Tìm theo
Gemcitabine
Các tên gọi khác (7 ) :
  • 2'-Deoxy-2',2'-difluorocytidine
  • 2',2'-Difluorodeoxycytidine
  • 4-amino-1-((2R,4R,5R)-3,3-Difluoro-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)pyrimidin-2(1H)-one
  • Gemcitabin
  • Gemcitabina
  • Gemcitabine
  • Gemcitabinum
Thuốc chống ung thư và tác động vào hệ thống miễn dịch
Thuốc Gốc
Small Molecule
CAS: 95058-81-4
ATC: L01BC05
ĐG : Eli Lilly & Co. , http://www.lilly.com
CTHH: C9H11F2N3O4
PTK: 263.1981
Gemcitabine is a nucleoside analog used as chemotherapy. It is marketed as Gemzar® by Eli Lilly and Company. As with fluorouracil and other analogues of pyrimidines, the drug replaces one of the building blocks of nucleic acids, in this case cytidine, during DNA replication. The process arrests tumor growth, as new nucleosides cannot be attached to the "faulty" nucleoside, resulting in apoptosis (cellular "suicide"). Gemcitabine is used in various carcinomas: non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer. It is being investigated for use in oesophageal cancer, and is used experimentally in lymphomas and various other tumor types.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C9H11F2N3O4
Phân tử khối
263.1981
Monoisotopic mass
263.071762265
InChI
InChI=1S/C9H11F2N3O4/c10-9(11)6(16)4(3-15)18-7(9)14-2-1-5(12)13-8(14)17/h1-2,4,6-7,15-16H,3H2,(H2,12,13,17)/t4-,6-,7-/m1/s1
InChI Key
InChIKey=SDUQYLNIPVEERB-QPPQHZFASA-N
IUPAC Name
4-amino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one
Traditional IUPAC Name
gemcitabine
SMILES
NC1=NC(=O)N(C=C1)[C@@H]1O[C@H](CO)[C@@H](O)C1(F)F
Độ tan chảy
168.64 °C
Độ hòa tan
Soluble
logP
-1.4
logS
-1.1
pKa (strongest acidic)
11.52
pKa (Strongest Basic)
-1.3
PSA
108.38 Å2
Refractivity
53.25 m3·mol-1
Polarizability
21.45 Å3
Rotatable Bond Count
2
H Bond Acceptor Count
6
H Bond Donor Count
3
Physiological Charge
0
Number of Rings
2
Bioavailability
1
Rule of Five
true
pKa
3.6
Dược Lực Học : Gemcitabine is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (or DNA synthesis phase of the cell cycle), stopping normal development and division. Gemcitabine blocks an enzyme which converts the cytosine nucleotide into the deoxy derivative. In addition, DNA synthesis is further inhibited because Gemcitabine blocks the incorporation of the thymidine nucleotide into the DNA strand. It demonstrates dose-dependent synergistic activity with cisplatin in vitro. In vivo, gemcitabine showed activity in combination with cisplatin against the LX-1 and CALU-6 human lung xenografts, but minimal activity was seen with the NCI-H460 or NCI-H520 xenografts. Gemcitabine was synergistic with cisplatin in the Lewis lung murine xenograft. Sequential exposure to gemcitabine 4 hours before cisplatin produced the greatest interaction.
Cơ Chế Tác Dụng : Gemcitabine is a nucleoside analog used as chemotherapy. It is marketed as Gemzar® by Eli Lilly and Company. As with fluorouracil and other analogues of pyrimidines, the drug replaces one of the building blocks of nucleic acids, in this case cytidine, during DNA replication. The process arrests tumor growth, as new nucleosides cannot be attached to the "faulty" nucleoside, resulting in apoptosis (cellular "suicide"). Gemcitabine is used in various carcinomas: non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer. It is being investigated for use in oesophageal cancer, and is used experimentally in lymphomas and various other tumor types. Gemcitabine inhibits thymidylate synthetase, leading to inhibition of DNA synthesis and cell death. Gemcitabine is a prodrug so activity occurs as a result of intracellular conversion to two active metabolites, gemcitabine diphosphate and gemcitabine triphosphate by deoxycitidine kinase. Gemcitabine diphosphate also inhibits ribonucleotide reductase, the enzyme responsible for catalyzing synthesis of deoxynucleoside triphosphates required for DNA synthesis. Finally, Gemcitabine triphosphate (diflurorodeoxycytidine triphosphate) competes with endogenous deoxynucleoside triphosphates for incorporation into DNA.
