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药品详细

Axitinib(阿西替尼)

化学结构式图
中文名
阿西替尼
英文名
Axitinib
分子式
Not Available
化学名
分子量
Not Available
CAS号
319460-85-0
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

Axitinib is an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3. Axitinib is marketed under the name Inlyta®, and if one previous systemic therapy for kidney cell cancer has failed, axitinib is indicated.

生产厂家
    封装厂家
    参考
    Synthesis Reference

    Hu-Lowe D, Hallin M, Feeley R, Zou H, Rewolinski D, Wickman G, Chen E, Kim Y, Riney S, Reed J, Heller D, Simmons B, Kania R, McTigue M, Niesman M, Gregory S, Shalinsky D, Bender S. Characterization of potency and activity of the VEGF/PDGF receptor tyrosine kinase inhibitor AG013736. Proc Am Assoc Cancer Res. 2002;43:A5357.
    General Reference
    1. Cohen EE, Rosen LS, Vokes EE, Kies MS, Forastiere AA, Worden FP, Kane MA, Sherman E, Kim S, Bycott P, Tortorici M, Shalinsky DR, Liau KF, Cohen RB: Axitinib Is an Active Treatment for All Histologic Subtypes of Advanced Thyroid Cancer: Results From a Phase II Study. J Clin Oncol. 2008 Jun 9. Pubmed
    2. Inai T, Mancuso M, Hashizume H, Baffert F, Haskell A, Baluk P, Hu-Lowe DD, Shalinsky DR, Thurston G, Yancopoulos GD, McDonald DM: Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. Am J Pathol. 2004 Jul;165(1):35-52. Pubmed
    3. Rugo HS, Herbst RS, Liu G, Park JW, Kies MS, Steinfeldt HM, Pithavala YK, Reich SD, Freddo JL, Wilding G: Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical results. J Clin Oncol. 2005 Aug 20;23(24):5474-83. Epub 2005 Jul 18. Pubmed
    4. Rini BI: SU11248 and AG013736: current data and future trials in renal cell carcinoma. Clin Genitourin Cancer. 2005 Dec;4(3):175-80. Pubmed
    5. Gilbert JA, Adhikari LJ, Lloyd RV, Halfdanarson TR, Muders MH, Ames MM: Molecular markers for novel therapeutic strategies in pancreatic endocrine tumors. Pancreas. 2013 Apr;42(3):411-21. doi: 10.1097/MPA.0b013e31826cb243. Pubmed
    6. FDA label.
    剂型
    规格
    化合物类型
    Type small molecule
    Classes Not Available
    Substructures Not Available
    适应症
    药理
    Indication Used in kidney cell cancer and investigated for use/treatment in pancreatic and thyroid cancer.
    Pharmacodynamics Axitinib prevents the progression of cancer by inhibiting angiogenesis and blocking tumor growth.
    Mechanism of action Axitinib selectively blocks the tyrosine kinase receptors VEGFR-1 (vascular endothelial growth factor receptor), VEGFR-2, and VEGFR-3.
    Absorption After one 5 mg dose of axitinib, it takes about 2.5 to 4.1 hours to reach maximum plasma concentration.
    Volume of distribution

    The volume of distribution is 160 L.
    Protein binding Plasma protein binding for axitinib is high at over 99% with most protein binding to albumin followed by α1-acid glycoprotein.
    Metabolism
    Axitinib undergoes mainly hepatic metabolism. CYP3A4 and CYP3A5 are the main hepatic enzymes while CYP1A2, CYP2C19, and UGT1A1 enzymes are secondary.
    Route of elimination Axitinib is mainly eliminated unchanged in the feces (41%) with 12% of the original dose as unchanged axitinib. There is also 23% eliminated in the urine, most of which are metabolites.
    Half life Axitinib has a half life of 2.5 to 6.1 hours.
    Clearance

    The average clearance of axitinib is 38 L/h.
    Toxicity Some of the more serious toxic effects seen in patients taking axitinib include, but are not limited to, hypertension, thrombotic events, hemorrhage, and GI perforation.
    Affected organisms
    • Humans and other mammals
    Pathways Not Available
    理化性质
    Properties
    State solid
    Experimental Properties
    Property Value Source
    water solubility In aqueous media with a pH between 1.1 to 7.8, axitinib has a solubility of over 0.2 μg/mL. From FDA label.
    pKa 4.8 From FDA label.
    Predicted Properties Not Available
    药物相互作用
    Drug Interaction
    Clobazam Clobazam decreases levels by affecting CYP3A4 metabolism. Consider alternate therapy.
    Etravirine Axitinib, when administered concomitantly with etravirine, may experience a decrease in serum concentrations. Recommended to avoid use of this combination.
    Paclitaxel Avoid combination due to potential for decrease in serum concentration of axitinib.
    Perampanel Avoid combination with axitinib or other major CYP3A4 drug susbtrates due to the potential decrease in the drug's concentration by perampanel induction of CYP3A4.
    Phenytoin Avoid combination with phenytoin and other strong, moderate, or weak CYP3A4 inducers due to the likely decreased levels of axitinib.
    St. John's Wort Avoid combination due to the likely decreased levels of axitinib.
    食物相互作用
    • Avoid combination with strong CYP3A4 inhibitors such as grapefruit juice due to the likely increased levels of axitinib. If the combination cannot be avoided, reduce axitinib dose by 50%.
    • Axitinib can be taken with or without food.

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