Vincristine

Các tên gọi khác (6 ) :

22-Oxovincaleukoblastin
22-Oxovincaleukoblastine
Leurocristine
Vincristin
Vincristina
Vincristinum

Thuốc chống ung thư và tác động vào hệ thống miễn dịch

Thuốc Gốc

Small Molecule

CAS: 57-22-7

ATC: L01CA02

ĐG : APP Pharmaceuticals , http://www.apppharma.com

CTHH: C₄₆H₅₆N₄O₁₀

PTK: 824.9576

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 (liposomal injection) and Vincasar. Vincristine is indicated for the treatment of acute leukaemia, malignant lymphoma, Hodgkin's disease, acute erythraemia, and acute panmyelosis. vincristine sulfate is often chosen as part of polychemotherapy because of lack of significant bone–marrow suppression (at recommended doses) and of unique clinical toxicity (neuropathy).

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₄₆H₅₆N₄O₁₀

Phân tử khối

824.9576

Monoisotopic mass

824.399644032

InChI

InChI=1S/C46H56N4O10/c1-7-42(55)22-28-23-45(40(53)58-5,36-30(14-18-48(24-28)25-42)29-12-9-10-13-33(29)47-36)32-20-31-34(21-35(32)57-4)50(26-51)38-44(31)16-19-49-17-11-15-43(8-2,37(44)49)39(60-27(3)52)46(38,56)41(54)59-6/h9-13,15,20-21,26,28,37-39,47,55-56H,7-8,14,16-19,22-25H2,1-6H3/t28-,37+,38-,39-,42+,43-,44-,45+,46+/m1/s1

InChI Key

InChIKey=OGWKCGZFUXNPDA-XQKSVPLYSA-N

IUPAC Name

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

Traditional IUPAC Name

vincristine

SMILES

[H][C@@]12N3CC[C@@]11C4=CC(=C(OC)C=C4N(C=O)[C@@]1([H])[C@](O)([C@H](OC(C)=O)[C@]2(CC)C=CC3)C(=O)OC)[C@]1(C[C@]2([H])CN(C[C@](O)(CC)C2)CCC2=C1NC1=CC=CC=C21)C(=O)OC

Độ tan chảy

220 °C

Độ hòa tan

3.00e-02 g/l

logP

2.82

logS

-4.4

pKa (strongest acidic)

10.85

pKa (Strongest Basic)

8.66

PSA

171.17 Å²

Refractivity

221.48 m³·mol^-1

Polarizability

88.59 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

MDDR-Like Rule

true

pKa

Dược Lực Học : 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.

Cơ Chế Tác Dụng : 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 (liposomal injection) and Vincasar. Vincristine is indicated for the treatment of acute leukaemia, malignant lymphoma, Hodgkin's disease, acute erythraemia, and acute panmyelosis. vincristine sulfate is often chosen as part of polychemotherapy because of lack of significant bone–marrow suppression (at recommended doses) and of unique clinical toxicity (neuropathy). 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.

Dược Động Học :

▧ Volume of Distribution :
Within 15 to 30 minutes after injection, over 90% of the drug is distributed from the blood into tissue, where it remains tightly, but not irreversibly, bound.
▧ Protein binding :
~75%
▧ Metabolism :
Hepatic. Cytochrome P450 isoenzymes of the CYP3A subfamily facilitate the metabolism of vincristine.
▧ Route of Elimination :
The liver is the major excretory organ in humans and animals. 80% of an injected dose of vincristine sulfate is excreted via feces. 10 - 20% is excreted via urine.
▧ Half Life :
When intravenously injected into cancer patients, a triphasic serum decay patten was observed. The initial, middle, and terminal half-lives are 5 minutes, 2.3 hours, 85 hours respectively. The range of the terminal half-life is humans is 19 - 155 hours.

Độc Tính : 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. The most clinically significant adverse effect of vincristine is neurotoxicity.

Chỉ Định : Treatment of acute lymphocytic leukemia (ALL), Hodgkin lymphoma, non-Hodgkin lymphomas, Wilms' tumor, neuroblastoma, rhabdomyosarcoma. Liposomal vincristine is indicated for the treatment of relapsed Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL).

Tương Tác Thuốc :

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.

Liều Lượng & Cách Dùng : Injection, powder, lyophilized, for suspension - Intravenous - 5 mg/31 mL
Injection, solution - Intravenous - 1 mg/mL

Dữ Kiện Thương Mại

Giá thị trường

Biệt dược thương mại : Vincristine 2 mg/2 ml vial

Giá bán buôn : USD >18.06

Đơn vị tính : ml
Biệt dược thương mại : Oncovite tablet

Giá bán buôn : USD >0.19

Đơn vị tính : tablet

Nhà Sản Xuất

Công ty : Korea United Pharma

Sản phẩm biệt dược : Alcavixin
Công ty : Alkem

Sản phẩm biệt dược : Alcrist
Công ty : CSC

Sản phẩm biệt dược : Citomid
Công ty : Cipla

Sản phẩm biệt dược : Cytocristin
Công ty : TALON THERAP

Sản phẩm biệt dược : Marqibo
Công ty : Sun

Sản phẩm biệt dược : Oncocristin
Công ty : Lilly

Sản phẩm biệt dược : Oncovin
Công ty : Teva

Sản phẩm biệt dược : Oncrivin
Công ty : Actavis

Sản phẩm biệt dược : Sindovin
Công ty : Teva

Sản phẩm biệt dược : Tevacristin
Công ty : Ivax

Sản phẩm biệt dược : Vinces
Công ty : Teva

Sản phẩm biệt dược : Vincrisin
Công ty : Gedeon Richter

Sản phẩm biệt dược : Vincristin
Công ty : STADA

Sản phẩm biệt dược : Vincrisul
Công ty : Celon

Sản phẩm biệt dược : Vinlon
Công ty : Meizler

Sản phẩm biệt dược : Vinracine

Đóng gói

Công ty : APP Pharmaceuticals

Website : http://www.apppharma.com
Công ty : Hospira Inc.

Website : http://www.hospira.com
Công ty : Mission Pharmacal

Website : http://www.missionpharmacal.com
Công ty : Pharmacia Inc.

Website : http://www.pharmaciaupjohn.com
Công ty : Sicor Pharmaceuticals
Công ty : Teva Pharmaceutical Industries Ltd.

Website : http://www.tevapharm.com

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB00541

PubChem Compound

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5978

PubChem Substance

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46507033

KEGG Compound

http://www.genome.jp/dbget-bin/www_bget?cpd:C07204

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D08679

ChemSpider

http://www.chemspider.com/Chemical-Structure.5758.html

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/61703-309-06

PharmGKB

http://www.pharmgkb.org/drug/PA451879

Wikipedia

http://en.wikipedia.org/wiki/Vincristine

RxList

http://www.rxlist.com/cgi/generic3/vincristine.htm

Drugs.com

http://www.drugs.com/cdi/vincristine.html

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