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药品详细

Cabazitaxel(卡巴他赛)

化学结构式图
中文名
卡巴他赛
英文名
Cabazitaxel
分子式
C45H57NO14
化学名
(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-hydroxy-9,12-dimethoxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0^{3,10}.0^{4,7}]heptadec-13-en-2-yl benzoate
分子量
Average: 835.9324
Monoisotopic: 835.377905537
CAS号
183133-96-2
ATC分类
L01C 植物碱和其他天然产物
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Cabazitaxel is an anti-neoplastic used with the steroid medicine prednisone. Cabazitaxel is used to treat people with prostate cancer that has progressed despite treatment with docetaxel. Cabazitaxel is prepared by semi-synthesis with a precursor extracted from yew needles (10-deacetylbaccatin III). It was approved by the U.S. Food and Drug Administration (FDA) on June 17, 2010.

生产厂家
    封装厂家
    参考
    Synthesis Reference Not Available
    General Reference
    1. Galsky MD, Dritselis A, Kirkpatrick P, Oh WK: Cabazitaxel. Nat Rev Drug Discov. 2010 Sep;9(9):677-8. Pubmed
    2. Kort A, Hillebrand MJ, Cirkel GA, Voest EE, Schinkel AH, Rosing H, Schellens JH, Beijnen JH: Quantification of cabazitaxel, its metabolite docetaxel and the determination of the demethylated metabolites RPR112698 and RPR123142 as docetaxel equivalents in human plasma by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Apr 15;925:117-23. doi: 10.1016/j.jchromb.2013.02.034. Epub 2013 Mar 5. Pubmed
    3. Nightingale G, Ryu J: Cabazitaxel (jevtana): a novel agent for metastatic castration-resistant prostate cancer. P T. 2012 Aug;37(8):440-8. Pubmed
    剂型
    规格
    化合物类型
    Type small molecule
    Classes Not Available
    Substructures
    • Taxanes
    适应症
    药理
    Indication For treatment of patients with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing treatment regimen.
    Pharmacodynamics Cabaitaxel has anti-tumour properties and is effective against docetaxel-sensitive and -insensitive tumours.
    Mechanism of action Cabazitaxel is a microtubule inhibitor. Cabazitaxel binds to tubulin and promotes its assembly into microtubules while simultaneously inhibiting disassembly. This leads to the stabilization of microtubules, which results in the interference of mitotic and interphase cellular functions. The cell is then unable to progress further into the cell cycle, being stalled at metaphase, thus triggering apoptosis of the cancer cell.
    Absorption After an intravenous dose of cabazitaxel 25 mg/m2 every three weeks to a population of 170 patients with solid tumors, the mean Cmax in patients with metastatic prostate cancer was 226 ng/mL (CV 107%) and was reached at the end of the one-hour infusion (Tmax). The mean AUC in patients with metastatic prostate cancer was 991 ng.h/mL (CV 34%). Administration with prednisone or prednisolone do not effect the pharmacokinetic profile of cabazitaxel.
    Volume of distribution

    The volume of distribution (Vss) was 4,864 L (2,643 L/m2 for a patient with a median BSA of 1.84 m2) at steady state. Compared to other taxanes, penetrates the CNS to a greater extent.
    Protein binding Cabazitaxel is mainly bound to human serum albumin (82%) and lipoproteins (88% for HDL, 70% for LDL, and 56% for VLDL).
    Metabolism
    Cabazitaxel is extensively metabolized in the liver (>95%), mainly by the CYP3A4/5 isoenzyme (80% to 90%), and to a lesser extent by CYP2C8 which results in 20 different metabolites. Two of these metabolites are active demethylated derivatives of cabaxitaxel and referred to as RPR112698 and RPR123142 respectively. Docetaxel is another metabolite of cabazitaxel. Cabazitaxel is the main circulating moiety in human plasma.

