| Revision as of 15:58, 10 January 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 456953721 of page Vinorelbine for the Chem/Drugbox validation project (updated: 'DrugBank', 'ChEMBL'). |
Latest revision as of 07:32, 30 November 2024 edit Whywhenwhohow (talk | contribs)Autopatrolled, Extended confirmed users, Pending changes reviewers49,136 edits EML |
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{{short description|Pharmaceutical drug}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
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{{cs1 config|name-list-style=vanc|display-authors=6}} |
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{{Drugbox |
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{{Drugbox |
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| Verifiedfields = changed |
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| Verifiedfields = changed |
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| Watchedfields = changed |
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| Watchedfields = changed |
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| verifiedrevid = 402875554 |
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| verifiedrevid = 470630496 |
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| IUPAC_name = 4-(acetyloxy)- 6,7-didehydro- 15-((2''R'',6''R'',8''S'')-4-ethyl- 1,3,6,7,8,9-hexahydro- 8-(methoxycarbonyl)- 2,6-methano- 2''H''-azecino(4,3-''b'')indol-8-yl)- 3-hydroxy- 16-methoxy- 1-methyl- methyl ester, |
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| IUPAC_name = Methyl (2β,3β,4β,5α,12β,19α)-4-acetoxy-15-octadeca-3(11),4,6,8,15-pentaen-12-yl]-3-hydroxy-16-methoxy-1-methyl-6,7-didehydroaspidospermidine-3-carboxylate |
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| image = Vinorelbine.svg |
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| image = Vinorelbine.svg |
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| image2 = Vinorelbine ball-and-stick.png |
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<!--Clinical data--> |
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<!--Clinical data--> |
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| tradename = Navelbine |
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| tradename = Navelbine |
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| Drugs.com = {{drugs.com|monograph|navelbine}} |
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| Drugs.com = {{drugs.com|monograph|vinorelbine-tartrate}} |
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| MedlinePlus = a695013 |
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| MedlinePlus = a695013 |
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| pregnancy_AU = D |
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| pregnancy_AU = D |
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| legal_UK = POM |
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| legal_UK = POM |
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| legal_US = Rx-only |
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| legal_US = Rx-only |
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| routes_of_administration = ], oral |
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| routes_of_administration = ], ]<ref name=BNF69/> |
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<!--Pharmacokinetic data--> |
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<!--Pharmacokinetic data--> |
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| bioavailability = 43 ± 14% (oral)<ref name = Marty>{{cite journal | author = Marty M, Fumoleau P, Adenis A, Rousseau Y, Merrouche Y, Robinet G, Senac I, Puozzo C | title = Oral vinorelbine pharmacokinetics and absolute bioavailability study in patients with solid tumors | journal = Ann Oncol | volume = 12 | issue = 11 | pages = 1643–9 | year = 2001 | pmid = 11822766 | doi = 10.1023/A:1013180903805}}</ref> |
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| bioavailability = 43 ± 14% (oral)<ref name = Marty>{{cite journal | vauthors = Marty M, Fumoleau P, Adenis A, Rousseau Y, Merrouche Y, Robinet G, Senac I, Puozzo C | title = Oral vinorelbine pharmacokinetics and absolute bioavailability study in patients with solid tumors | journal = Annals of Oncology | volume = 12 | issue = 11 | pages = 1643–1649 | date = November 2001 | pmid = 11822766 | doi = 10.1023/A:1013180903805 | doi-access = }}</ref> |
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| protein_bound = 79 to 91% |
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| protein_bound = 79 to 91% |
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| metabolism = ] (]-mediated) |
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| metabolism = ] (]-mediated) |
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| elimination_half-life = 27.7 to 43.6 hours |
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| elimination_half-life = 27.7 to 43.6 hours |
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| excretion = Fecal (46%) and ] (18%) |
