Substance
ID:976
Names and Identifiers
Brand Name
Xeloda
IUPAC name
pentyl N-{1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl}carbamate
Synonyms
R340capecitabineCapecitabine
IUPAC Traditional name
capecitabine
Properties
Physical Property
Hydrophobicity(logP)
0.4
Solubility
26 mg/mL
Molecule Details
Drug Groups
approved; investigational
Description
Capecitabine is an orally-administered chemotherapeutic agent used in the treatment of metastatic breast and colorectal cancers. Capecitabine is a prodrug, that is enzymatically converted to fluorouracil (antimetabolite) in the tumor, where it inhibits DNA synthesis and slows growth of tumor tissue.
Indication
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.
Pharmacology
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).
Affected Organisms
Humans and other mammals
Biotransformation
Metabolized by thymidine phosphorylase to fluoruracil.
Absorption
Readily absorbed through the GI tract (~70%)
Half Life
45-60 minutes for capecitabine and its metabolites.
Protein Binding
< 60% (mainly albumin)
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.
References
•
Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44.
[Pubmed]
•
Wagstaff AJ, Ibbotson T, Goa KL: Capecitabine: a review of its pharmacology and therapeutic efficacy in the management of advanced breast cancer. Drugs. 2003;63(2):217-36.
[Pubmed]
•
Koukourakis GV, Kouloulias V, Koukourakis MJ, Zacharias GA, Zabatis H, Kouvaris J: Efficacy of the oral fluorouracil pro-drug capecitabine in cancer treatment: a review. Molecules. 2008 Aug 27;13(8):1897-922.
[Pubmed]
•
Twelves C: Vision of the future: capecitabine. Oncologist. 2001;6 Suppl 4:35-9.
[Pubmed]
•
Milano G, Ferrero JM, Francois E: Comparative pharmacology of oral fluoropyrimidines: a focus on pharmacokinetics, pharmacodynamics and pharmacomodulation. Br J Cancer. 2004 Aug 16;91(4):613-7.
[Pubmed]
•
de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59.
[Pubmed]
External Links
Molecular Spectra
No Data Available
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References
• Koukourakis GV, Kouloulias V, Koukourakis MJ, Zacharias GA, Zabatis H, Kouvaris J: Efficacy of the oral fluorouracil pro-drug capecitabine in cancer treatment: a review. Molecules. 2008 Aug 27;13(8):1897-922. Pubmed
• Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44. Pubmed
• Twelves C: Vision of the future: capecitabine. Oncologist. 2001;6 Suppl 4:35-9. Pubmed
• Wagstaff AJ, Ibbotson T, Goa KL: Capecitabine: a review of its pharmacology and therapeutic efficacy in the management of advanced breast cancer. Drugs. 2003;63(2):217-36. Pubmed
• Milano G, Ferrero JM, Francois E: Comparative pharmacology of oral fluoropyrimidines: a focus on pharmacokinetics, pharmacodynamics and pharmacomodulation. Br J Cancer. 2004 Aug 16;91(4):613-7. Pubmed
• de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. Pubmed