Tìm theo
Paclitaxel
Các tên gọi khác (5 ) :
  • (2AR-(2aalpha,4beta,4abeta,6beta,9alpha(alpha r*,betas*),11alpha,12alpha,12balpha))-beta-(benzoylamino)-alpha-hydroxybenzenepropanoic acid 6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca(3,4)benz(1,2-b)oxet-9-yl ester
  • 5beta,20-Epoxy-1,2-alpha,4,7beta,10beta,13alpha-hexahydroxytax-11-en-9-one 4,10-diacetate 2-benzoate 13-ester with (2R,3S)-N-benzoyl-3-phenylisoserine
  • Paclitaxel
  • Taxol
  • Taxol A
Thuốc chống ung thư và tác động vào hệ thống miễn dịch
Thuốc Gốc
Small Molecule
CAS: 33069-62-4
ATC: L01CD01
ĐG : Abraxis BioScience Inc. , http://www.abraxisbio.com
CTHH: C47H51NO14
PTK: 853.9061
Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a US National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol. Later it was discovered that endophytic fungi in the bark synthesize paclitaxel. When it was developed commercially by Bristol-Myers Squibb (BMS), the generic name was changed to paclitaxel and the BMS compound is sold under the trademark Taxol. In this formulation, paclitaxel is dissolved in Kolliphor EL and ethanol, as a delivery agent. A newer formulation, in which paclitaxel is bound to albumin, is sold under the trademark Abraxane. [Wikipedia]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C47H51NO14
Phân tử khối
853.9061
Monoisotopic mass
853.330955345
InChI
InChI=1S/C47H51NO14/c1-25-31(60-43(56)36(52)35(28-16-10-7-11-17-28)48-41(54)29-18-12-8-13-19-29)23-47(57)40(61-42(55)30-20-14-9-15-21-30)38-45(6,32(51)22-33-46(38,24-58-33)62-27(3)50)39(53)37(59-26(2)49)34(25)44(47,4)5/h7-21,31-33,35-38,40,51-52,57H,22-24H2,1-6H3,(H,48,54)/t31-,32-,33+,35-,36+,37+,38-,40-,45+,46-,47+/m0/s1
InChI Key
InChIKey=RCINICONZNJXQF-MZXODVADSA-N
IUPAC Name
(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1,9-dihydroxy-15-{[(2R,3S)-2-hydroxy-3-phenyl-3-(phenylformamido)propanoyl]oxy}-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
paclitaxel
SMILES
[H][C@]12[C@H](OC(=O)C3=CC=CC=C3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)C4=CC=CC=C4)C4=CC=CC=C4)C(C)=C([C@@H](OC(C)=O)C(=O)[C@]1(C)[C@@H](O)C[C@H]1OC[C@@]21OC(C)=O)C3(C)C
Độ tan chảy
216-217 °C
Độ hòa tan
Insoluble
logP
3
logS
-5.2
pKa (strongest acidic)
10.36
pKa (Strongest Basic)
-1
PSA
221.29 Å2
Refractivity
218.29 m3·mol-1
Polarizability
87.17 Å3
Rotatable Bond Count
14
H Bond Acceptor Count
10
H Bond Donor Count
4
Physiological Charge
0
Number of Rings
7
Bioavailability
0
MDDR-Like Rule
true
Dược Lực Học : Paclitaxel is a taxoid antineoplastic agent indicated as first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary, and other various cancers including breast cancer. Paclitaxel is a novel antimicrotubule agent that 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, paclitaxel induces abnormal arrays or "bundles" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.
Cơ Chế Tác Dụng : Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a US National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol. Later it was discovered that endophytic fungi in the bark synthesize paclitaxel. When it was developed commercially by Bristol-Myers Squibb (BMS), the generic name was changed to paclitaxel and the BMS compound is sold under the trademark Taxol. In this formulation, paclitaxel is dissolved in Kolliphor EL and ethanol, as a delivery agent. A newer formulation, in which paclitaxel is bound to albumin, is sold under the trademark Abraxane. [Wikipedia] Paclitaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, paclitaxel 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, paclitaxel binds to the β subunit of tubulin. Tubulin is the "building block" of mictotubules, and the binding of paclitaxel locks these building blocks in place. The resulting microtubule/paclitaxel 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 paclitaxel 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 :
When a 24 hour infusion of 135 mg/m^2 is given to ovarian cancer patients, the maximum plasma concentration (Cmax) is 195 ng/mL, while the AUC is 6300 ng•h/mL.
▧ Volume of Distribution :
* 227 to 688 L/m^2 [apparent volume of distribution at steady-state, 24 hour infusion]
▧ Protein binding :
89%-98% bound to plasma protein. The presence of cimetidine, ranitidine, dexamethasone, or diphenhydramine did not affect protein binding of paclitaxel.
