First pass effect

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Not to be confused with First dose effect.

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Illustration showing the hepatic portal vein system.

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,
pethidine, marijuana, cimetidine, lidocaine, and nitroglycerin.

First pass metabolism may occur in the liver (for propranolol, lidocaine,
chloromethiasole and GTN) or in the gut (for benzylpenicillin and insulin).[3]

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.

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 is given concurrently. E.g. propranolol and chlorpromazine.[4]
[unreliable medical source?]

See also[edit]
ADME, an acronym in pharmacokinetics and pharmacology standing for absorption,
distribution, metabolism, and excretion
Biopharmaceutics Classification System
Drug
Enteral administration
Partition coefficient
References[edit]
Jump up ^ Rowland, Malcolm (January 1972). "Influence of route of administration on
drug availability". Journal of Pharmaceutical Sciences. 61 (1): 7074.
doi:10.1002/jps.2600610111. ISSN 0022-3549. PMID 5019220.
Jump up ^ Pond, Susan M.; Tozer, Thomas N. (January 1984). "First-Pass
Elimination". Clinical Pharmacokinetics. 9 (1): 125. doi:10.2165/00003088-
198409010-00001. ISSN 0312-5963. PMID 6362950.
Jump up ^ Bath-Hextall, Fiona (October 16, 2013). "Understanding First Pass
Metabolism". University of Nottingham. Retrieved October 26, 2017.
Jump up ^ "Foods to Increase Metabolism". www.thefitroute.com. Retrieved 28 April
2016.
External links[edit]
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

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