| Revision as of 18:48, 9 January 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 458863483 of page Tegafur for the Chem/Drugbox validation project (updated: 'ChEMBL'). |
Latest revision as of 12:45, 8 December 2023 edit Entranced98 (talk | contribs)Extended confirmed users, Pending changes reviewers, Rollbackers173,140 edits Adding local short description: "Chemical compound", overriding Wikidata description "group of stereoisomers"Tag: Shortdesc helper |
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{{Short description|Chemical compound}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
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{{Drugbox |
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{{Drugbox |
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| Verifiedfields = changed |
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| Watchedfields = changed |
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| verifiedrevid = 409976519 |
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| verifiedrevid = 470478587 |
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| IUPAC_name = (''RS'')-5-fluoro-1-(tetrahydrofuran-2-yl)pyrimidine-2,4(1''H'',3''H'')-dione |
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| IUPAC_name = (''RS'')-5-Fluoro-1-(tetrahydrofuran-2-yl)pyrimidine-2,4(1''H'',3''H'')-dione |
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| image = Tegafur.png |
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| width = 100 |
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| image = Tegafur.svg |
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| alt = Skeletal formula of tegafur |
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| width = 150 |
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| image2 = Tegafur-3D-balls.png |
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| image2 = Tegafur-3D-balls.png |
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| alt2 = Ball-and-stick model of the tegafur molecule |
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| width2 = 100 |
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| width2 = 125 |
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<!--Clinical data--> |
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<!--Clinical data--> |
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| tradename = |
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| tradename = |
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| Drugs.com = {{drugs.com|international|tegafur}} |
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| Drugs.com = {{drugs.com|international|tegafur}} |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_AU = D |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| pregnancy_category = |
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| pregnancy_category = |
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| licence_EU = yes |
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| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> |
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| legal_AU = S4 |
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| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C --> |
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| legal_UK = POM |
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
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| legal_status = Rx-only |
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| routes_of_administration = Oral |
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| routes_of_administration = Oral |
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<!--Pharmacokinetic data--> |
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<!--Pharmacokinetic data--> |
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| bioavailability = |
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| bioavailability = |
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| protein_bound = |
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| protein_bound = |
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| metabolism = |
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| metabolism = |
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| elimination_half-life = |
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| elimination_half-life = 3.9-11 hours |
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| excretion = |
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| excretion = |
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<!--Identifiers--> |
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<!--Identifiers--> |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 17902-23-7 |
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| CAS_number = 17902-23-7 |
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| ATC_prefix = L01 |
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| ATC_prefix = L01 |
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| ATC_suffix = BC03 |
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| ATC_suffix = BC03 |
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| ATC_supplemental = |
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| ATC_supplemental = {{ATC|L01|BC53}} |
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| PubChem = 288216 |
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| PubChem = 288216 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = |
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| DrugBank = DB09256 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 254191 |
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| ChemSpiderID = 254191 |
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| KEGG = D01244 |
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| KEGG = D01244 |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = 235993 |
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| ChEMBL = 20883 |
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<!--Chemical data--> |
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| chemical_formula = |
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| chemical_formula = |
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| C=8 | H=9 | F=1 | N=2 | O=3 |
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| C=8 | H=9 | F=1 | N=2 | O=3 |
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| molecular_weight = 200.16 g/mol |
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| smiles = FC=1C(=O)NC(=O)N(C=1)2OCCC2 |
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| smiles = FC=1C(=O)NC(=O)N(C=1)2OCCC2 |
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| InChI = 1/C8H9FN2O3/c9-5-4-11(6-2-1-3-14-6)8(13)10-7(5)12/h4,6H,1-3H2,(H,10,12,13)/t6-/m1/s1 |
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| InChIKey = WFWLQNSHRPWKFK-ZCFIWIBFBD |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C8H9FN2O3/c9-5-4-11(6-2-1-3-14-6)8(13)10-7(5)12/h4,6H,1-3H2,(H,10,12,13)/t6-/m1/s1 |
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| StdInChI = 1S/C8H9FN2O3/c9-5-4-11(6-2-1-3-14-6)8(13)10-7(5)12/h4,6H,1-3H2,(H,10,12,13)/t6-/m1/s1 |
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| synonyms = <small>5-fluoro-1-(oxolan-2-yl)pyrimidine-2,4-dione</small> |