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| excretion = Fecal (46%) and ] (18%) |
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<!--Identifiers--> |
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<!--Identifiers--> |
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| PubChem = 5311497 |
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| PubChem = 5311497 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = DB00361 |
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| DrugBank = DB00361 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 4470974 |
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| ChemSpiderID = 4470974 |
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| UNII_Ref = {{fdacite|changed|FDA}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = Q6C979R91Y |
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| UNII = Q6C979R91Y |
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| KEGG_Ref = {{keggcite|changed|kegg}} |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = D08680 |
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| KEGG = D08680 |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = <!-- blanked - oldvalue: 607994 --> |
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| ChEMBL = 607994 |
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<!--Chemical data--> |
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| C=45 | H=54 | N=4 | O=8 |
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| C=45 | H=54 | N=4 | O=8 |
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| smiles = 89C=C(CC)CN(Cc1c(c2ccccc12)(C(=O)OC)(c3cc4c(cc3OC)N(C)5()(O)(C(=O)OC)(OC(C)=O)7(CC)C=CCN6CC4567)C8)C9 |
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| molecular_weight = 778.932 g/mol |
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| smiles = O=C(OC)4(c2nc1ccccc1c2CN3CC(=C/(C3)C4)\CC)c5c(OC)cc6c(c5)89(N6C)(O)(C(=O)OC)(OC(=O)C)7(/C=C\CN(78)CC9)CC |
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| InChI = 1/C45H54N4O8/c1-8-27-19-28-22-44(40(51)55-6,36-30(25-48(23-27)24-28)29-13-10-11-14-33(29)46-36)32-20-31-34(21-35(32)54-5)47(4)38-43(31)16-18-49-17-12-15-42(9-2,37(43)49)39(57-26(3)50)45(38,53)41(52)56-7/h10-15,19-21,28,37-39,46,53H,8-9,16-18,22-25H2,1-7H3/t28-,37-,38+,39+,42+,43+,44-,45-/m0/s1 |
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| InChIKey = GBABOYUKABKIAF-IELIFDKJBG |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C45H54N4O8/c1-8-27-19-28-22-44(40(51)55-6,36-30(25-48(23-27)24-28)29-13-10-11-14-33(29)46-36)32-20-31-34(21-35(32)54-5)47(4)38-43(31)16-18-49-17-12-15-42(9-2,37(43)49)39(57-26(3)50)45(38,53)41(52)56-7/h10-15,19-21,28,37-39,46,53H,8-9,16-18,22-25H2,1-7H3/t28-,37-,38+,39+,42+,43+,44-,45-/m0/s1 |
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| StdInChI = 1S/C45H54N4O8/c1-8-27-19-28-22-44(40(51)55-6,36-30(25-48(23-27)24-28)29-13-10-11-14-33(29)46-36)32-20-31-34(21-35(32)54-5)47(4)38-43(31)16-18-49-17-12-15-42(9-2,37(43)49)39(57-26(3)50)45(38,53)41(52)56-7/h10-15,19-21,28,37-39,46,53H,8-9,16-18,22-25H2,1-7H3/t28-,37-,38+,39+,42+,43+,44-,45-/m0/s1 |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = GBABOYUKABKIAF-IELIFDKJSA-N |
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| StdInChIKey = GBABOYUKABKIAF-IELIFDKJSA-N |
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|drug_name=|alt=|caption=|type=|legal_status=|licence_EU=|pregnancy_category=|licence_US=|legal_CA=Rx-only|legal_AU=S4}} |
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}} |
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<!-- Definition and medical uses --> |
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'''Vinorelbine''' ('''NVB'''), sold under the brand name '''Navelbine''' among others, is a ] used to treat a number of types of cancer.<ref name=AHFS2016/> This includes ] and ].<ref name=AHFS2016/> It is given by ] or by mouth.<ref name=AHFS2016>{{cite web|title=Vinorelbine Tartrate|url=https://www.drugs.com/monograph/vinorelbine-tartrate.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161221162800/https://www.drugs.com/monograph/vinorelbine-tartrate.html|archive-date=21 December 2016}}</ref><ref name=BNF69/> |
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<!-- Side effects and mechanism --> |
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Common side effects include ], pain at the site of injection, vomiting, feeling tired, numbness, and diarrhea.<ref name=AHFS2016/> Other serious side effects include ].<ref name=AHFS2016/> Use during ] may harm the baby.<ref name=AHFS2016/> Vinorelbine is in the ] family of medications.<ref name=BNF69>{{cite book|title=British national formulary : BNF 69|date=2015|publisher=British Medical Association|isbn=9780857111562|page=594|edition=69}}</ref> It is believed to work by disrupting the normal function of ] and thereby stopping ].<ref name=AHFS2016/> |
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<!-- History society and culture --> |
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Vinorelbine was approved for medical use in the United States in 1994.<ref name=AHFS2016/> It is on the ].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref> |
