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药品详细

Capecitabine(卡培他滨)

化学结构式图
中文名
卡培他滨
英文名
Capecitabine
分子式
C15H22FN3O6
化学名
pentyl N-{1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl}carbamate
分子量
Average: 359.3501
Monoisotopic: 359.149263656
CAS号
154361-50-9
ATC分类
L01B 抗代谢药
药物类型
small molecule
阶段
approved
商品名
Xeloda;
同义名
capecitabine;R340;
基本介绍

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.

生产厂家
  • Hoffmann la roche inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Walko CM, Lindley C: Capecitabine: a review. Clin Ther. 2005 Jan;27(1):23-44. Pubmed
  2. 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
  3. 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
  4. Twelves C: Vision of the future: capecitabine. Oncologist. 2001;6 Suppl 4:35-9. Pubmed
  5. 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
  6. de Bono JS, Twelves CJ: The oral fluorinated pyrimidines. Invest New Drugs. 2001;19(1):41-59. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Glycerol and Derivatives
  • Carbamates and Derivatives
  • Pyrimidines and Derivatives
Substructures
  • Glycerol and Derivatives
  • Hydroxy Compounds
  • Carbamates and Derivatives
  • Ethers
  • Pyrimidines and Derivatives
  • Alcohols and Polyols
  • Heterocyclic compounds
  • Aromatic compounds
  • Furans
  • Cyanamides
  • Aryl Halides
适应症
Cancer 癌症;
药理
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.
Pharmacodynamics 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).
Mechanism of action 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.
Absorption Readily absorbed through the GI tract (~70%)
Volume of distribution Not Available
Protein binding < 60% (mainly albumin)
Metabolism
Metabolized by thymidine phosphorylase to fluoruracil.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Capecitabine
fluorouracil Details
Capecitabine
    		5’-Deoxy-5-fluorouridine Details
    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.
    Clearance Not Available
    Toxicity Not Available
    Affected organisms
    • Humans and other mammals
    Pathways
    Pathway Name SMPDB ID
    Smp00469 Capecitabine Pathway SMP00469
    理化性质
    Properties
    State solid
    Experimental Properties
    Property Value Source
    melting point 110-121 °C Not Available
    water solubility 26 mg/mL Not Available
    logP 0.4 Not Available
    Predicted Properties
    Property Value Source
    water solubility 2.48e-01 g/l ALOGPS
    logP 1.17 ALOGPS
    logP 0.77 ChemAxon
    logS -3.2 ALOGPS
    pKa (strongest acidic) 8.23 ChemAxon
    pKa (strongest basic) -3.6 ChemAxon
    physiological charge 0 ChemAxon
    hydrogen acceptor count 6 ChemAxon
    hydrogen donor count 3 ChemAxon
    polar surface area 120.69 ChemAxon
    rotatable bond count 7 ChemAxon
    refractivity 82.75 ChemAxon
    polarizability 35.81 ChemAxon
    药物相互作用
    Drug Interaction
    Acenocoumarol Capecitabine may increase the anticoagulant effect of acenocoumarol by increasing its serum concentration.
    Anisindione Capecitabine may increase the anticoagulant effect of anisindione by increasing its serum concentration.
    Dicumarol Capecitabine may increase the anticoagulant effect of dicumarol by increasing its serum concentration.
    Ethotoin Capecitabine increases the effect of hydantoin
    Fosphenytoin Capecitabine increases the effect of hydantoin
    Mephenytoin Capecitabine increases the effect of hydantoin
    Phenytoin Capecitabine increases the effect of hydantoin
    Tamoxifen Capecitabine may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Capecitabine is initiated, discontinued or dose changed.
    Tolbutamide Capecitabine, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Tolbutamide, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in Tolbutamide therapeutic and adverse effects if Capecitabine is initiated, discontinued or dose changed.
    Torasemide Capecitabine, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Capecitabine is initiated, discontinued or dose changed.
    Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
    Trimethoprim The strong CYP2C9 inhibitor, Capecitabine, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Capecitabine is initiated, discontinued or dose changed.
    Voriconazole Capecitabine, a strong CYP2C9 inhibitor, may increase the serum concentration of voriconazole by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of voriconazole if capecitabine is initiated, discontinued or dose changed.
    Warfarin Capecitabine may increase the serum concentration of warfarin by decreasing its metabolism. Monitor for changes in prothrombin time and therapeutic effects of warfarin if capecitabine is initiated or discontinued. Subsequent cycles of capecitabine may increase this effect.
    Zafirlukast Capecitabine, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if capecitabine is initiated, discontinued or dose changed.
    食物相互作用
    • Take 12 hours apart, within 30 minutes of the end of breakfast and dinner to reduce nausea.

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