First pass metabolism refers to the phenomenon whereby compounds or drugs, that are absorbed from the gastrointestinal tract, first get metabolized in the intestinal epithelium and the liver before they reach systemic circulation. Our intestinal epithelium, first prevents absorption of certain molecules and also breaks other molecules down with cytochrome P450 enzymes like CYP3A4. What is left, is taken up through the mesenteric venous system to the hepatic portal vein and brought to the liver for hepatic metabolism. Our liver, made up of roughly 240 billion cells, then metabolizes almost everything that gets absorbed in the gastrointestinal tract before either dispersing of it through biliary secretion or releasing it into the systemic circulation. For most drugs or compounds, the first-pass effect is the fraction of drug or compound lost during this process.
Note: the other route of absorption (that does not undergo ‘first-pass metabolism’) occurs via lymphatic absorption where fatty acids, cholesterol, and fat soluble vitamins get emulsified and broken down by bile salts and lipases, absorbed via micelles, repackaged into chylomicrons, and then taken up by the lymphatic system which dumps into the vena cava.
