Tìm theo
Docetaxel
Các tên gọi khác (4 ) :
  • Docetaxel anhydrous
  • N-Debenzoyl-N-(tert-butoxycarbonyl)-10-deacetylpaclitaxel
  • N-Debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol
  • TXL
Thuốc chống ung thư và tác động vào hệ thống miễn dịch
Thuốc Gốc
Small Molecule
CAS: 114977-28-5
ATC: L01CD02
ĐG : Sanofi-Aventis Inc. , http://www.sanofi-aventis.com
CTHH: C43H53NO14
PTK: 807.8792
Docetaxel is a clinically well established anti-mitotic chemotherapy medication used mainly for the treatment of breast, ovarian, and non-small cell lung cancer. Docetaxel binds to microtubules reversibly with high affinity and has a maximum stoichiometry of one mole docetaxel per mole tubulin in microtubules.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C43H53NO14
Phân tử khối
807.8792
Monoisotopic mass
807.346605409
InChI
InChI=1S/C43H53NO14/c1-22-26(55-37(51)32(48)30(24-15-11-9-12-16-24)44-38(52)58-39(3,4)5)20-43(53)35(56-36(50)25-17-13-10-14-18-25)33-41(8,34(49)31(47)29(22)40(43,6)7)27(46)19-28-42(33,21-54-28)57-23(2)45/h9-18,26-28,30-33,35,46-48,53H,19-21H2,1-8H3,(H,44,52)/t26-,27-,28+,30-,31+,32+,33-,35-,41+,42-,43+/m0/s1
InChI Key
InChIKey=ZDZOTLJHXYCWBA-VCVYQWHSSA-N
IUPAC Name
(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetyloxy)-15-{[(2R,3S)-3-{[(tert-butoxy)carbonyl]amino}-2-hydroxy-3-phenylpropanoyl]oxy}-1,9,12-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0^{3,10}.0^{4,7}]heptadec-13-en-2-yl benzoate
Traditional IUPAC Name
(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetyloxy)-15-{[(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoyl]oxy}-1,9,12-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0^{3,10}.0^{4,7}]heptadec-13-en-2-yl benzoate
SMILES
[H][C@@]12C[C@H](O)[C@@]3(C)C(=O)[C@H](O)C4=C(C)[C@H](C[C@@](O)([C@@H](OC(=O)C5=CC=CC=C5)[C@]3([H])[C@@]1(CO2)OC(C)=O)C4(C)C)OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C1=CC=CC=C1
Độ tan chảy
232 °C
Độ hòa tan
Insoluble
logP
2.4
logS
-4.8
pKa (strongest acidic)
10.96
pKa (Strongest Basic)
-3
PSA
224.45 Å2
Refractivity
203.9 m3·mol-1
Polarizability
82.06 Å3
Rotatable Bond Count
13
H Bond Acceptor Count
10
H Bond Donor Count
5
Physiological Charge
0
Number of Rings
6
Bioavailability
0
MDDR-Like Rule
true
Dược Lực Học : Docetaxel is a taxoid antineoplastic agent. It promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, docetaxel induces abnormal arrays or "bundles" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.
Cơ Chế Tác Dụng : Docetaxel is a clinically well established anti-mitotic chemotherapy medication used mainly for the treatment of breast, ovarian, and non-small cell lung cancer. Docetaxel binds to microtubules reversibly with high affinity and has a maximum stoichiometry of one mole docetaxel per mole tubulin in microtubules. Docetaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, docetaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell's ability to use its cytoskeleton in a flexible manner. Specifically, docetaxel binds to the β-subunit of tubulin. Tubulin is the "building block" of mictotubules, and the binding of docetaxel locks these building blocks in place. The resulting microtubule/docetaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell. Chromosomes, for example, rely upon this property of microtubules during mitosis. Further research has indicated that docetaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl-2 (B-cell leukemia 2) and thus arresting its function.
Dược Động Học :
▧ Absorption :
The pharmacokinetic profile is consistent with a three-compartment model. The area under the curve (AUC) was dose proportional following doses of 70 mg/m2 to 115 mg/m2 with infusion times of 1 to 2 hours.
▧ Volume of Distribution :
The initial rapid decline represents distribution to the peripheral compartments and the late (terminal) phase is due, in part, to a relatively slow efflux of docetaxel from the peripheral compartment. * 113 L
▧ Protein binding :
In vitro studies show that 94% protein bound, mainly to a1-acid glycoprotein, albumin, and lipoproteins. When measured in cancer patients, docetaxel is 97% bound to plasma protein. Dexamethasone does not affect the protein binding of docetaxel.
