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Vinorelbine

January 29, 2023

Vinorelbine (NVB), sold under the brand name Navelbine among others, is a chemotherapy medication used to treat a number of types of cancer.[3] This includes breast cancer and non-small cell lung cancer.[3] It is given by injection into a vein or by mouth.[3][1]

Vinorelbine
Clinical data
Trade namesNavelbine
AHFS/Drugs.comMonograph
MedlinePlusa695013
Pregnancy
category
  • AU: D
Routes of
administration		intravenous, by mouth[1]
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability43 ± 14% (oral)[2]
Protein binding79 to 91%
Metabolismliver (CYP3A4-mediated)
Elimination half-life27.7 to 43.6 hours
ExcretionFecal (46%) and kidney (18%)
Identifiers
  • Methyl (2β,3β,4β,5α,12β,19α)-4-acetoxy-15-[(12S,14R)-16-ethyl-12-(methoxycarbonyl)-1,10-diazatetracyclo[12.3.1.03,11.04,9]octadeca-3(11),4,6,8,15-pentaen-12-yl]-3-hydroxy-16-methoxy-1-methyl-6,7-didehydroaspidospermidine-3-carboxylate
CAS Number
  • 71486-22-1 Y
PubChem CID
  • 5311497
DrugBank
  • DB00361 Y
ChemSpider
  • 4470974 Y
UNII
  • Q6C979R91Y
KEGG
  • D08680 Y
ChEMBL
  • ChEMBL607994 N
CompTox Dashboard (EPA)
  • DTXSID8040640
Chemical and physical data
FormulaC45H54N4O8
Molar mass778.947 g·mol−1
3D model (JSmol)
  • Interactive image
  • [H][C@]89C=C(CC)CN(Cc1c([nH]c2ccccc12)[C@@](C(=O)OC)(c3cc4c(cc3OC)N(C)[C@@]5([H])[C@@](O)(C(=O)OC)[C@H](OC(C)=O)[C@]7(CC)C=CCN6CC[C@]45[C@@]67[H])C8)C9
  • InChI=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 Y
  • Key:GBABOYUKABKIAF-IELIFDKJSA-N Y
 NY (what is this?)  (verify)

Common side effects include bone marrow suppression, pain at the site of injection, vomiting, feeling tired, numbness, and diarrhea.[3] Other serious side effects include shortness of breath.[3] Use during pregnancy may harm the baby.[3] Vinorelbine is in the vinca alkaloid family of medications.[1] It is believed to work by disrupting the normal function of microtubules and thereby stopping cell division.[3]

Vinorelbine was approved for medical use in the United States in 1994.[3] It is on the World Health Organization's List of Essential Medicines.[4][5]

Medical uses

Vinorelbine is approved for the treatment of non-small-cell lung cancer.[6][7] It is used off-label for other cancers such as metastatic breast cancer. It is also active in rhabdomyosarcoma.[8]

Side effects

Vinorelbine has a number of side-effects that can limit its use:

Chemotherapy-induced peripheral neuropathy (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[9]), lowered resistance to infection, bruising or bleeding, anaemia, constipation, vomitings, diarrhea, nausea, tiredness and a general feeling of weakness (asthenia), inflammation of the vein into which it was injected (phlebitis). Seldom severe hyponatremia is seen.

Less common effects are hair loss and allergic reaction.

Pharmacology

The antitumor activity is due to inhibition of mitosis through interaction with tubulin.[10]

History

Vinorelbine was invented by the pharmacist Pierre Potier and his team from the CNRS in France in the 1980s and was licensed to the oncology department of the Pierre Fabre Group. The drug was approved in France in 1989 under the brand name Navelbine for the treatment of non-small cell lung cancer. It gained approval to treat metastatic breast cancer in 1991. Vinorelbine received approval by the United States Food and Drug Administration (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.

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.

