Tegafur

200.17

200.17

241-846-2

DTXSID8021305

L01BC53|L - Antineoplastic and immunomodulating agents

2934999090

58.6

-0.3

white to off-white Very Fine Crystalline Powder

1.51 g/cm³

171-173 °C

1.557

Partly miscible in water.DMSO: >50mg/mL

2-8°C

6.1

UN 2811 6.1/PG 2

3

23/24/25

22-36/37/39-45

YR0450000

T

Stable under normal temperatures and pressures.

P261-P280-P301 + P310-P311

H301-H311-H331

|Danger|H301 (95.12%): Toxic if swallowed [Danger Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P310, P302+P352, P304+P340, P311, P312, P321, P322, P330, P361, P363, P403+P233, P405, and P501|Aggregated GHS information provided by 41 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Oral LD50 value in rat, mouse and dog are 930mg/kg, 775mg/kg, and 34mg/kg, respectively [MSDS]. Continuous exposure to tegafur may cause physical defects in the developing embryo (teratogenesis). Acute toxicity from the combination use of tegafur was associated with nausea, vomiting, diarrhoea, mucositis, gastrointestinal irritation, bleeding, bone marrow depression, and respiratory failure. Overdose may lead to fatal complications. In case of overdose, appropriate therapeutic and supportive medical interventions should be implemented.

Tegafur is 52.3% bound to serum proteins and 5-FU is 18.4% protein bound.

Indicated for the treatment of cancer usually in combination with other biochemically modulating drugs. Indicated in adults for the treatment of advanced gastric cancer when given in combination with [DB00515]. Indicated for the first-line treatment of metastatic colorectal cancer with [DB03419] and calcium folinate.|Teysuno is indicated in adults for the treatment of advanced gastric cancer when given in combination with cisplatin.

Tegafur is an antineoplastic agent that belongs in the class of pyrimidine analogues. It interferes with the 2'-deoxythymidylate (DTMP) synthesis in the pyrimidine pathway, resulting in inhibition of DNA synthesis. In a phase III trial investigating the clinical efficacy of S-1 (tegafur/gimeracil/oteracil) in patients with advanced or recurrent gastric cancer, treatment resulted in a high response rate and was associated with a longer overall survival and longer progression-free survival rate when used in combination with cisplatin. In a meta analysis, triple combination therapy consisting of tegafur, gimeracil and oteracil showed longer survival times and well tolerance in patients with advanced gastric cancer. Tegafur and its active metabolites are potent myleosuppressive agents.

Antimetabolites that are useful in cancer chemotherapy. (See all compounds classified as Antimetabolites, Antineoplastic.)

Tegafur displays a dose-proportional pharmacokinetic properties. Tegafur is rapidly and well absorbed into the systemic circulation, reaching the peak plasma concentration within 1 to 2 hours of administration.|Following oral administration, about less 20% of total tegafur is excreted unchanged in the urine.|The volume of distribution based on apparent volume of distribution and urinary excretion data of tegafur is 16 L/m^2.|No pharmacokinetic data available.

Hepatic CYP2A6 is the predominant enzyme that mediates 5-hydroxylation of tegafur to generate 5'-hydroxytegafur. This metabolite is unstable and undergoes spontaneous degradation to form 5-FU, which is an active antineoplastic agent that exerts a pharmacological action on tumours. 5-FU is rapidly metabolised by the liver enzyme dihydropyrimidine dehydrogenase (DPD).|Tegafur has known human metabolites that include 5-Fluorouracil.

The elimination half life of tegafur is approximately 11 hours.

The transformation of 2'-deoxyurindylate (dUMP) to 2'-deoxythymidylate (dTMP) is essential in driving the synthesis of DNA and purines in cells. Thymidylate synthase catalyzes the conversion of dUMP to dTMP, which is a precursor of thymidine triphosphate (TTP), one of the four deoxyribonucleotides required for DNA synthesis. After administration into the body, tegafur is converted into the active antineoplastic metabolite, fluorouracil (5-FU). In tumour cells, 5-FU undergoes phosphorylation to form the active anabolites, including 5-fluorodeoxyuridine monophosphate (FdUMP). FdUMP and reduced folate are bound to thymidylate synthase leading to formation of a ternary complex which inhibits DNA synthesis. In addition, 5-fluorouridine-triphosphate (FUTP) is incorporated into RNA causing disruption of RNA functions.

1-(2-Tetrahydrofuryl)-5-fluorouracil

2,4(1H,3H)-Pyrimidinedione, 5-fluoro-1-(tetrahydro-2-furanyl)-: INACTIVE

Human drugs -> Teysuno -> EMA Drug Category|Antineoplastic agents -> Human pharmacotherapeutic group|Human drugs -> Rare disease (orphan)