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==Medical uses== |
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Vinorelbine is approved for the treatment of non-small-cell lung cancer.<ref name = MoleculesReview /><ref name = ClinMedInsight /> It is used off-label for other cancers such as ] and for ] (desmoid tumor).<ref>{{cite journal | vauthors = Saiyed MM, Ong PS, Chew L | title = Off-label drug use in oncology: a systematic review of literature | journal = Journal of Clinical Pharmacy and Therapeutics | volume = 42 | issue = 3 | pages = 251–258 | date = June 2017 | pmid = 28164359 | doi = 10.1111/jcpt.12507 | doi-access = free }}</ref><ref>{{cite journal | title = The management of desmoid tumours: A joint global consensus-based guideline approach for adult and paediatric patients | journal = European Journal of Cancer | volume = 127 | pages = 96–107 | date = March 2020 | pmid = 32004793 | doi = 10.1016/j.ejca.2019.11.013 | hdl = 2434/809127 | hdl-access = free | display-authors = 1 | vauthors = Alman B, Attia S, Baumgarten C, Benson C, Blay J, Bonvalot S, Breuing J, Cardona K, Casali PG, Van Coevorden F, Colombo C, Dei Tos AP, Dileo P, Ferrari A, Fiore M, Frezza AM, Garcia J, Gladdy R, Gounder M, Gronchi A, Haas R, Hackett S, Haller F, Hohenberger P, Husson O, Jones RL, Judson I, Kasper B, Kawai A, Kogosov V }}</ref> It is also active in ].<ref>{{cite journal | vauthors = Casanova M, Ferrari A, Spreafico F, Terenziani M, Massimino M, Luksch R, Cefalo G, Polastri D, Marcon I, Bellani FF | title = Vinorelbine in previously treated advanced childhood sarcomas: evidence of activity in rhabdomyosarcoma | journal = Cancer | volume = 94 | issue = 12 | pages = 3263–3268 | date = June 2002 | pmid = 12115359 | doi = 10.1002/cncr.10600 | s2cid = 21824468 | doi-access = free }}</ref> |
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==Side effects== |
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Vinorelbine has a number of side-effects that can limit its use: |
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] (a progressive, enduring and often irreversible tingling numbness, intense pain, and hypersensitivity to cold, beginning in the hands and feet and sometimes involving the arms and legs<ref name=NCI>{{cite journal | vauthors = del Pino BM | date = Feb 23, 2010 | journal = ] | volume = 7 | issue = 4 | page = 6 | title = Chemotherapy-induced Peripheral Neuropathy | url = http://www.cancer.gov/aboutnci/ncicancerbulletin/archive/2010/022310/page6 | archive-url = https://web.archive.org/web/20111211105234/http://www.cancer.gov/aboutnci/ncicancerbulletin/archive/2010/022310/page6 | url-status = dead | archive-date = 2011-12-11 }}</ref>), lowered resistance to infection, bruising or bleeding, ], ], vomitings, ], ], tiredness and a general feeling of weakness (]), inflammation of the vein into which it was injected (]). Seldom severe ] is seen. |
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Less common effects are hair loss and allergic reaction. |
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==Pharmacology== |
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The antitumor activity is due to inhibition of mitosis through interaction with tubulin.<ref>{{cite journal | vauthors = Jordan MA, Wilson L | title = Microtubules as a target for anticancer drugs | journal = Nature Reviews. Cancer | volume = 4 | issue = 4 | pages = 253–265 | date = April 2004 | pmid = 15057285 | doi = 10.1038/nrc1317 | s2cid = 10228718 }}</ref> |
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==History== |
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Vinorelbine was invented by the pharmacist ] and his team from the ] in ] in the 1980s and was licensed to the oncology department of the ]. The drug was approved in France in 1989 under the brand name Navelbine for the treatment of non-small cell ]. It gained approval to treat ] in 1991. Vinorelbine received approval by the ] ] (FDA) in December 1994 sponsored by Burroughs Wellcome Company. Pierre Fabre Group now markets Navelbine in the U.S., where the drug went generic in February 2003. |
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In most European countries, vinorelbine is approved to treat non-small cell lung cancer and breast cancer. In the United States it is approved only for non-small cell lung cancer. |
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===Sources=== |
