| 词条 | Tegafur |
| 释义 |
| Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 470478587 | IUPAC_name = (RS)-5-Fluoro-1-(tetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione | image = Tegafur.svg | alt = Skeletal formula of tegafur | width = 150 | image2 = Tegafur-3D-balls.png | alt2 = Ball-and-stick model of the tegafur molecule | width2 = 125 | tradename = | Drugs.com = {{drugs.com|international|tegafur}} | pregnancy_AU = D | pregnancy_US = | pregnancy_category = | licence_EU = yes | legal_AU = S4 | legal_CA = | legal_UK = POM | legal_US = | routes_of_administration = Oral | bioavailability = | protein_bound = | metabolism = | elimination_half-life = 3.9-11 hours | excretion = | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 17902-23-7 | ATC_prefix = L01 | ATC_suffix = BC03 | ATC_supplemental = | PubChem = 288216 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = | 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_formula = | C=8 | H=9 | F=1 | N=2 | O=3 | molecular_weight = 200.16 g/mol | 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 = 5-fluoro-1-(oxolan-2-yl)pyrimidine-2,4-dione }}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.[1] It was patented in 1967 and approved for medical use in 1972.[2] Medical usesAs a prodrug to 5-FU it is used in the treatment of the following cancers:[3]
It is often given in combination with drugs that alter its bioavailability and toxicity such as gimeracil, oteracil or uracil.[3] These agents achieve this by inhibiting the enzyme dihydropyrimidine dehydrogenase (uracil/gimeracil) or orotate phosphoribosyltransferase (oteracil).[3] Adverse effectsThe major side effects of tegafur are similar to fluorouracil and include myelosuppression, central neurotoxicity and gastrointestinal toxicity (especially diarrhoea).[3] Gastrointestinal toxicity is the dose-limiting side effect of tegafur.[3] Central neurotoxicity is more common with tegafur than with fluorouracil.[3] PharmacogeneticsThe dihydropyrimidine dehydrogenase (DPD) enzyme is responsible for the detoxifying metabolism of fluoropyrimidines, a class of drugs that includes 5-fluorouracil, capecitabine, and tegafur.[5] 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.[5][6] 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.[5][6] Mechanism of actionIt is a prodrug to 5-FU, which is a thymidylate synthase inhibitor.[3] PharmacokineticsIt is metabolised to 5-FU by CYP2A6.[7][8] Interactive pathway map{{FluoropyrimidineActivity WP1601|highlight=Tegafur}}See also
References1. ^{{cite journal | pmid = 6409396 | year = 1983 | last1 = El Sayed | first1 = YM | last2 = Sadée | first2 = W | title = Metabolic activation of R,S-1-(tetrahydro-2-furanyl)-5-fluorouracil (ftorafur) to 5-fluorouracil by soluble enzymes | volume = 43 | issue = 9 | pages = 4039–44 | journal = Cancer Research}} {{Chemotherapeutic agents}}2. ^{{cite book |last1=Fischer |first1=Jnos |last2=Ganellin |first2=C. Robin |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=511 |url=https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA511 |language=en}} 3. ^1 2 3 4 5 6 {{cite web|title=Martindale: The Complete Drug Reference|publisher=Pharmaceutical Press|date=14 November 2011|accessdate=12 February 2014|url=http://www.medicinescomplete.com/mc/martindale/current/1866-m.htm|editor=Sweetman, S}} 4. ^{{cite journal|last=Ishikawa|first=T|title=Chemotherapy with enteric-coated tegafur/uracil for advanced hepatocellular carcinoma.|journal=World Journal of Gastroenterology|date=14 May 2008|volume=14|issue=18|pages=2797–2801|doi=10.3748/wjg.14.2797|pmid=18473401|pmc=2710718}} 5. ^1 2 {{cite journal|last1=Caudle|first1=KE|last2=Thorn|first2=CF|last3=Klein|first3=TE|last4=Swen|first4=JJ|last5=McLeod|first5=HL|last6=Diasio|first6=RB|last7=Schwab|first7=M|title=Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing.|journal=Clinical Pharmacology and Therapeutics|date=December 2013|volume=94|issue=6|pages=640–5|doi=10.1038/clpt.2013.172|pmid=23988873|pmc=3831181}} 6. ^1 {{cite journal|last1=Amstutz|first1=U|last2=Froehlich|first2=TK|last3=Largiadèr|first3=CR|title=Dihydropyrimidine dehydrogenase gene as a major predictor of severe 5-fluorouracil toxicity.|journal=Pharmacogenomics|date=September 2011|volume=12|issue=9|pages=1321–36|pmid=21919607|doi=10.2217/pgs.11.72}} 7. ^{{cite journal|last=Nakayama|first=T|author2=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|date=January 2010|volume=15|issue=1|pages=26–36|doi=10.1634/theoncologist.2009-0255|pmid=20080863|pmc=3227888}} 8. ^{{cite journal|vauthors = Matt P, van Zwieten-Boot B, Calvo Rojas G, Ter Hofstede H, Garcia-Carbonero R, Camarero J, Abadie E, Pignatti F |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|date=October 2011|volume=16|issue=10|pages=1451–1457|doi=10.1634/theoncologist.2011-0224|pmid=21963999|pmc=3228070}} 6 : Organofluorides|Prodrugs|Pyrimidinediones|Pyrimidine antagonists|Tetrahydrofurans|Fluoropyrimidines |
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