First pass effect

In order for a perorally administered pharmaceutical active ingredient to develop its effects at the site of action, it must usually enter the systemic bloodstream (bioavailability). To do so, it must pass through the intestinal wall, the liver and part of the circulation. Despite complete absorption in the intestine, the bioavailability of a drug can be reduced to a relevant extent, i.e. in the mucous membrane of the small intestine(CYP3A4), in the liver (CYP3A4 and other CYP enzymes) and in the small circulation.

The first-pass metabolism is often referred to the liver. Documented are, however, examples for active agents which are already metabolized in the intestinal mucosa to a relevant extent (e.g. Ciclosporin, Midazolam, Nifedipin and Tacrolimus). S.a.under bioavailability