clearance, bioavailability, & the first-pass effect

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When molecules show less than 100% bioavailability, the reduced bioavailability is often explained by something called the first-pass effect. In the first-pass effect, the molecule is absorbed from the gastrointestinal tract to the hepatic portal system, a branch of the circulatory system. The molecule then passes through the liver on the way to general circulation and the plasma. In the liver, a fraction of the molecule is broken down through hepatic clearance. The fraction lost equals EH, and the remaining portion of the molecule is F, the bioavailability. Absorption is rarely an issue for approved drugs because leads with poor absorption are eliminated from consideration.