Sources

The Madagascan periwinkle Catharanthus roseus L. is the source for a number of important natural products, including catharanthine and vindoline[11] and the vinca alkaloids it produces from them: leurosine and the chemotherapy agents vinblastine and vincristine, all of which can be obtained from the plant.[12][13][6][14] The newer semi-synthetic chemotherapeutic agent vinorelbine, which is used in the treatment of non-small-cell lung cancer[6][7] and is not known to occur naturally. However, it can be prepared either from vindoline and catharanthine[6][15] or from leurosine,[16] in both cases by synthesis of anhydrovinblastine. The leurosine pathway uses the Nugent–RajanBabu reagent in a highly chemoselective de-oxygenation of leurosine.[17][16] Anhydrovinblastine is then reacted sequentially with N-bromosuccinimide and trifluoroacetic acid followed by silver tetrafluoroborate to yield vinorelbine.[15]

 

Oral formulation

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.[medical citation needed] The oral form is not approved in the United States, or Australia.[medical citation needed]

References

  1. ^ a b c British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 594. ISBN 9780857111562.
  2. ^ Marty M, Fumoleau P, Adenis A, Rousseau Y, Merrouche Y, Robinet G, Senac I, Puozzo C (2001). "Oral vinorelbine pharmacokinetics and absolute bioavailability study in patients with solid tumors". Ann Oncol. 12 (11): 1643–9. doi:10.1023/A:1013180903805. PMID 11822766.
  3. ^ a b c d e f g h "Vinorelbine Tartrate". The American Society of Health-System Pharmacists. from the original on 21 December 2016. Retrieved 8 December 2016.
  4. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  5. ^ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
  6. ^ a b c d Keglevich, Péter; Hazai, Laszlo; Kalaus, György; Szántay, Csaba (2012). "Modifications on the basic skeletons of vinblastine and vincristine". Molecules. 17 (5): 5893–5914. doi:10.3390/molecules17055893. PMC 6268133. PMID 22609781.
  7. ^ a b Faller, Bryan A.; Pandi, Trailokya N. (2011). "Safety and efficacy of vinorelbine in the treatment of non-small cell lung cancer". Clinical Medicine Insights: Oncology. 5: 131–144. doi:10.4137/CMO.S5074. PMC 3117629. PMID 21695100.
  8. ^ Casanova, Michela; Ferrari, Andrea; Spreafico, Filippo; Terenziani, Monica; Massimino, Maura; Luksch, Roberto; Cefalo, Graziella; Polastri, Daniela; Marcon, Ilaria; Bellani, Franca Fossati (2002). "Vinorelbine in previously treated advanced childhood sarcomas: Evidence of activity in rhabdomyosarcoma". Cancer. 94 (12): 3263–3268. doi:10.1002/cncr.10600. PMID 12115359. S2CID 21824468.
  9. ^ del Pino BM (Feb 23, 2010). . NCI Cancer Bulletin. 7 (4): 6. Archived from the original on 2011-12-11.
  10. ^ Jordan, M. A.; Wilson, L. (2004). "Microtubules as a target for anticancer drugs". Nature Reviews Cancer. 4 (4): 253–265. doi:10.1038/nrc1317. PMID 15057285. S2CID 10228718.
  11. ^ Hirata, K.; Miyamoto, K.; Miura, Y. (1994). "Catharanthus roseus L. (Periwinkle): Production of Vindoline and Catharanthine in Multiple Shoot Cultures". In Bajaj, Y. P. S. (ed.). Biotechnology in Agriculture and Forestry 26. Medicinal and Aromatic Plants. Vol. VI. Springer-Verlag. pp. 46–55. ISBN 9783540563914.
  12. ^ Gansäuer, Andreas; Justicia, José; Fan, Chun-An; Worgull, Dennis; Piestert, Frederik (2007). "Reductive C—C bond formation after epoxide opening via electron transfer". In Krische, Michael J. (ed.). Metal Catalyzed Reductive C—C Bond Formation: A Departure from Preformed Organometallic Reagents. Topics in Current Chemistry. Vol. 279. Springer Science & Business Media. pp. 25–52. doi:10.1007/128_2007_130. ISBN 9783540728795. from the original on 2017-08-01.
  13. ^ Cooper, Raymond; Deakin, Jeffrey John (2016). "Africa's gift to the world". Botanical Miracles: Chemistry of Plants That Changed the World. CRC Press. pp. 46–51. ISBN 9781498704304. from the original on 2017-08-01.
  14. ^ Raviña, Enrique (2011). "Vinca alkaloids". The evolution of drug discovery: From traditional medicines to modern drugs. John Wiley & Sons. pp. 157–159. ISBN 9783527326693. from the original on 2017-08-01.
  15. ^ a b Ngo, Quoc Anh; Roussi, Fanny; Cormier, Anthony; Thoret, Sylviane; Knossow, Marcel; Guénard, Daniel; Guéritte, Françoise (2009). "Synthesis and biological evaluation of Vinca alkaloids and phomopsin hybrids". Journal of Medicinal Chemistry. 52 (1): 134–142. doi:10.1021/jm801064y. PMID 19072542.
  16. ^ a b Hardouin, Christophe; Doris, Eric; Rousseau, Bernard; Mioskowski, Charles (2002). "Concise synthesis of anhydrovinblastine from leurosine". Organic Letters. 4 (7): 1151–1153. doi:10.1021/ol025560c. PMID 11922805.
  17. ^ Morcillo, Sara P.; Miguel, Delia; Campaña, Araceli G.; Cienfuegos, Luis Álvarez de; Justicia, José; Cuerva, Juan M. (2014). "Recent applications of Cp2TiCl in natural product synthesis". Organic Chemistry Frontiers. 1 (1): 15–33. doi:10.1039/c3qo00024a.

