug. When a drug is ingested, it is absorbed from the gastrointestinal tract and enters the portal vein. This vein carries blood directly to the liver before it circulates throughout the rest of the body. The liver is a primary site for drug metabolism, containing a high concentration of enzymes, particularly the cytochrome P450 (CYP) superfamily.

As the drug passes through the liver, these enzymes can significantly alter its chemical structure. This metabolic process can inactivate the drug, convert it into active metabolites, or even produce toxic compounds. Consequently, only a fraction of the original dose may reach the systemic circulation in an unchanged form. This fraction is known as the oral bioavailability.

The extent of first-pass metabolism varies greatly among different drugs. Some drugs undergo extensive hepatic metabolism, resulting in very low oral bioavailability. This necessitates higher oral doses or alternative routes of administration, such as intravenous, intramuscular, or transdermal, which bypass the liver and enter the systemic circulation directly. Conversely, drugs with minimal first-pass metabolism have higher oral bioavailability and can be administered in lower doses orally. Understanding first-pass metabolism is crucial for determining appropriate drug dosages and optimizing therapeutic outcomes.