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| synonyms = <small>5-fluoro-1-(oxolan-2-yl)pyrimidine-2,4-dione</small> |
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}} |
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}} |
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<!-- Definition and medical uses --> |
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'''Tegafur''' is a ] ] of ] (5-FU) used in the treatment of cancers. It is a component of the combination drug ]. When metabolised, it becomes 5-FU.<ref>{{cite journal | vauthors = El Sayed YM, Sadée W | title = Metabolic activation of R,S-1-(tetrahydro-2-furanyl)-5-fluorouracil (ftorafur) to 5-fluorouracil by soluble enzymes | journal = Cancer Research | volume = 43 | issue = 9 | pages = 4039–4044 | date = September 1983 | pmid = 6409396 }}</ref> |
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<!-- Society and culture --> |
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It was patented in 1967 and approved for medical use in 1972.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=511 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA511 |language=en}}</ref> |
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==Medical uses== |
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As a prodrug to 5-FU it is used in the treatment of the following cancers:<ref name = MD>{{cite web|title=Martindale: The Complete Drug Reference |publisher=Pharmaceutical Press |date=14 November 2011 |access-date=12 February 2014 |url= http://www.medicinescomplete.com/mc/martindale/current/1866-m.htm| veditors = Sweetman S }}</ref> |
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* ] (when combined with ]) |
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* ] (with uracil) |
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* ] |
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* ] (specifically adenocarcinoma, typically with uracil) |
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* ] (usually when combined with gimeracil and oteracil) |
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* ] |
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* ] (with uracil)<ref>{{cite journal | vauthors = Ishikawa T | title = Chemotherapy with enteric-coated tegafur/uracil for advanced hepatocellular carcinoma | journal = World Journal of Gastroenterology | volume = 14 | issue = 18 | pages = 2797–2801 | date = May 2008 | pmid = 18473401 | pmc = 2710718 | doi = 10.3748/wjg.14.2797 | doi-access = free }}</ref> |
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* ] |
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It is often given in combination with drugs that alter its bioavailability and toxicity such as gimeracil, oteracil or uracil.<ref name = MD/> These agents achieve this by inhibiting the enzyme ] (uracil/gimeracil) or ] (oteracil).<ref name = MD/> |
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==Adverse effects== |
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The major side effects of tegafur are similar to fluorouracil and include myelosuppression, central neurotoxicity and gastrointestinal toxicity (especially diarrhoea).<ref name = MD/> Gastrointestinal toxicity is the dose-limiting side effect of tegafur.<ref name = MD/> Central neurotoxicity is more common with tegafur than with fluorouracil.<ref name = MD/> |
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===Pharmacogenetics=== |
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The ] (DPD) enzyme is responsible for the detoxifying metabolism of fluoropyrimidines, a class of drugs that includes ], ], and tegafur.<ref name="pmid23988873">{{cite journal | vauthors = Caudle KE, Thorn CF, Klein TE, Swen JJ, McLeod HL, Diasio RB, Schwab M | title = Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing | journal = Clinical Pharmacology and Therapeutics | volume = 94 | issue = 6 | pages = 640–645 | date = December 2013 | pmid = 23988873 | pmc = 3831181 | doi = 10.1038/clpt.2013.172 }}</ref> ]s within the DPD gene (''DPYD'') can lead to reduced or absent DPD activity, and individuals who are ] or ] for these variations may have partial or complete ]; an estimated 0.2% of individuals have complete ].<ref name="pmid23988873"/><ref name="pmid21919607">{{cite journal | vauthors = Amstutz U, Froehlich TK, Largiadèr CR | title = Dihydropyrimidine dehydrogenase gene as a major predictor of severe 5-fluorouracil toxicity | journal = Pharmacogenomics | volume = 12 | issue = 9 | pages = 1321–1336 | date = September 2011 | pmid = 21919607 | doi = 10.2217/pgs.11.72 }}</ref> Those with partial or complete DPD deficiency have a significantly increased risk of severe or even fatal drug toxicities when treated with fluoropyrimidines; examples of toxicities include ], ] and ].<ref name="pmid23988873"/><ref name="pmid21919607"/> |
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==Mechanism of action== |
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It is a prodrug to 5-FU, which is a ] inhibitor.<ref name = MD/> |
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==Pharmacokinetics== |
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It is metabolised to 5-FU by ].<ref>{{cite journal | vauthors = Nakayama T, Noguchi S | title = Therapeutic usefulness of postoperative adjuvant chemotherapy with Tegafur-Uracil (UFT) in patients with breast cancer: focus on the results of clinical studies in Japan | journal = The Oncologist | volume = 15 | issue = 1 | pages = 26–36 | date = January 2010 | pmid = 20080863 | pmc = 3227888 | doi = 10.1634/theoncologist.2009-0255 }}</ref><ref>{{cite journal | vauthors = Matt P, van Zwieten-Boot B, Calvo Rojas G, Ter Hofstede H, Garcia-Carbonero R, Camarero J, Abadie E, Pignatti F | display-authors = 6 | title = The European Medicines Agency review of Tegafur/Gimeracil/Oteracil (Teysuno™) for the treatment of advanced gastric cancer when given in combination with cisplatin: summary of the Scientific Assessment of the Committee for medicinal products for human use (CHMP) | journal = The Oncologist | volume = 16 | issue = 10 | pages = 1451–1457 | date = October 2011 | pmid = 21963999 | pmc = 3228070 | doi = 10.1634/theoncologist.2011-0224 }}</ref> |
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== Interactive pathway map == |
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{{FluoropyrimidineActivity WP1601|highlight=Tegafur}} |
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== See also == |
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* ] |
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* ] |
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== References == |
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{{reflist}} |
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{{Chemotherapeutic agents}} |
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] |
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] |
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] |
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] |
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] |
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] |
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] |