External links

  • "Vinorelbine". Drug Information Portal. U.S. National Library of Medicine.

January 29, 2023
vinorelbine, sold, under, brand, name, navelbine, among, others, chemotherapy, medication, used, treat, number, types, cancer, this, includes, breast, cancer, small, cell, lung, cancer, given, injection, into, vein, mouth, clinical, datatrade, namesnavelbineah. Vinorelbine NVB sold under the brand name Navelbine among others is a chemotherapy medication used to treat a number of types of cancer 3 This includes breast cancer and non small cell lung cancer 3 It is given by injection into a vein or by mouth 3 1 VinorelbineClinical dataTrade namesNavelbineAHFS Drugs comMonographMedlinePlusa695013PregnancycategoryAU DRoutes ofadministrationintravenous by mouth 1 ATC codeL01CA04 WHO Legal statusLegal statusAU S4 Prescription only CA only UK POM Prescription only US onlyPharmacokinetic dataBioavailability43 14 oral 2 Protein binding79 to 91 Metabolismliver CYP3A4 mediated Elimination half life27 7 to 43 6 hoursExcretionFecal 46 and kidney 18 IdentifiersIUPAC name Methyl 2b 3b 4b 5a 12b 19a 4 acetoxy 15 12S 14R 16 ethyl 12 methoxycarbonyl 1 10 diazatetracyclo 12 3 1 03 11 04 9 octadeca 3 11 4 6 8 15 pentaen 12 yl 3 hydroxy 16 methoxy 1 methyl 6 7 didehydroaspidospermidine 3 carboxylateCAS Number71486 22 1 YPubChem CID5311497DrugBankDB00361 YChemSpider4470974 YUNIIQ6C979R91YKEGGD08680 YChEMBLChEMBL607994 NCompTox Dashboard EPA DTXSID8040640Chemical and physical dataFormulaC 45H 54N 4O 8Molar mass778 947 g mol 13D model JSmol Interactive imageSMILES H C 89C C CC CN Cc1c nH c2ccccc12 C C O OC c3cc4c cc3OC N C C 5 H C O C O OC C H OC C O C 7 CC C CCN6CC C 45 C 67 H C8 C9InChI InChI 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 YKey GBABOYUKABKIAF IELIFDKJSA N Y N Y what is this verify Common side effects include bone marrow suppression pain at the site of injection vomiting feeling tired numbness and diarrhea 3 Other serious side effects include shortness of breath 3 Use during pregnancy may harm the baby 3 Vinorelbine is in the vinca alkaloid family of medications 1 It is believed to work by disrupting the normal function of microtubules and thereby stopping cell division 3 Vinorelbine was approved for medical use in the United States in 1994 3 It is on the World Health Organization s List of Essential Medicines 4 5 Contents 1 Medical uses 2 Side effects 3 Pharmacology 4 History 4 1 Sources 5 Oral formulation 6 References 7 External linksMedical uses EditVinorelbine is approved for the treatment of non small cell lung cancer 6 7 It is used off label for other cancers such as metastatic breast cancer It is also active in rhabdomyosarcoma 8 Side effects EditVinorelbine has a number of side effects that can limit its use Chemotherapy induced peripheral neuropathy 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 9 lowered resistance to infection bruising or bleeding anaemia constipation vomitings diarrhea nausea tiredness and a general feeling of weakness