Fluorouracil

Fluorouracil is a fluorinated pyrimidine and acts as an antimetabolite antineoplastic agent. It differs from the naturally occurring product, uracil, by the addition of a fluoride at position 5. Fluorouracil is a component of chemotherapy regimens for many solid tumors, including breast, colorectal, gastrointestinal, and head and neck cancers. The clinical pharmacology of Fluorouracil is complex and the pharmacokinetics are complicated by intra- and inter-patient variability, nonlinear elimination, and erratic bioavailability. The toxicities and efficacy of Fluorouracil differ depending upon the route of administration of the drug.

Fluorouracil‘s innovator is Sanofi Aventis-Global and is known world-wide by the brand names: Carac, REPROTOX® (IV) and Efudex (Valeant North America).

Fluorouracil is a pyrimidine antimetabolite that inhibits thymidylate synthase (TS) and also interferes with RNA synthesis and function. Fluorouracil also has some effects on DNA and causes cytotoxity.

Fluorouracil’s effects:

• RNA-related effects: Formation of fluorouracil monophosphate (FUMP) occurs through two different pathways. FUMP may be formed as the result of direct transfer of a ribose sugar from phosphoribosylpyrophosphate (PPRP) to Fluorouracil via orotic acid phosphoribosyltransferase (OPRTase). In the second pathway, a ribose sugar is added to Fluorouracil by uridine phosphorylase forming fluorouridine (FUrd). FUrd undergoes phosphorylation by uridine kinase to form fluorouracil monophosphate (FUMP). Flurouridine diphosphate (FUDP) and flurouridine triphosphate (FUTP) are formed due to the sequential activity of pyrimidine monophosphate kinase and pyrimidine diphosphate kinase on FUMP. The FUTP is then incorporated into RNA and inhibits RNA activity and synthesis.
  
• DNA-related effects: Fluorouracil can be converted to fluorodeoxyuridine (FdUrd) by thymidine phosphorylase and then fluorodeoxyuridine monophosphate (FdUMP) by thymidine kinase. As a secondary pathway, FdUMP may be formed indirectly by the conversion of FUDP to fluorodeoxyuridine diphosphate (FdUDP) and then to FdUMP. FdUMP forms a tight, but reversible, covalent bond with thymidylate synthase (TS) in the presence of methylenetetrahydrofolate (CH2-THF), a natural reduced folate. Binding of FdUMP to TS inhibits the formation of thymidylate from uracil. Thymidylate is the necessary precursor of thymidine triphosphate (dTTP), one of four deoxyribonucleotides required for synthesis of DNA. Thus, a deficiency of thymidylate leads to depletion of dTTP. Both FdUMP and FdUDP may be converted to fluorodeoxyuridine (FdUTP), which can be incorporated into DNA by DNA polymerase in place of dTTP. When given in combination with leucovorin, the DNA-effects of Fluorouracil are enhanced through stabilization of the ternary complex of TS, FdUMP, and CH2-THF.

Fluorouracil appears in the following formulation and dosage:
Injectable: Per patient weight
Topical Cream: 0.5% and 5%
Capsule: 250 mg

General data on Fluorouracil Active Pharmaceutical Ingredient

CAS Registry: 51-21-8
ATC: L01BC02
Molecular Formula: C4H3FN2O2
Molecular Weight: 130.1
Pharmacopoeias: In Chin., Eur., Int., Jpn, and US.

Ph. Eur. 5.5: Fluorouracil is a white or almost white, crystalline powder. Fluorouracil is sparingly soluble in water; slightly soluble in alcohol. A 1% solution in water has a pH of 4.5 to 5.0.

USP 30: Fluorouracil is a white to practically white, practically odourless, crystalline powder. Fluorouracil is sparingly soluble in water; slightly soluble in alcohol; practically insoluble in chloroform and in ether. 

TAPI's Fluorouracil Pharmaceutical Ingredient

TAPI's Fluorouracil Active Pharmaceutical Ingredient is produced in TAPI Puerto Rico site in Humacao, Puerto Rico.

Fluorouracil is produced by TAPI by Organic synthesis and considered to be high volume Active Pharmaceutical Ingredient.

Other products, in the group of ANTINEOPLASTIC AGENTS - Miscellaneous antineoplastics derivatives available on TAPI's portfolio are:  Bicalutamide,Bortezomib,Etoposide,Fludarabine_Phosphate and Pemetrexed Diacid.Contact us today for information on these products.

2008 Available DMF: U.S. DMF and CEP.

TAPI provide full service on Fluorouracil and other APIs in our portfolio. Our local sales offices provide full information on our product, regulatory compliance and documentation on Fluorouracil. Contact us today for further inquiries and samples and kilograms availability information for TAPI's Fluorouracil.

Legal Note

Product exploitation, including development, sales and offer for sale are performed where permissible by patent law. This presentation is not and should not constitute an offer for sale in territories where it is not permitted by law. In USA Products  that  Currently on Patent are available for R&D Use in Accordance with 35 USC §271 (e) (1).

*TAPI stands for Teva's Active Pharmaceutical Ingredients