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药品详细

Vincristine(长春新碱)

化学结构式图
中文名
长春新碱
英文名
Vincristine
分子式
C46H56N4O10
化学名
methyl (1R,9R,10S,11R,12R,19R)-11-(acetyloxy)-12-ethyl-4-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0^{4,12}.0^{5,10}]nonadeca-4(12),5,7,9-tetraen-13-yl]-8-formyl-10-hydroxy-5-methoxy-8,16-diazapentacyclo[10.6.1.0^{1,9}.0^{2,7}.0^{16,19}]nonadeca-2(7),3,5,13-tetraene-10-carboxylate
分子量
Average: 824.9576
Monoisotopic: 824.399644032
CAS号
57-22-7
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
Marqibo;Onco TCS;Oncovin;Vincasar;Vincasar PFS;Vincrex;Vincristine Sulfate PFS;Vinkristin;
同义名
22-Oxovincaleukoblastine;Indole alkaloid;LCR;Leurocristine;VCR;VIN;Vincristina [DCIT];vincristine;Vincristine Sulfate;Vincristinum [INN-Latin];Vincrstine;Vincrystine;Z-D-Val-Lys(Z)-OH;
基本介绍

Vincristine is an antitumor vinca alkaloid isolated from Vinca Rosea. It is marketed under several brand names, many of which have different formulations such as Marqibo and Vincasar. Vincristine is indicated for the treatment of acute leukaemia, malignant lymphoma, Hodgkin’s disease, acute erythraemia, and acute panmyelosis.

