Tegafur

Tegafur

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	AU: S4 (Prescription only) UK: POM (Prescription only)
Routes of administration	Oral
Pharmacokinetic data
Biological half-life	3.9-11 hours
Identifiers
CAS Number	17902-23-7 Y
ATC code	L01BC03 (WHO)
PubChem	CID: 288216
ChemSpider	254191 Y
UNII	1548R74NSZ Y
KEGG	D01244 Y
ChEMBL	CHEMBL20883 N
Synonyms	5-fluoro-1-(oxolan-2-yl)pyrimidine-2,4-dione
Chemical data
Formula	C8H9FN2O3
Molecular mass	200.16 g/mol
SMILES FC=1C(=O)NC(=O)N(C=1)[C@@H]2OCCC2
InChI InChI=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 Y Key:WFWLQNSHRPWKFK-ZCFIWIBFSA-N Y
NY (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.

Medical uses

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

• 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)

• Pancreatic

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

Adverse effects

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

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. 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. 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.

Mechanism of action

It is a prodrug to fluorouracil which is a thymidylate synthase inhibitor.

Pharmacokinetics

It is metabolised into fluorouracil by CYP2A6.

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles.

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|{{{bSize}}}px|alt=Fluorouracil (5-FU) Activity edit]]

File:FluoropyrimidineActivity_WP1601.png

Fluorouracil (5-FU) Activity edit

See also

• Tegafur/uracil
• Tegafur/gimeracil/oteracil