药品详细
Docetaxel (泰索帝 )
化学结构式图
中文名
泰索帝
英文名
Docetaxel
分子式
Not Available
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}-1,9,12-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
分子量
Average: 807.8792
Monoisotopic: 807.346605409
Monoisotopic: 807.346605409
CAS号
114977-28-5
ATC分类
L01C 植物碱和其他天然产物
药物类型
small molecule
阶段
商品名
Taxotere;
同义名
docetaxel;Docetaxel anhydrous;Docetaxel, Trihydrate;TXL;
基本介绍
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 1 mole docetaxel per mole tubulin in microtubules.
生产厂家
- Sanofi aventis us llc
封装厂家
参考
| Synthesis Reference | Not Available |
| General Reference | Not Available |
剂型
| Form | Route | Strength |
|---|---|---|
| Solution | Intravenous |
规格
| Unit description | Cost | Unit |
|---|---|---|
| Taxotere 20 mg/0.5 ml vial | 477.37 USD | vial |
化合物类型
| Type | small molecule |
| Classes |
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| Substructures |
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适应症
Cancer 癌症;
药理
| Indication | 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. Lastly, for use, in combination with prednisone, in the treatment of patients with androgen independent (hormone refractory) metastatic prostate cancer. | ||||||
| Pharmacodynamics | 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. | ||||||
| Mechanism of action | 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. | ||||||
| Absorption | Not Available | ||||||
| Volume of distribution |
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| Protein binding | About 94% protein bound, mainly to a1-acid glycoprotein, albumin, and lipoproteins. | ||||||
| Metabolism |
Hepatic. In vitro drug interaction studies revealed that docetaxel is metabolized by the CYP3A4 isoenzyme (1 major, 3 minor metabolites). |
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| 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. Alpha (distribution) 4 minutes. Beta 36 minutes. Gamma (terminal) 11.1 hours. | ||||||
| Clearance |
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| Toxicity | 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. | ||||||
| Affected organisms |
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| Pathways |
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理化性质
| Properties | |||||||||||||||||||||||||||||||||||||
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| State | solid | ||||||||||||||||||||||||||||||||||||
| Melting point | 232 oC | ||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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| Predicted Properties |
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药物相互作用
| Drug | Interaction |
|---|---|
| Aprepitant | Aprepitant may change levels of the chemotherapy agent, docetaxel. |
| 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. |
食物相互作用
Not Available
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