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The Madagascan periwinkle '']'' L. is the source for a number of important natural products, including ] and ]<ref>{{cite book|chapter = ''Catharanthus roseus'' L. (Periwinkle): Production of Vindoline and Catharanthine in Multiple Shoot Cultures| vauthors = Hirata K, Miyamoto K, Miura Y |title = Biotechnology in Agriculture and Forestry 26|series = Medicinal and Aromatic Plants|volume = VI| veditors = Bajaj YP |publisher = ]|year = 1994|pages = |chapter-url = https://books.google.com/books?id=e64hCDBddowC&pg=PA47|isbn = 9783540563914|url = https://archive.org/details/medicinalaromati0006unse/page/46}}</ref> and the ]s it produces from them: ] and the ] agents ] and ], all of which can be obtained from the plant.<ref name=TopicsCurrentChem>{{cite book|title = Metal Catalyzed Reductive C—C Bond Formation: A Departure from Preformed Organometallic Reagents|volume = 279|series = Topics in Current Chemistry|pages = 25–52|year = 2007|chapter = Reductive C—C bond formation after epoxide opening via electron transfer | vauthors = Gansäuer A, Justicia J, Fan C, Worgull D, Piestert F |doi = 10.1007/128_2007_130|chapter-url = https://books.google.com/books?id=A5xcVmT9iIQC&pg=PA25| veditors = Krische MJ |editor-link1=Michael J. Krische |publisher = ]|isbn = 9783540728795|url-status = live|archive-url = https://web.archive.org/web/20170801195208/https://books.google.com.au/books?id=A5xcVmT9iIQC&pg=PA25|archive-date = 2017-08-01}}</ref><ref>{{cite book|chapter = Africa's gift to the world|pages = 46–51|chapter-url = https://books.google.com/books?id=aXGmCwAAQBAJ&pg=PA46|title = Botanical Miracles: Chemistry of Plants That Changed the World| vauthors = Cooper R, John J |publisher = ]|year = 2016|isbn = 9781498704304|url-status = live|archive-url = https://web.archive.org/web/20170801195333/https://books.google.com.au/books?id=aXGmCwAAQBAJ&pg=PA46|archive-date = 2017-08-01}}</ref><ref name=MoleculesReview>{{cite journal | vauthors = Keglevich P, Hazai L, Kalaus G, Szántay C | title = Modifications on the basic skeletons of vinblastine and vincristine | journal = Molecules | volume = 17 | issue = 5 | pages = 5893–5914 | date = May 2012 | pmid = 22609781 | pmc = 6268133 | doi = 10.3390/molecules17055893 | doi-access = free }}</ref><ref>{{cite book| vauthors = Raviña E |title = The evolution of drug discovery: From traditional medicines to modern drugs|year = 2011|publisher = ]|isbn = 9783527326693|pages = 157–159|chapter = Vinca alkaloids|chapter-url = https://books.google.com/books?id=iDNy0XxGqT8C&pg=PA157|url-status = live|archive-url = https://web.archive.org/web/20170801200844/https://books.google.ca/books?id=iDNy0XxGqT8C&pg=PA157|archive-date = 2017-08-01}}</ref> The newer ] chemotherapeutic agent vinorelbine, which is used in the treatment of ]<ref name = MoleculesReview /><ref name = ClinMedInsight>{{cite journal | vauthors = Faller BA, Pandit TN | title = Safety and efficacy of vinorelbine in the treatment of non-small cell lung cancer | journal = Clinical Medicine Insights: Oncology | volume = 5 | pages = 131–144 | year = 2011 | pmid = 21695100 | pmc = 3117629 | doi = 10.4137/CMO.S5074 }}</ref> and is not known to occur naturally. However, it can be prepared either from vindoline and catharanthine<ref name = MoleculesReview /><ref name = anhydro2vinorelbine>{{cite journal | vauthors = Ngo QA, Roussi F, Cormier A, Thoret S, Knossow M, Guénard D, Guéritte F | title = Synthesis and biological evaluation of vinca alkaloids and phomopsin hybrids | journal = Journal of Medicinal Chemistry | volume = 52 | issue = 1 | pages = 134–142 | date = January 2009 | pmid = 19072542 | doi = 10.1021/jm801064y }}</ref> or from leurosine,<ref name = Anhydro /> in both cases by synthesis of ]. The leurosine pathway uses the ] in a highly chemoselective de-oxygenation of leurosine.<ref>{{cite journal| vauthors = Morcillo SP, Miguel D, Campaña AG, de Cienfuegos LÁ, Justicia J, Cuerva JM |year = 2014|title = Recent applications of Cp<sub>2</sub>TiCl in natural product synthesis|journal = ]|volume = 1|issue = 1|pages = 15–33|doi = 10.1039/c3qo00024a|doi-access = free|hdl = 10481/47295|hdl-access = free}}</ref><ref name = Anhydro>{{cite journal | vauthors = Hardouin C, Doris E, Rousseau B, Mioskowski C | title = Concise synthesis of anhydrovinblastine from leurosine | journal = Organic Letters | volume = 4 | issue = 7 | pages = 1151–1153 | date = April 2002 | pmid = 11922805 | doi = 10.1021/ol025560c }}</ref> Anhydrovinblastine is then reacted sequentially with ] and ] followed by ] to yield vinorelbine.<ref name = anhydro2vinorelbine /> |
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==Oral formulation== |
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An oral formulation has been marketed and registered in most European countries. It has similar efficacy as the intravenous formulation, but it avoids venous toxicities of an infusion and is easier to take.{{medcn|date=May 2015}} The oral form is not approved in the United States, or Australia.{{medcn|date=May 2015}} |
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== References == |
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{{reflist}} |
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== External links == |
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* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/vinorelbine | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Vinorelbine }} |
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{{Chemotherapeutic agents}} |
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{{portal bar|Medicine}} |
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