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

    Substrate Enzymes Product
    Cabazitaxel
      		Docetaxel Details
      Cabazitaxel
        		RPR112698 Details
        Cabazitaxel
          		RPR123142 Details
          Route of elimination After a one-hour intravenous infusion [14C]-cabazitaxel 25 mg/m2, approximately 80% of the administered dose was eliminated within 2 weeks. Cabazitaxel is mainly excreted in the feces as numerous metabolites (76% of the dose); while renal excretion of cabazitaxel and metabolites account for 3.7% of the dose (2.3% as unchanged drug in urine).
          Half life Following a one-hour intravenous infusion, plasma concentrations of cabazitaxel can be described by a three-compartment pharmacokinetic model with α-, β-, and γ- half-lives of 4 minutes, 2 hours, and 95 hours, respectively.
          Clearance

          Cabazitaxel has a plasma clearance of 48.5 L/h (CV 39%; 26.4 L/h/m2 for a patient with a median BSA of 1.84 m2) in patients with metastatic prostate cancer.
          Toxicity Cabazitaxel may cause serious side effects including neutropenia, hypersensitivity reactions, gastrointestinal symptoms, and renal failure. Anticipated complications of overdose include exacerbation of adverse reactions such as bone marrow suppression and gastrointestinal disorders. Cabazitaxel penetrates the blood-brain barrier. LD50, rat = 500 mg/kg
          Affected organisms
          • Humans and other mammals
          Pathways Not Available
          理化性质
          Properties
          State solid
          Experimental Properties Not Available
          Predicted Properties
          Property Value Source
          water solubility 4.13e-03 g/l ALOGPS
          logP 3.69 ALOGPS
          logP 4.2 ChemAxon
          logS -5.3 ALOGPS
          pKa (strongest acidic) 11.97 ChemAxon
          pKa (strongest basic) -3.6 ChemAxon
          physiological charge 0 ChemAxon
          hydrogen acceptor count 10 ChemAxon
          hydrogen donor count 3 ChemAxon
          polar surface area 202.45 ChemAxon
          rotatable bond count 15 ChemAxon
          refractivity 213.4 ChemAxon
          polarizability 86.39 ChemAxon
          药物相互作用
          Drug Interaction
          Atazanavir Concomitant therapy with a strong CYP3A4 inhibitor may increase concentrations of cabazitaxel. Avoid concomitant therapy.
          Carbamazepine Concomitant therapy with a strong CYP3A inducer may decrease concentrations of cabazitaxel. Avoid concomitant therapy.
          Cisplatin Platinum derivatives such as cisplatin may enhance the myelosuppressive effect of taxane derivatives such as cabazitaxel. 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.
          Clarithromycin Concomitant therapy with a strong CYP3A4 inhibitor may increase concentrations of cabazitaxel. Avoid concomitant therapy.
          Indinavir Concomitant therapy with a strong CYP3A4 inhibitor may increase concentrations of cabazitaxel. Avoid concomitant therapy.
          Itraconazole Concomitant therapy with a strong CYP3A4 inhibitor may increase concentrations of cabazitaxel. Avoid concomitant therapy.
          Ketoconazole Concomitant therapy with a strong CYP3A4 inhibitor may increase concentrations of cabazitaxel. Avoid concomitant therapy.
          Nefazodone Concomitant therapy with a strong CYP3A4 inhibitor may increase concentrations of cabazitaxel. Avoid concomitant therapy.
          Nelfinavir Concomitant therapy with a strong CYP3A4 inhibitor may increase concentrations of cabazitaxel. Avoid concomitant therapy.
          Phenobarbital Concomitant therapy with a strong CYP3A inducer may decrease concentrations of cabazitaxel. Avoid concomitant therapy.
          Phenytoin Concomitant therapy with a strong CYP3A inducer may decrease concentrations of cabazitaxel. Avoid concomitant therapy.
          Rifabutin Concomitant therapy with a strong CYP3A inducer may decrease concentrations of cabazitaxel. Avoid concomitant therapy.
          Rifampin Concomitant therapy with a strong CYP3A inducer may decrease concentrations of cabazitaxel. Avoid concomitant therapy.
          Rifapentine Concomitant therapy with a strong CYP3A inducer may decrease concentrations of cabazitaxel. Avoid concomitant therapy.
          Ritonavir Concomitant therapy with a strong CYP3A4 inhibitor may increase concentrations of cabazitaxel. Avoid concomitant therapy.
          Saquinavir Concomitant therapy with a strong CYP3A4 inhibitor may increase concentrations of cabazitaxel. Avoid concomitant therapy.
          St. John's Wort Concomitant therapy with a strong CYP3A inducer may decrease concentrations of cabazitaxel. Avoid concomitant therapy.
          Telithromycin Concomitant therapy with a strong CYP3A4 inhibitor may increase concentrations of cabazitaxel. Avoid concomitant therapy.
          Voriconazole Concomitant therapy with a strong CYP3A4 inhibitor may increase concentrations of cabazitaxel. Avoid concomitant therapy.
          食物相互作用
          Not Available

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