Capecitabine is a prodrug that is selectively tumour-activated to its cytotoxic moiety, fluorouracil, by thymidine phosphorylase, an enzyme found in higher concentrations in many tumors compared to normal tissues or plasma. Fluorouracil is further metabolized to two active metabolites, 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP), within normal and tumour cells. These metabolites cause cell injury by two different mechanisms. First, FdUMP and the folate cofactor, N5-10-methylenetetrahydrofolate, bind to thymidylate synthase (TS) to form a covalently bound ternary complex. This binding inhibits the formation of thymidylate from 2'-deaxyuridylate. Thymidylate is the necessary precursor of thymidine triphosphate, which is essential for the synthesis of DNA, therefore a deficiency of this compound can inhibit cell division. Secondly, nuclear transcriptional enzymes can mistakenly incorporate FUTP in place of uridine triphosphate (UTP) during the synthesis of RNA. This metabolic error can interfere with RNA processing and protein synthesis through the production of fraudulent RNA.
Capecitabine is a fluoropyrimidine carbamate with antineoplastic activity indicated for the treatment of metastatic breast cancer and colon cancer. It is an orally administered systemic prodrug that has little pharmacologic activity until it is converted to fluorouracil by enzymes that are expressed in higher concentrations in many tumors. Fluorouracil it then metabolized both normal and tumor cells to 5-fluoro-2_-deoxyuridine 5_-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP).
Metabolized by thymidine phosphorylase to fluoruracil.
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