▧ Metabolism :
Hepatic. In vitro studies with human liver microsomes and tissue slices showed that paclitaxel was metabolized primarily to 6a-hydrox-ypaclitaxel by the cytochrome P450 isozyme CYP2C8; and to two minor metabolites, 3’-p-hydroxypaclitaxel and 6a, 3’-p-dihydroxypaclitaxel, by CYP3A4.
▧ Route of Elimination :
In 5 patients administered a 225 or 250 mg/m2 dose of radiolabeled paclitaxel as a 3-hour infusion, a mean of 71% of the radioactivity was excreted in the feces in 120 hours, and 14% was recovered in the urine.
▧ Half Life :
When a 24 hour infusion of 135 mg/m^2 is given to ovarian cancer patients, the elimination half=life is 52.7 hours.
▧ Clearance :
* 21.7 L/h/m2 [Dose 135 mg/m2, infusion duration 24 h] * 23.8 L/h/m2 [Dose 175 mg/m2, infusion duration 24 h] * 7 L/h/m2 [Dose 135 mg/m2, infusion duration 3 h] * 12.2 L/h/m2 [Dose 175 mg/m2, infusion duration 3 h]
Độc Tính : Rat (ipr) LD50=32530 µg/kg. Symptoms of overdose include bone marrow suppression, peripheral neurotoxicity, and mucositis. Overdoses in pediatric patients may be associated with acute ethanol toxicity.
Chỉ Định : Used in the treatment of Kaposi's sarcoma and cancer of the lung, ovarian, and breast. Abraxane® is specfically indicated for the treatment of metastatic breast cancer and locally advanced or metastatic non-small cell lung cancer.
Tương Tác Thuốc :
  • Aprepitant Aprepitant may change levels of the chemotherapy agent, paclitaxel.
  • Axitinib Avoid combination due to potential for decrease in serum concentration of axitinib.
  • Carboplatin Platinum derivatives such as carboplatin may enhance the myelosuppressive effect of taxane derivatives such as paclitaxel. 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 Cisplatin increases the effect and toxicity of paclitaxel
  • Clozapine Avoid combination due to the potential enhancement of agranulocytosis by clozapine.
  • Conivaptan Avoid combination because it will likely increase the serum concentration of CYP3A4 substrates.
  • Etravirine Paclitaxel, when used concomitantly with NNRTIs, may experience an increase in serum concentration. It is recommended to monitor for paclitaxel toxicity.
  • Gemcitabine Paclitaxel increases the effect/toxicity of gemcitabine
  • Natalizumab Avoid combination due to the increased risk of infection.
  • Pazopanib Pazopanib increases exposure of paclitaxel
  • Pimecrolimus Avoid combination due to the enhancement of adverse effects of immunosuppressants.
  • Quinupristin This combination presents an increased risk of toxicity
  • St. John's Wort Avoid combination due to potential decrease in serum concentration of paclitaxel.
  • Tacrolimus Avoid combination of topical tacrolimus due to the potential enhancement of adverse effects of immunosuppressants.
  • Telithromycin Telithromycin may reduce clearance of Paclitaxel. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Paclitaxel if Telithromycin is initiated, discontinued or dose changed.
  • Tolbutamide Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Paclitaxel. Consider alternate therapy or monitor for changes in Paclitaxel therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
  • Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Concomitant therapy may also increase Trastuzumab serum concentration and decrease Paclitaxel serum concentrations. Monitor closely for adverse events and therapeutic response.
  • Valrubicin The taxane derivative, Paclitaxel, may increase Valrubicin toxicity. Consider alternate therapy or monitor for toxic effects.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of paclitaxel by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of paclitaxel if voriconazole is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng : Concentrate - Intravenous - 100 mg/16.7 mL; 30 mg/5 mL; 150 mg/25 mL; 300 mg/50 mL
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Sản phẩm biệt dược : Abraxane
  • Công ty :
    Sản phẩm biệt dược : Onxol
  • Công ty :
    Sản phẩm biệt dược : Paxceed
  • Công ty :
    Sản phẩm biệt dược : Paxene
  • Công ty :
    Sản phẩm biệt dược : Taxol
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01229
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=36314
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506910
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07394
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00491
ChemSpider
http://www.chemspider.com/Chemical-Structure.33395.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0703-4764-01
PharmGKB
http://www.pharmgkb.org/drug/PA450761
Wikipedia
http://en.wikipedia.org/wiki/Paclitaxel
RxList
http://www.rxlist.com/cgi/generic/paclitaxel.htm
Drugs.com
http://www.drugs.com/cdi/paclitaxel.html
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