First pass effect

The first-pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation.^[1][2] It is the fraction of drug lost during the process of absorption which is generally related to the liver and gut wall. Notable drugs that experience a significant first-pass effect are imipramine, morphine, propranolol, buprenorphine, diazepam, midazolam, demerol, cimetidine, and lidocaine.

After a drug is swallowed, it is absorbed by the digestive system and enters the hepatic portal system. It is carried through the portal vein into the liver before it reaches the rest of the body. The liver metabolizes many drugs, sometimes to such an extent that only a small amount of active drug emerges from the liver to the rest of the circulatory system. This first pass through the liver thus greatly reduces the bioavailability of the drug.

The four primary systems that affect the first pass effect of a drug are the enzymes of the gastrointestinal lumen, gut wall enzymes, bacterial enzymes, and hepatic enzymes.

In drug design, drug candidates may have good druglikeness but fail on first-pass metabolism, because it is biochemically selective.

Alternative routes of administration like suppository, intravenous, intramuscular, inhalational aerosol, transdermal and sublingual avoid the first-pass effect because they allow drugs to be absorbed directly into the systemic circulation. Note that the intravenous route also avoids the absorption phase.

Drugs with high first pass effect have a considerably higher oral dose than sublingual or parenteral dose. There is marked individual variation in the oral dose due to differences in the extent of first pass metabolism. Oral bioavailability is apparently increased in patients with severe liver diseases like Cirrhosis. It is also increased if another drug competing with it in first pass metabolism given concurrently. Eg. propranolol and chlorpromazine.

See also

• ADME, an acronym in pharmacokinetics and pharmacology standing for absorption, distribution, metabolism, and excretion
• Biopharmaceutics Classification System
• Drug
• Enteral administration
• Partition coefficient

References

External links

• National Library of Medicine, Toxicology Tutor II, Influence of Route of Exposure
• University of Nottingham School of Nursing, Reusable Learning Objects--Understanding First Pass Metabolism