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药品详细

Sunitinib(舒尼替尼)

化学结构式图
中文名
舒尼替尼
英文名
Sunitinib
分子式
C22H27FN4O2
化学名
N-[2-(diethylamino)ethyl]-5-{[(3Z)-5-fluoro-2-oxo-2,3-dihydro-1H-indol-3-ylidene]methyl}-2,4-dimethyl-1H-pyrrole-3-carboxamide
分子量
Average: 398.4738
Monoisotopic: 398.211804333
CAS号
557795-19-4
ATC分类
L01X 其它抗肿瘤药
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Sunitinib is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) on January 26, 2006. Sunitinib inhibits cellular signaling by targeting multiple RTKs. These include all platelet-derived growth factor receptors (PDGF-R) and vascular endothelial growth factor receptors (VEGF-R). Sunitinib also inhibits KIT (CD117), the RTK that drives the majority of GISTs. In addition, sunitinib inhibits other RTKs including RET, CSF-1R, and flt3.

生产厂家
  • Cp pharmaceuticals international cv
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA: Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007 Jan 11;356(2):115-24. Pubmed
  2. Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG: Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006 Oct 14;368(9544):1329-38. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Statins
Substructures
  • Statins
  • Indoles and Indole Derivatives
  • Amino Ketones
  • Pyrroles
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Aliphatic and Aryl Amines
  • Halobenzenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Imines
  • Aryl Halides
适应症
药理
Indication For the treatment of advanced renal cell carcinoma as well as the treatment of gastrointestinal stromal tumor after disease progression on or intolerance to imatinib mesylate.
Pharmacodynamics Sunitinib is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA on January 26, 2006.
Mechanism of action Sunitinib is a small molecule that inhibits multiple RTKs, some of which are implicated in tumor growth, pathologic angiogenesis, and metastatic progression of cancer. Sunitinib was evaluated for its inhibitory activity against a variety of kinases (>80 kinases) and was identified as an inhibitor of platelet-derived growth factor receptors (PDGFRa and PDGFRb), vascular endothelial growth factor receptors (VEGFR1, VEGFR2 and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), colony stimulating factor receptor Type 1 (CSF-1R), and the glial cell-line derived neurotrophic factor receptor (RET). Sunitinib inhibition of the activity of these RTKs has been demonstrated in biochemical and cellular assays, and inhibition of function has been demonstrated in cell proliferation assays. The primary metabolite exhibits similar potency compared to sunitinib in biochemical and cellular assays.
Absorption Maximum plasma concentrations (Cmax) of sunitinib are generally observed between 6 and 12 hours (Tmax) following oral administration. Food has no effect on the bioavailability of sunitinib. Sunitinib may be taken with or without food.
Volume of distribution
  • 2230 L
Protein binding Binding of sunitinib and its primary metabolite to human plasma protein in vitro was 95% and 90%, respectively.
Metabolism
Sunitinib is metabolized primarily by the cytochrome P450 enzyme, CYP3A4, to produce its primary active metabolite, which is further metabolized by CYP3A4.
Route of elimination Sunitinib is metabolized primarily by the cytochrome P450 enzyme, CYP3A4, to produce its primary active metabolite, which is further metabolized by CYP3A4. Elimination is primarily via feces. In a human mass balance study of [14C]sunitinib, 61% of the dose was eliminated in feces, with renal elimination accounting for 16% of the administered dose.
Half life Following administration of a single oral dose in healthy volunteers, the terminal half-lives of sunitinib and its primary active metabolite are approximately 40 to 60 hours and 80 to 110 hours, respectively.
Clearance
  • Oral cl=34 – 62 L/h
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
logP 2.5 Not Available
Predicted Properties
Property Value Source
water solubility 3.08e-02 g/l ALOGPS
logP 3.24 ALOGPS
logP 2.93 ChemAxon
logS -4.1 ALOGPS
pKa (strongest acidic) 11.46 ChemAxon
pKa (strongest basic) 9.04 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 77.23 ChemAxon
rotatable bond count 7 ChemAxon
refractivity 116.27 ChemAxon
polarizability 44.32 ChemAxon
药物相互作用
Drug Interaction
Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Atazanavir Possible increase in sunitinib levels
Bevacizumab Sunitinib may enhance the adverse/toxic effect of bevacizumab. Specifically, the risk for a specific form of anemia, microangiopathic hemolytic anemia (MAHA), may be increased. Bevacizumab may enhance the hypertensive effect of sunitinib. This combination is contraindicated.
Carbamazepine Possible decrease in sunitinib levels
Clarithromycin Possible increase in sunitinib levels
Dexamethasone Possible decrease in sunitinib levels
Indinavir Possible increase in sunitinib levels
Itraconazole Possible increase in sunitinib levels
Ketoconazole Possible increase in sunitinib levels
Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Nefazodone Possible increase in sunitinib levels
Nelfinavir Possible increase in sunitinib levels
Phenobarbital Possible decrease in sunitinib levels
Phenytoin Possible decrease in sunitinib levels
Rifabutin Possible decrease in sunitinib levels
Rifampin Possible decrease in sunitinib levels
Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Telithromycin Telithromycin may reduce clearance of Sunitinib. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Sunitinib if Telithromycin is initiated, discontinued or dose changed.
Temsirolimus Co-administration of Temsirolimus and Sunitinib may result in serious adverse drug reactions.
Thiothixene May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Topotecan The p-glycoprotein inhibitor, Sunitinib, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
Toremifene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Trimipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of sunitinib by decreasing its metabolism. Additive QTc prolongation may also occur. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of sunitinib if voriconazole is initiated, discontinued or dose changed.
Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
食物相互作用
Not Available

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