生产厂家
  • Abic ltd
  • Abraxis pharmaceutical products
  • App pharmaceuticals llc
  • Bristol myers squibb
  • Eli lilly and co
  • Hospira inc
  • Teva parenteral medicines inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Graf WD, Chance PF, Lensch MW, Eng LJ, Lipe HP, Bird TD: Severe vincristine neuropathy in Charcot-Marie-Tooth disease type 1A. Cancer. 1996 Apr 1;77(7):1356-62. Pubmed
  2. Qweider M, Gilsbach JM, Rohde V: Inadvertent intrathecal vincristine administration: a neurosurgical emergency. Case report. J Neurosurg Spine. 2007 Mar;6(3):280-3. Pubmed
  3. JOHNSON IS, ARMSTRONG JG, GORMAN M, BURNETT JP Jr: THE VINCA ALKALOIDS: A NEW CLASS OF ONCOLYTIC AGENTS. Cancer Res. 1963 Sep;23:1390-427. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Tryptamines and Derivatives
Substructures
  • Carbonyl Compounds
  • Carboxylic Acids and Derivatives
  • Glycerol and Derivatives
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Acetates
  • Indoles and Indole Derivatives
  • Phenols and Derivatives
  • Pyrroles
  • Phenylacetates
  • Short-chain Hydroxy Acids
  • Pyrrolidines
  • Ethers
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Alcohols and Polyols
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Phenylpropylamines
  • Tryptamines and Derivatives
  • Imines
  • Phenyl Esters
  • Anilines
  • Amphetamines
  • Piperidines
  • Pyrrolines
适应症
Cancer 癌症;
药理
Indication For treatment of acute leukaemia, malignant lymphoma, Hodgkin's disease, acute erythraemia, acute panmyelosis.
Pharmacodynamics Vincristine is a vinca alkaloid antineoplastic agent used as a treatment for various cancers including breast cancer, Hodgkin's disease, Kaposi's sarcoma, and testicular cancer. The vinca alkaloids are structurally similar compounds comprised of 2 multiringed units, vindoline and catharanthine. The vinca alkaloids have become clinically useful since the discovery of their antitumour properties in 1959. Initially, extracts of the periwinkle plant (Catharanthus roseus) were investigated because of putative hypoglycemic properties, but were noted to cause marrow suppression in rats and antileukemic effects in vitro. Vincristine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death. Vincristine has some immunosuppressant effect. The vinca alkaloids are considered to be cell cycle phase-specific.
Mechanism of action The antitumor activity of Vincristine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Like other vinca alkaloids, Vincristine may also interfere with: 1) amino acid, cyclic AMP, and glutathione metabolism, 2) calmodulin-dependent Ca2+-transport ATPase activity, 3) cellular respiration, and 4) nucleic acid and lipid biosynthesis.
Absorption Not Available
Volume of distribution Not Available
Protein binding ~75%
Metabolism
Hepatic
Route of elimination Not Available
Half life 19-155 hours
Clearance Not Available
Toxicity IVN-RAT LD50 1300 mg/kg; IPR-MUS LD50 5.2 mg/kg. Marqibo® must only be administered IV because it is fatal if administered by other routes. Marqibo® also has different dosing than vincristine sulphate injection, so attention is needed to prevent overdoses.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00437 Vincristine Pathway SMP00437
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 220 °C PhysProp
logP 2.82 HANSCH,C ET AL. (1995)
pKa 5 MERCK INDEX (1996)
Predicted Properties
Property Value Source
water solubility 3.00e-02 g/l ALOGPS
logP 3.36 ALOGPS
logP 3.13 ChemAxon
logS -4.4 ALOGPS
pKa (strongest acidic) 10.85 ChemAxon
pKa (strongest basic) 8.66 ChemAxon
physiological charge 2 ChemAxon
hydrogen acceptor count 9 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 171.17 ChemAxon
rotatable bond count 10 ChemAxon
refractivity 221.48 ChemAxon
polarizability 88.59 ChemAxon
药物相互作用
Drug Interaction
Amprenavir Amprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Amprenavir is initiated, discontinued or dose changed.
Aprepitant Aprepitant may change levels of the chemotherapy agent, vincristine.
Atazanavir Atazanavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Atazanavir is initiated, discontinued or dose changed.
Clarithromycin Clarithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vincristine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Clarithromycin is initiated, discontinued or dose changed.
Conivaptan Conivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Conivaptan is initiated, discontinued or dose changed.
Darunavir Darunavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Darunavir is initiated, discontinued or dose changed.
Delavirdine Delavirdine, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Delavirdine is initiated, discontinued or dose changed.
Digoxin The antineoplasic agent decreases the effect of digoxin
Dirithromycin Dirithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vincristine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Dirithromycin is initiated, discontinued or dose changed.
Erythromycin Erythromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vincristine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Erythromycin is initiated, discontinued or dose changed.
Etravirine Vincristine, when used concomitantly with etravirine, may experience a decrease in serum concentration. It is recommended to avoid concurrent therapy.
Fluconazole Increases the effect and toxicity of anticancer agent
Fosamprenavir Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Fosamprenavir is initiated, discontinued or dose changed.
Imatinib Imatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Imatinib is initiated, discontinued or dose changed.
Indinavir Indinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Indinavir is initiated, discontinued or dose changed.
Isoniazid Isoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Isoniazid is initiated, discontinued or dose changed.
Itraconazole Itraconazole, a strong CYP3A4 and p-glycoprotein inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism and/or increasing efflux. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Itraconazole is initiated, discontinued or dose changed.
Ketoconazole Ketoconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Ketoconazole is initiated, discontinued or dose changed.
Leflunomide Vincristine may increase the adverse/toxic effects of Leflunomide. This may increase the risk of hematologic toxicities such as pancytopenia, agranulocytosis and thrombocytopenia. In patients receiving Vincristine, consider eliminating the loading dose of Leflunomide. Monitor for bone marrow suppression at least monthly during concomitant therapy.
Lopinavir Lopinavir, a strong CYP3A4 and p-glycoprotein inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism and/or increasing its efflux. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Lopinavir is initiated, discontinued or dose changed.
Miconazole Miconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Miconazole is initiated, discontinued or dose changed.
Mitomycin Potentially severe lung toxicity
Natalizumab Concomitant Vincristine and Natalizumab therapy may increase the risk of infection. Concurrent therapy should be avoided.
Nefazodone Nefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Nefazodone is initiated, discontinued or dose changed.
Nelfinavir Nelfinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Nelfinavir is initiated, discontinued or dose changed.
Nicardipine Nicardipine, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Nicardipine is initiated, discontinued or dose changed.
Posaconazole Posaconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Posaconazole is initiated, discontinued or dose changed.
Quinidine Quinidine, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Quinidine is initiated, discontinued or dose changed.
Quinupristin This combination presents an increased risk of toxicity
Ritonavir Ritonavir, a strong CYP3A4 and p-glycoprotein inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism and/or increasing efflux. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Ritonavir is initiated, discontinued or dose changed.
Saquinavir Saquinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Saquinavir is initiated, discontinued or dose changed.
Spiramycin Spiramycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vincristine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Spiramycin is initiated, discontinued or dose changed.
Telithromycin Telithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vincristine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Telithromycin is initiated, discontinued or dose changed.
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Voriconazole is initiated, discontinued or dose changed.
食物相互作用
Not Available

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