asthenia inflammation of the vein into which it was injected phlebitis Seldom severe hyponatremia is seen Less common effects are hair loss and allergic reaction Pharmacology EditThe antitumor activity is due to inhibition of mitosis through interaction with tubulin 10 History EditVinorelbine was invented by the pharmacist Pierre Potier and his team from the CNRS in France in the 1980s and was licensed to the oncology department of the Pierre Fabre Group The drug was approved in France in 1989 under the brand name Navelbine for the treatment of non small cell lung cancer It gained approval to treat metastatic breast cancer in 1991 Vinorelbine received approval by the United States Food and Drug Administration 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 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 Sources Edit The Madagascan periwinkle Catharanthus roseus L is the source for a number of important natural products including catharanthine and vindoline 11 and the vinca alkaloids it produces from them leurosine and the chemotherapy agents vinblastine and vincristine all of which can be obtained from the plant 12 13 6 14 The newer semi synthetic chemotherapeutic agent vinorelbine which is used in the treatment of non small cell lung cancer 6 7 and is not known to occur naturally However it can be prepared either from vindoline and catharanthine 6 15 or from leurosine 16 in both cases by synthesis of anhydrovinblastine The leurosine pathway uses the Nugent RajanBabu reagent in a highly chemoselective de oxygenation of leurosine 17 16 Anhydrovinblastine is then reacted sequentially with N bromosuccinimide and trifluoroacetic acid followed by silver tetrafluoroborate to yield vinorelbine 15 Oral formulation EditAn 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 medical citation needed The oral form is not approved in the United States or Australia medical citation needed References Edit a b c British national formulary BNF 69 69 ed British Medical Association 2015 p 594 ISBN 9780857111562 Marty M Fumoleau P Adenis A Rousseau Y Merrouche Y Robinet G Senac I Puozzo C 2001 Oral vinorelbine pharmacokinetics and absolute bioavailability study in patients with solid tumors Ann Oncol 12 11 1643 9 doi 10 1023 A 1013180903805 PMID 11822766 a b c d e f g h Vinorelbine Tartrate The American Society of Health System Pharmacists Archived from the original on 21 December 2016 Retrieved 8 December 2016 World Health Organization 2019 World Health Organization model list of essential medicines 21st list 2019 Geneva World Health Organization hdl 10665 325771 WHO MVP EMP IAU 2019 06 License CC BY NC SA 3 0 IGO World Health Organization 2021 World Health Organization model list of essential medicines 22nd list 2021 Geneva World Health Organization hdl 10665 345533 WHO MHP HPS EML 2021 02 a b c d Keglevich Peter Hazai Laszlo Kalaus Gyorgy Szantay Csaba 2012 Modifications on the basic skeletons of vinblastine and vincristine Molecules 17 5 5893 5914 doi 10 3390 