{{Short description|Chemical compound}} {{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 470478587 | IUPAC_name = (''RS'')-5-Fluoro-1-(tetrahydrofuran-2-yl)pyrimidine-2,4(1''H'',3''H'')-dione | image = Tegafur.svg | image_class = skin-invert-image | alt = Skeletal formula of tegafur | width = 150 | image2 = Tegafur-3D-balls.png | image_class2 = bg-transparent | alt2 = Ball-and-stick model of the tegafur molecule | width2 = 125 <!--Clinical data--> | tradename = | Drugs.com = {{drugs.com|international|tegafur}} | pregnancy_AU = D | pregnancy_US = <!-- A / B / C / D / X --> | pregnancy_category = | licence_EU = yes | legal_AU = S4 | legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII --> | legal_UK = POM | legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> | routes_of_administration = Oral <!--Pharmacokinetic data--> | bioavailability = | protein_bound = | metabolism = | elimination_half-life = 3.9-11 hours | excretion = <!--Identifiers--> | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 17902-23-7 | ATC_prefix = L01 | ATC_suffix = BC03 | ATC_supplemental = {{ATC|L01|BC53}}
| PubChem = 288216 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB09256 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 254191 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 1548R74NSZ | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D01244 | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 20883 <!--Chemical data--> | chemical_formula = | C=8 | H=9 | F=1 | N=2 | O=3 | smiles = FC=1C(=O)NC(=O)N(C=1)[C@@H]2OCCC2 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | 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 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = WFWLQNSHRPWKFK-ZCFIWIBFSA-N | synonyms = <small>5-fluoro-1-(oxolan-2-yl)pyrimidine-2,4-dione</small> }} <!-- Definition and medical uses --> '''Tegafur''' is a chemotherapeutic prodrug of 5-fluorouracil (5-FU) used in the treatment of cancers. It is a component of the combination drug tegafur/uracil. 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>
<!-- Society and culture --> 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>
==Medical uses== 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> * Stomach (when combined with gimeracil and oteracil) * Breast (with uracil) * Gallbladder * Lung (specifically adenocarcinoma, typically with uracil) * Colorectal (usually when combined with gimeracil and oteracil) * Head and neck * Liver (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> * Pancreatic
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 dihydropyrimidine dehydrogenase (uracil/gimeracil) or orotate phosphoribosyltransferase (oteracil).<ref name = MD/>
==Adverse effects== 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/>
===Pharmacogenetics===
The dihydropyrimidine dehydrogenase (DPD) enzyme is responsible for the detoxifying metabolism of fluoropyrimidines, a class of drugs that includes 5-fluorouracil, capecitabine, 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> Genetic variations within the DPD gene (''DPYD'') can lead to reduced or absent DPD activity, and individuals who are heterozygous or homozygous for these variations may have partial or complete DPD deficiency; an estimated 0.2% of individuals have complete DPD deficiency.<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 myelosuppression, neurotoxicity and hand-foot syndrome.<ref name="pmid23988873"/><ref name="pmid21919607"/>
==Mechanism of action== It is a prodrug to 5-FU, which is a thymidylate synthase inhibitor.<ref name = MD/>
==Pharmacokinetics== It is metabolised to 5-FU by CYP2A6.<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>
== Interactive pathway map == {{FluoropyrimidineActivity WP1601|highlight=Tegafur}}
== See also == * Tegafur/uracil * Tegafur/gimeracil/oteracil
== References == {{reflist}}
{{Chemotherapeutic agents}}
Category:Organofluorides Category:Prodrugs Category:Uracil derivatives Category:Pyrimidine antagonists Category:Tetrahydrofurans Category:Fluoropyrimidines Category:Drugs in the Soviet Union