Pharmacology
First-Pass Metabolism
Definition
First-pass metabolism (also called the first-pass effect or presystemic metabolism) is the phenomenon by which an orally administered substance is extensively metabolized by the liver and gut wall before reaching systemic circulation, significantly reducing its bioavailability. Peptides are particularly susceptible to first-pass metabolism due to the abundance of proteolytic enzymes in the gastrointestinal tract and hepatic tissue. This is why most research peptides are administered via parenteral routes (subcutaneous, intravenous, or intranasal) to bypass first-pass degradation and achieve effective systemic concentrations.