Presystemic extraction: mechanisms and consequences

Journal of Clinical Pharmacology
D J Greenblatt


Many drugs have incomplete systemic availability after oral dosage. This can be attributed to incomplete absorption from the gastrointestinal tract, or to presystemic extraction, in which a fraction of an orally administered dose is biotransformed before reaching the systemic circulation. Presystemic extraction can occur either via biotransformation by gastrointestinal mucosa or enteric flora, or via metabolism during the "first-pass" through the liver. For drugs with low oral bioavailability due to high presystemic extraction, impaired clearance leads to increased peak plasma levels and greater area under the concentration-time curve, but minimal change in elimination half-life.


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