Tegafur/uracil
Tegafur/uracil Uses, Dosage, Side Effects, Food Interaction and all others data.
Tegafur/uracil is an anti-tumor compound containing tegafur (1-(2-tetrahydrofuryl)-5-fluorouracil) and uracil in a molar ratio of 1:4. It was developed as an anti-cancer therapy by Taiho Pharmaceutical Co Ltd. It is approved in different countries but it is not yet approved by the FDA, Health Canada or EMA.
The use of the combination of tegafur and uracil allows increasing the oral bioavailability, improving the pharmacokinetic behavior of the delivered 5-fluoruracil and increasing the half-life of tegafur. The effect of this combo drug can ameliorate the usage by reducing the dosage frequency which tends to be uncomfortable for the patients. The effect of tegafur's metabolites results in a decreased thymidine synthesis, DNA synthesis, disrupted RNA function and tumor cell cytotoxicity.
| Trade Name | Tegafur/uracil |
| Generic | Tegafur-uracil |
| Tegafur-uracil Other Names | Tegafur/uracil, UFUR |
| Type | |
| Formula | C12H13FN4O5 |
| Weight | Average: 312.257 Monoisotopic: 312.086997698 |
| Protein binding | The serum binding protein of tegafur is of 52% while the protein binding of uracil is negligible. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Tegafur/uracil is indicated for the first line treatment of metastatic colorectal cancer with concomitant administration of calcium folinate. Colorectal cancer is the third most diagnosed cancer and 30% of the cases can present the metastatic state.
How Tegafur/uracil works
The generation of this combo was conceived under the reported activation by the transformation of tegafur to 5-fluorouracil. These findings have convened with results that suggested that the degradation of 5-fluorouracil can be depressed by the addition of uracil. Uracil competitively inhibits the catabolic action of dihydropyrimidine dehydrogenase. This combined activity allows a significant increase in blood and tissue 5-fluorouracil levels by inhibiting its first-pass hepatic metabolism. The active metabolites of tegafur inhibit the enzyme thymidylate synthase (5-fluoro-deoxyuridine-monophosphate) and intercalate into RNA (5-fluorouridine-triphosphate).
Toxicity
High doses of tegafur are reported to present unique central nervous system toxicity. The oral administration of tegafur has been reported to present toxicity but the usage of the combo product tegafur/uracil have presented higher levels of 5-fluorouracil without the toxic effects or oral tegafur.
Volume of Distribution
The volume of distribution of tegafur is reported to be 59 L while the uracil volume of distribution of 474 L.
Elimination Route
The absorption into systemic circulation is very rapid and the peak concentration is reached within 1-2 hours. After a single dose of tegafur/uracil of 300 mg/m2/day in three divided doses, tegafur plasma concentration of >1000 ng/ml are maintained throughout the 8-hour dosing interval, whereas uracil concentrations decline rapidly following the peak concentration. The plasma concentration of 5-fluorouracil peaks at 30-60 min after administration with 200 ng/ml and remain detectable for 8-hour dosing interval. There is no significant long-term accumulation of either uracil, tegafur or 5-fluorouracil.
Half Life
The presence of uracil generates an increase in the half-life of tegafur and it is registered to be of 11 hours. The elimination half-life of uracil is of 20-40 minutes.
Clearance
The reported clearance of tegafur when administered in the form of tegafur/uracil ranged from 47 to 175 ml/min
Elimination Route
Less than 20% of the administered dose of tegafur is excreted intact in the urine following the oral administration.
Innovators Monograph
You find simplified version here Tegafur/uracil