▧ Metabolism :
Hepatic. In vitro drug interaction studies revealed that docetaxel is metabolized by the CYP3A4 isoenzyme (1 major, 3 minor metabolites).
▧ Route of Elimination :
Docetaxel was eliminated in both the urine and feces following oxidative metabolism of the tert-butyl ester group, but fecal excretion was the main elimination route. Within 7 days, urinary and fecal excretion accounted for approximately 6% and 75% of the administered radioactivity, respectively.
▧ Half Life :
Dose-dependent. Doses of 70 mg per square meter of body surface area (mg/m 2 ) or higher produce a triphasic elimination profile. With lower doses, assay limitations precluded detection of the terminal elimination phase. The half-life of the alpha, beta, and gamma phase are 4 minutes, 36 minutes, and 11.1 hours, respectively.
▧ Clearance :
* 21 L/h/m2 [Total body clearance, cancer patients after IV administration of 20–115 mg/m2]
Độc Tính : Oral LD50 in rat is >2000 mg/kg. Anticipated complications of overdosage include: bone marrow suppression, peripheral neurotoxicity, and mucositis. In two reports of overdose, one patient received 150 mg/m2 and the other received 200 mg/m2 as 1-hour infusions. Both patients experienced severe neutropenia, mild asthenia, cutaneous reactions, and mild paresthesia, and recovered without incident.
Chỉ Định : For the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy. Also used as a single agent in the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy. It is also used in combination with prednisone, in the treatment of patients with androgen independent (hormone refractory) metastatic prostate cancer. Furthermore, docetaxel has uses in the treatment of gastric adenocarinoma and head and neck cancer.
Tương Tác Thuốc :
  • Aprepitant Aprepitant may change levels of the chemotherapy agent, docetaxel.
  • Carboplatin Platinum derivatives such as carboplatin may enhance the myelosuppressive effect of taxane derivatives such as docetaxel. Administer taxane derivative before platinum derivative when given as sequential infusions to limit toxicity. Administering the taxane derivative before the platinum derivative seems prudent.
  • Cisplatin Platinum derivatives such as cisplatin may enhance the myelosuppressive effect of taxane derivatives such as docetaxel. Administer taxane derivative before platinum derivative when given as sequential infusions to limit toxicity. Administer paclitaxel before cisplatin, when given as sequential infusions, to limit toxicity. Problems associated with other taxane/platinum combinations are possible, although unsubstantiated. Administering the taxane derivative before the platinum derivative seems prudent.
  • Erythromycin Erythromycin may increase the serum levels and toxicity of docetaxel.
  • Josamycin Josamycin may increase the serum levels and toxicity of docetaxel.
  • Ketoconazole Ketoconazole may increase the serum levels and toxicity of docetaxel.
  • Midazolam Midazolam may increase the serum levels and toxicity of docetaxel.
  • Orphenadrine Orphenadrine may increase the serum levels and toxicity of docetaxel.
  • Quinupristin This combination presents an increased risk of toxicity.
  • Telithromycin Telithromycin may reduce clearance of Docetaxel. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Docetaxel if Telithromycin is initiated, discontinued or dose changed.
  • Testosterone Testosterone may increase the serum levels and toxicity of docetaxel.
  • Testosterone Propionate Testosterone propionate may increase the serum levels and toxicity of docetaxel.
  • Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
  • Valrubicin The taxane derivative, Docetaxel, may increase Valrubicin toxicity. Consider alternate therapy or monitor for toxic effects.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of docetaxel by decreasing its metabolism. Consider using a non-interacting antifungal or monitor for changes in the therapeutic and adverse effects of docetaxel if voriconazole is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng : Concentrate - Intravenous - 20 mg/mL; 80 mg/4 mL; 160 mg/8 mL; 20 mg/0.5 mL; 80 mg/2 mL
Solution - Intravenous - 20 mg/2 mL; 80 mg/8 mL; 160 mg/16 mL
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Docefrez
  • Công ty :
    Sản phẩm biệt dược : Taxotere
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01248
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=148124
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506766
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C11231
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D02165
ChemSpider
http://www.chemspider.com/Chemical-Structure.130581.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0075-8001-80
PharmGKB
http://www.pharmgkb.org/drug/PA449383
Wikipedia
http://en.wikipedia.org/wiki/Docetaxel
RxList
http://www.rxlist.com/cgi/generic3/docetaxel.htm
Drugs.com
http://www.drugs.com/cdi/docetaxel.html
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