Definition
Description
Top Gene Interactions
Related Pathways
General Information
- Metabolism: Metabolized by thymidine phosphorylase to fluoruracil. Route of Elimination: Capecitabine and its metabolites are predominantly excreted in urine; 95.5% of administered capecitabine dose is recovered in urine. Fecal excretion is minimal (2.6%). The major metabolite excreted in urine is FBAL which represents 57% of the administered dose.About 3% of the administered dose is excreted in urine as unchanged drug. Half Life: 45-60 minutes for capecitabine and its metabolites.
- Uses/Sources: For the treatment of patients with metastatic breast cancer resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen. May also be used in combination with docetaxel for the treatment of metastatic breast cancer in patients who have failed to respond to, or recurred or relasped during or following anthracycline-containing chemotherapy. Capecitabine is used alone as an adjuvant therapy following the complete resection of primary tumor in patients with stage III colon cancer when monotherapy with fluroprymidine is preferred. The use or capecitabine in combination regimens for advanced gastric cancer is currently being investigated.
- Route of Exposure: Readily absorbed through the GI tract (~70%)
Mechanism of Action
Target Name | Mechanism of Action | References |
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DNA RNA |
9264308 18979208 9807659 15032669 12724731 15763604 |
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Thymidylate synthase Dihydropyrimidine dehydrogenase [NADP(+)] |
Capecitabine is a prodrug that is selectively tumour-activated to its cytotoxic moiety, fluorouracil, by thymidine phosphorylase. Fluorouracil is further metabolized to two active metabolites, 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP), within normal and tumour cells. FdUMP inhibits DNA synthesis by reducing normal thymidine production, while FUTP inhibits RNA and protein synthesis by competing with uridine triphosphate.3 The active moiety of capecitabine, fluorouracil, is cell cycle phase-specific (Sphase). Both normal and tumor cells metabolize 5-FU to 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). 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, so that a deficiency of this compound can inhibit cell division. Second 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. |
15134221 12527930 16926630 15132128 15866500 12866042 12481438 15709193 11587492 11291832 |
Capecitabine Interacts with Diseases
Disease | Inference Score | References/Inference Genes |
Breast carcinoma | 15.39 |
|
Stomach Neoplasms | 15.18 |
|
Esophageal squamous cell carcinoma | 13.65 |
|
Prostatic Neoplasms | 12.93 |
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Liver Cirrhosis, Experimental | 12.47 |
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Pancreatic carcinoma | 12.46 |
|
Hepatocellular carcinoma | 12.14 |
|
Adrenal Gland Neoplasms | 11.76 |
|
Nasopharyngeal carcinoma | 11.12 |
|
Tongue Neoplasms | 10.93 |
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Adenocarcinoma | 10.45 |
|
Diabetes Complications | 9.68 |
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Squamous cell carcinoma | 9.64 |
|
Lung Neoplasms | 9.63 |
|
Neoplasm Recurrence, Local | 9.43 |
|
Glioblastoma multiforme | 8.88 |
|
Head and Neck Neoplasms | 8.5 |
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Osteosarcoma | 7.97 |
|
Adenocarcinoma Of Esophagus | 7.91 |
|
Hypoxia-Ischemia, Brain | 7.89 |
|