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药品详细

Vinblastine(长春碱)

化学结构式图
中文名
长春碱
英文名
Vinblastine
分子式
C46H58N4O9
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]-10-hydroxy-5-methoxy-8-methyl-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: 810.9741
Monoisotopic: 810.420379474
CAS号
865-21-4
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
Nincaluicolflastine;Rozevin;Velban;Velbe;Vinblastin;Vinblastina [Dcit];Vinblastine Sulfate;Vinblastinum [INN-Latin];Vincaleucoblastin;Vincaleucoblastine;Vincaleukoblastine;Vincoblastine;
同义名
基本介绍

Antitumor alkaloid isolated from Vinca rosea. (Merck, 11th ed.)

生产厂家
  • Abraxis pharmaceutical products
  • App pharmaceuticals llc
  • Bedford laboratories div ben venue laboratories inc
  • Eli lilly and co
  • Hospira inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Starling D: Two ultrastructurally distinct tubulin paracrystals induced in sea-urchin eggs by vinblastine sulphate. J Cell Sci. 1976 Jan;20(1):79-89. 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
  • Aliphatic and Aryl Amines
  • Pyrroles
  • Phenylacetates
  • Short-chain Hydroxy Acids
  • Pyrrolidines
  • Ethers
  • Benzene and Derivatives
  • 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 breast cancer, testicular cancer, lymphomas, neuroblastoma, Hodgkin's and non-Hodgkin's lymphomas, mycosis fungoides, histiocytosis, and Kaposi's sarcoma.
Pharmacodynamics Vinblastine is a vinca alkaloid antineoplastic agent. 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. Vinblastine has some immunosuppressant effect. The vinca alkaloids are considered to be cell cycle phase-specific.
Mechanism of action The antitumor activity of vinblastine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Vinblastine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death.
Absorption Not Available
Volume of distribution Not Available
Protein binding 98-99%
Metabolism
Hepatic. Metabolism of vinblastine has been shown to be mediated by hepatic cytochrome P450 3A isoenzymes.

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

Substrate Enzymes Product
Vinblastine
Desacetylvinblastine Details
Route of elimination The major route of excretion may be through the biliary system.
Half life Triphasic: 35 min, 53 min, and 19 hours
Clearance Not Available
Toxicity Oral, mouse: LD50 = 423 mg/kg; Oral, rat: LD50 = 305 mg/kg.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00436 Vinblastine Pathway SMP00436
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 267 °C Not Available
water solubility Negligible Not Available
logP 3.70 SANGSTER (1994)
Predicted Properties
Property Value Source
water solubility 1.69e-02 g/l ALOGPS
logP 4.22 ALOGPS
logP 4.18 ChemAxon
logS -4.7 ALOGPS
pKa (strongest acidic) 10.87 ChemAxon
pKa (strongest basic) 8.86 ChemAxon
physiological charge 2 ChemAxon
hydrogen acceptor count 9 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 154.1 ChemAxon
rotatable bond count 10 ChemAxon
refractivity 222.42 ChemAxon
polarizability 87.3 ChemAxon
药物相互作用
Drug Interaction
Amprenavir Amprenavir, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Amprenavir is initiated, discontinued or dose changed.
Aprepitant Aprepitant may change levels of the chemotherapy agent, vinblastine.
Atazanavir Atazanavir, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Atazanavir is initiated, discontinued or dose changed.
Clarithromycin Clarithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vinblastine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Clarithromycin is initiated, discontinued or dose changed.
Conivaptan Conivaptan, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Conivaptan is initiated, discontinued or dose changed.
Dabigatran etexilate P-Glycoprotein inducers such as vinblastine may decrease the serum concentration of dabigatran etexilate. This combination should be avoided.
Darunavir Darunavir, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Darunavir is initiated, discontinued or dose changed.
Delavirdine Delavirdine, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Delavirdine is initiated, discontinued or dose changed.
Dirithromycin Dirithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vinblastine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Dirithromycin is initiated, discontinued or dose changed.
Erythromycin Erythromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the vinblastine serum concentration and distribution in certain cells. Consider alternate therapy to avoid vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of vinblastine if erythromycin is initiated, discontinued or dose changed.
Fluconazole Increases the effect and toxicity of anticancer agent
Fosamprenavir Fosamprenavir, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Fosamprenavir is initiated, discontinued or dose changed.
Fosphenytoin The antineoplasic agent decreases the effect of hydantoin
Imatinib Imatinib, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Imatinib is initiated, discontinued or dose changed.
Indinavir Indinavir, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Indinavir is initiated, discontinued or dose changed.
Isoniazid Isoniazid, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Isoniazid is initiated, discontinued or dose changed.
Itraconazole Itraconazole, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Itraconazole is initiated, discontinued or dose changed.
Ketoconazole Ketoconazole, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Ketoconazole is initiated, discontinued or dose changed.
Leflunomide Vinblastine 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 Vinblastine, consider eliminating the loading dose of Leflunomide. Monitor for bone marrow suppression at least monthly during concomitant therapy.
Lopinavir Lopinavir, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Lopinavir is initiated, discontinued or dose changed.
Miconazole Miconazole, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Miconazole is initiated, discontinued or dose changed.
Mitomycin Potentially severe lung toxicity
Natalizumab Concomitant Vinblastine and Natalizumab therapy may increase the risk of infection. Concurrent therapy should be avoided.
Nefazodone Nefazodone, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Nefazodone is initiated, discontinued or dose changed.
Nelfinavir Nelfinavir, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Nelfinavir is initiated, discontinued or dose changed.
Nicardipine Nicardipine, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Nicardipine is initiated, discontinued or dose changed.
Phenytoin The antineoplasic agent decreases the effect of hydantoin
Posaconazole Posaconazole, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Posaconazole is initiated, discontinued or dose changed.
Quinidine Quinidine, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Quinidine is initiated, discontinued or dose changed.
Quinupristin This combination presents an increased risk of toxicity
Ritonavir Ritonavir, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Ritonavir is initiated, discontinued or dose changed.
Saquinavir Saquinavir, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Saquinavir is initiated, discontinued or dose changed.
Spiramycin Spiramycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vinblastine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Spiramycin is initiated, discontinued or dose changed.
Telithromycin Telithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vinblastine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinblastine if Telithromycin is initiated, discontinued or dose changed.
Tolterodine Vinblastine, a CYP3A4 inhibitor, may increase the serum concentration of Tolterodine by decreasing its metabolism. Poor CYP2D6 metabolizers metabolize Tolterodine via CYP3A4. A dose adjustment of Tolterodine may be required. Monitor for changes in the therapeutic/adverse effects of Tolterodine if Vinblastine 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 decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Voriconazole is initiated, discontinued or dose changed.
食物相互作用
Not Available

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