Tegafur

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Tegafur
Skeletal formula of tegafur
Ball-and-stick model of the tegafur molecule
Systematic (IUPAC) name
(RS)-5-Fluoro-1-(tetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione
Clinical data
AHFS/Drugs.com International Drug Names
Pregnancy
category
  • AU: D
Legal status
Routes of
administration
Oral
Pharmacokinetic data
Biological half-life 3.9-11 hours
Identifiers
CAS Registry Number 17902-23-7 YesY
ATC code L01BC03
PubChem CID: 288216
ChemSpider 254191 YesY
UNII 1548R74NSZ YesY
KEGG D01244 YesY
ChEMBL CHEMBL20883 N
Synonyms 5-fluoro-1-(oxolan-2-yl)pyrimidine-2,4-dione
Chemical data
Formula C8H9FN2O3
Molecular mass 200.16 g/mol
 N (what is this?)  (verify)

Tegafur (INN, BAN, USAN) is a chemotherapeutic fluorouracil prodrug used in the treatment of cancers. It is a component of the combination drug tegafur/uracil. When metabolised, it becomes 5-fluorouracil.[1]

Medical uses[edit]

As a prodrug to 5-FU it is used in the treatment of the following cancers:[2]

It is often given in combination with drugs that alter its bioavailability and toxicity such as gimeracil, oteracil or uracil.[2] These agents achieve this by inhibiting the enzyme dihydropyrimidine dehydrogenase (uracil/gimeracil) or orotate phosphoribosyltransferase (oteracil).[2]

Adverse effects[edit]

The major side effects of tegafur are similar to fluorouracil and include myelosuppression, central neurotoxicity and gastrointestinal toxicity (especially diarrhoea).[2] Gastrointestinal toxicity is the dose-limiting side effect of tegafur.[2] Central neurotoxicity is more common with tegafur than with fluorouracil.[2]

Pharmacogenetics[edit]

The dihydropyrimidine dehydrogenase (DPD) enzyme is responsible for the detoxifying metabolism of fluoropyrimidines, a class of drugs that includes 5-fluorouracil, capecitabine, and tegafur.[4] 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.[4][5] 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.[4][5] The FDA-approved drug labels for fluorouracil and capecitabine state that the drug is contraindicated in patients with known DPD deficiency.[6][7]

Mechanism of action[edit]

It is a prodrug to fluorouracil which is a thymidylate synthase inhibitor.[2]

Pharmacokinetics[edit]

It is metabolised into fluorouracil by CYP2A6.[8][9]


Interactive pathway map[edit]

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

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FluoropyrimidineActivity_WP1601 go to article go to article go to article go to pathway article go to pathway article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to PubChem Compound go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to pathway article go to pathway article go to article go to article go to article go to article go to article go to WikiPathways go to article go to article go to article go to article go to article go to article go to article go to article go to article
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FluoropyrimidineActivity_WP1601 go to article go to article go to article go to pathway article go to pathway article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to PubChem Compound go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to pathway article go to pathway article go to article go to article go to article go to article go to article go to WikiPathways go to article go to article go to article go to article go to article go to article go to article go to article go to article
|{{{bSize}}}px|alt=Fluorouracil (5-FU) Activity edit]]
Fluorouracil (5-FU) Activity edit
  1. ^ The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601". 

See also[edit]

References[edit]

  1. ^ El Sayed, YM; Sadée, W (1983). "Metabolic activation of R,S-1-(tetrahydro-2-furanyl)-5-fluorouracil (ftorafur) to 5-fluorouracil by soluble enzymes". Cancer Research 43 (9): 4039–44. PMID 6409396. 
  2. ^ a b c d e f g Sweetman, S, ed. (14 November 2011). "Martindale: The Complete Drug Reference". Pharmaceutical Press. Retrieved 12 February 2014. 
  3. ^ Ishikawa, T (14 May 2008). "Chemotherapy with enteric-coated tegafur/uracil for advanced hepatocellular carcinoma." (PDF). World Journal of Gastroenterology : WJG 14 (18): 2797–2801. doi:10.3748/wjg.14.2797. PMC 2710718. PMID 18473401. 
  4. ^ a b c Caudle, KE; Thorn, CF; Klein, TE; Swen, JJ; McLeod, HL; Diasio, RB; Schwab, M (December 2013). "Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing.". Clinical pharmacology and therapeutics 94 (6): 640–5. doi:10.1038/clpt.2013.172. PMID 23988873. 
  5. ^ a b Amstutz, U; Froehlich, TK; Largiadèr, CR (September 2011). "Dihydropyrimidine dehydrogenase gene as a major predictor of severe 5-fluorouracil toxicity.". Pharmacogenomics 12 (9): 1321–36. PMID 21919607. 
  6. ^ "ADRUCIL (fluorouracil) injection [Teva Parenteral Medicines, Inc.]". DailyMed. Teva Parenteral Medicines, Inc. August 2012. Retrieved 17 March 2015. 
  7. ^ "XELODA (capecitabine) tablet, film coated [Genentech, Inc.]". DailyMed. Genentech, Inc. December 2013. Retrieved 17 March 2015. 
  8. ^ Nakayama, T; Noguchi, S (January 2010). "Therapeutic usefulness of postoperative adjuvant chemotherapy with Tegafur-Uracil (UFT) in patients with breast cancer: focus on the results of clinical studies in Japan." (PDF). The Oncologist 15 (1): 26–36. doi:10.1634/theoncologist.2009-0255. PMC 3227888. PMID 20080863. 
  9. ^ Matt, P; van Zwieten-Boot, B; Calvo Rojas, G; Ter Hofstede, H; Garcia-Carbonero, R; Camarero, J; Abadie, E; Pignatti, F (October 2011). "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)." (PDF). The Oncologist 16 (10): 1451–1457. doi:10.1634/theoncologist.2011-0224. PMC 3228070. PMID 21963999.