Dược Động Học :
▧ Absorption :
The pharmacokinetics of gemcitabine are described by a 2-compartment model.
▧ Volume of Distribution :
* 50 L/m^2 [infusions lasting <70 minutes] * 370 L/m^2 [long infusions]
▧ Protein binding :
Plasma protein binding is negligible (<10%)
▧ Metabolism :
Transformed via nucleoside kinases to two active metabolites, gemcitabine diphosphate and gemcitabine triphosphate. Can also undergo deamination via cytidine deaminase to an inactive uracil metabolite (dFdU).
▧ Route of Elimination :
Within one (1) week, 92% to 98% of the dose was recovered, almost entirely in the urine. Gemcitabine (<10%) and the inactive uracil metabolite, 2´-deoxy-2´,2´-difluorouridine (dFdU), accounted for 99% of the excreted dose.
▧ Half Life :
Gemcitabine half-life for short infusions ranged from 42 to 94 minutes, and the value for long infusions varied from 245 to 638 minutes, depending on age and gender, reflecting a greatly increased volume of distribution with longer infusions.
▧ Clearance :
* 92.2 L/hr/m2 [Men 29 yrs] * 75.7 L/hr/m2 [Men 45 yrs] * 55.1 L/hr/m2 [Men 65 yrs] * 40.7 L/hr/m2 [Men 79 yrs] * 69.4 L/hr/m2 [Women 29 yrs] * 57 L/hr/m2 [Women 45 yrs] * 41.5 L/hr/m2 [Women 65 yrs] * 30.7 L/hr/m2 [Women 79 yrs]
Độc Tính : Myelosuppression, paresthesias, and severe rash were the principal toxicities, LD50=500 mg/kg (orally in mice and rats)
Chỉ Định : Gemcitabine is indicated for the treatment of advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy; metastatic ovarian cancer; inoperable, locally advanced (Stage IIIA or IIIB), or metastatic (Stage IV) non-small cell lung cancer; and locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas.
Tương Tác Thuốc :
  • Acenocoumarol Gemcitabine may increase the anticoagulant effect of acenocoumarol.
  • Anisindione Gemcitabine may increase the anticoagulant effect of anisindione.
  • Bivalirudin Gemcitabine may enhance the adverse/toxic effect of Bleomycin. The risk of pulmonary toxicity may be increased. Use extreme caution if using gemcitabine and bleomycin in combination. Monitor for the development of pulmonary toxicity.
  • Dicoumarol Gemcitabine may increase the anticoagulant effect of dicumarol.
  • Paclitaxel Paclitaxel increases the effect/toxicity of gemcitabine
  • Temsirolimus Co-administration of Temsirolimus and Gemcitabine may result in serious adverse drug reactions.
  • Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
  • Warfarin Gemcitabine may increase the anticoagulant effect of warfarin.
Liều Lượng & Cách Dùng : Injection, powder, lyophilized, for solution - Intravenous - 200 mg, 1 g, 2 g
Solution - Intravenous - 200 mg/5.26 mL; 1 g/26.3 mL; 2 g/52.6 mL
Dữ Kiện Thương Mại
Giá thị trường
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    Sản phẩm biệt dược : Gemcired
  • Công ty : Fresenius
    Sản phẩm biệt dược : Gemita
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    Sản phẩm biệt dược : Gemzar
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Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00441
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=60750
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506425
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07650
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D02368
ChemSpider
http://www.chemspider.com/Chemical-Structure.54753.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0002-7501-01
PharmGKB
http://www.pharmgkb.org/drug/PA449748
Wikipedia
http://en.wikipedia.org/wiki/Gemcitabine
RxList
http://www.rxlist.com/cgi/generic/gemcitab.htm
Drugs.com
http://www.drugs.com/cdi/gemcitabine.html
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