3.8 : First Pass Effect

Presystemic elimination, or the first-pass effect, is the metabolism of drugs that reduces their effective concentration at the site of action. Apart from the first-pass effect, the systemic bioavailability of the drug is also reduced by other factors, including incomplete absorption or chemical degradation of drugs.

Depending on the route of administration, drugs can be metabolized in the liver, intestine, lungs, and vasculature. Orally administered drugs are first absorbed through the intestinal wall and then transported to the liver by the mesenteric vessels via the portal veins. Inside the liver, they are metabolized or eliminated into the bile, reducing the availability of the drug reaching the systemic circulation. The oral drug dosage required to produce a therapeutic effect would be higher than the intravenous dose of the same drug. Although higher oral drug dosage can reduce the first-pass effect and provide an adequate response, it also increases the plasma concentration of toxic metabolites, leading to one or more adverse effects. Drug administration via transdermal, parental, sublingual and nasal routes is always preferred to avoid the first-pass effect. Drugs administered by inhalation also bypass the first-pass effect of the liver. However, the lungs can still excrete such drugs through exhalation.