Tegafur

Tegafur

Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy category	AU: D
Routes of administration	Oral
ATC code	L01BC03 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) UK: POM (Prescription only)
Pharmacokinetic data
Biological half-life	3.9-11 hours
Identifiers
IUPAC name (RS)-5-Fluoro-1-(tetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione
Synonyms	5-fluoro-1-(oxolan-2-yl)pyrimidine-2,4-dione
CAS Number	17902-23-7 Y
PubChem CID	288216
ChemSpider	254191 Y
UNII	1548R74NSZ
KEGG	D01244 Y
ChEMBL	CHEMBL20883 N
ECHA InfoCard	100.038.027
Chemical and physical data
Formula	C8H9FN2O3
Molar mass	200.16 g/mol
3D model (Jmol)	Interactive image
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?)

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.

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

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).

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.

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.