First pass effect - Wikipedia First pass effect Not to be confused with First dose effect. This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. ( December 2016 ) 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. 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 ). 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. 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 Jump up ^ Rowland, Malcolm ( January 1972 ). `` Influence of route of administration on drug availability ''. Journal of Pharmaceutical Sciences. 61 ( 1 ) : 70 -- 74. 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 ) : 1 -- 25. 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 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 This pharmacology - related article is a stub. You can help Wikipedia by expanding it. Retrieved from `` https://en.wikipedia.org/w/index.php?title=First_pass_effect&oldid=811832007 '' Categories : Pharmacokinetics Medicinal chemistry Pharmacology stubs Hidden categories : Articles needing additional references from December 2016 All articles needing additional references All articles lacking reliable references Articles lacking reliable references from December 2016 All stub articles Talk About Wikipedia Čeština Deutsch Eesti فارسی Français Italiano Kurdî Latina Nederlands 日本 語 Polski Português Slovenščina Српски / srpski Srpskohrvatski / српскохрватски Suomi Svenska Türkçe 中文 Edit links This page was last edited on 24 November 2017, at 08 : 06. Text is available under the Creative Commons Attribution - ShareAlike License ; additional terms may apply. By using this site, you agree to the Terms of Use and Privacy Policy. Wikipedia ® is a registered trademark of the Wikimedia Foundation, Inc., a non-profit organization. About Wikipedia

Question: which route of administration is most likely to subject a drug to a first pass effect
Answer: drug is swallowed