- A process in which a drug administered by mouth is absorbed from the gastrointestinal tract and transported via the portal vein to the liver, where it is metabolized.
- As a result, in some cases only a small proportion of the active drug reaches the systemic circulation and its intended target tissue.
- First-pass metabolism can be bypassed by giving the drug via sublingual e.g. Isosorbide mononitrate or buccal routes.
- The first-pass effect is a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation.
- 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
- Gastrointestinal lumen
- Gut wall enzymes
- Bacterial enzymes
- Hepatic enzymes.
- In drug design, drug candidates may have good drug likeness but fail on first-pass metabolism, because it is biochemically selective.
- 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 increased if another drug competing with it in first pass metabolism given concurrently. Eg. propranolol and chlorpromazine
- Avoid the first-pass effect because they allow drugs to be absorbed directly into the systemic circulation.
- Inhalational aerosol,
- Transdermal and
|LOW||INTERMEDIATE||HIGH-NOT GIVEN ORALLY||HIGH ORAL DOSE|
- A drug administered through Oral route undergo high first pass metabolism
- High first pass metabolism Causes for less bioavailability
- High first pass metabolism is seen in Lignocaine, Propranolol & Salbutamol
- Isosorbide mononitrate passes by first pass metabolism
- Sublingual route escape first pass metabolism
- Theophylline escape first pass metabolism
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