molecules17055893 PMC 6268133 PMID 22609781 a b Faller Bryan A Pandi Trailokya N 2011 Safety and efficacy of vinorelbine in the treatment of non small cell lung cancer Clinical Medicine Insights Oncology 5 131 144 doi 10 4137 CMO S5074 PMC 3117629 PMID 21695100 Casanova Michela Ferrari Andrea Spreafico Filippo Terenziani Monica Massimino Maura Luksch Roberto Cefalo Graziella Polastri Daniela Marcon Ilaria Bellani Franca Fossati 2002 Vinorelbine in previously treated advanced childhood sarcomas Evidence of activity in rhabdomyosarcoma Cancer 94 12 3263 3268 doi 10 1002 cncr 10600 PMID 12115359 S2CID 21824468 del Pino BM Feb 23 2010 Chemotherapy induced Peripheral Neuropathy NCI Cancer Bulletin 7 4 6 Archived from the original on 2011 12 11 Jordan M A Wilson L 2004 Microtubules as a target for anticancer drugs Nature Reviews Cancer 4 4 253 265 doi 10 1038 nrc1317 PMID 15057285 S2CID 10228718 Hirata K Miyamoto K Miura Y 1994 Catharanthus roseus L Periwinkle Production of Vindoline and Catharanthine in Multiple Shoot Cultures In Bajaj Y P S ed Biotechnology in Agriculture and Forestry 26 Medicinal and Aromatic Plants Vol VI Springer Verlag pp 46 55 ISBN 9783540563914 Gansauer Andreas Justicia Jose Fan Chun An Worgull Dennis Piestert Frederik 2007 Reductive C C bond formation after epoxide opening via electron transfer In Krische Michael J ed Metal Catalyzed Reductive C C Bond Formation A Departure from Preformed Organometallic Reagents Topics in Current Chemistry Vol 279 Springer Science amp Business Media pp 25 52 doi 10 1007 128 2007 130 ISBN 9783540728795 Archived from the original on 2017 08 01 Cooper Raymond Deakin Jeffrey John 2016 Africa s gift to the world Botanical Miracles Chemistry of Plants That Changed the World CRC Press pp 46 51 ISBN 9781498704304 Archived from the original on 2017 08 01 Ravina Enrique 2011 Vinca alkaloids The evolution of drug discovery From traditional medicines to modern drugs John Wiley amp Sons pp 157 159 ISBN 9783527326693 Archived from the original on 2017 08 01 a b Ngo Quoc Anh Roussi Fanny Cormier Anthony Thoret Sylviane Knossow Marcel Guenard Daniel Gueritte Francoise 2009 Synthesis and biological evaluation of Vinca alkaloids and phomopsin hybrids Journal of Medicinal Chemistry 52 1 134 142 doi 10 1021 jm801064y PMID 19072542 a b Hardouin Christophe Doris Eric Rousseau Bernard Mioskowski Charles 2002 Concise synthesis of anhydrovinblastine from leurosine Organic Letters 4 7 1151 1153 doi 10 1021 ol025560c PMID 11922805 Morcillo Sara P Miguel Delia Campana Araceli G Cienfuegos Luis Alvarez de Justicia Jose Cuerva Juan M 2014 Recent applications of Cp2TiCl in natural product synthesis Organic Chemistry Frontiers 1 1 15 33 doi 10 1039 c3qo00024a External links Edit Vinorelbine Drug Information Portal U S National Library of Medicine Portal Medicine Retrieved from https en wikipedia org w index php title Vinorelbine amp oldid 1134779643, wikipedia, wiki, book, books, library,

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