You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameVinorelbine
Accession NumberDB00361  (APRD00101)
Typesmall molecule
Groupsapproved, investigational
Description

Vinorelbine (Navelbine®) is an anti-mitotic chemotherapy drug that is given as a treatment for some types of cancer, including breast cancer and non-small cell lung cancer. [Wikipedia]

Structure
Thumb
Synonyms
SynonymLanguageCode
5'-NoranhydrovinblastineNot AvailableIS
Nor-5'-anhydrovinblastineNot AvailableNot Available
VinorelbinGermanINN
VinorelbinaSpanishINN
VinorelbineNot AvailableDCF, BAN, USP 28,
VinorelbinumLatinINN
Salts
Name/CAS Structure Properties
Vinorelbine Ditartrate
Thumb Not applicable DBSALT001060
Vinorelbine Tartrate
Thumb
  • InChI Key: CILBMBUYJCWATM-KRQCOKQWSA-N
  • Monoisotopic Mass: 1078.427040572
  • Average Mass: 1079.1059
DBSALT000447
Brand names
NameCompany
BendarelbinBendalis
EberelbinEbewe
EunexonAC Farma
EurovinorelbinLapharm
FilcrinFilaxis
NavelbinPierre Fabre
NavelbinePierre Fabre
NavildezCryopharma
NavinCancernova
Navirelmedac
NeocitecSandoz
RenovelMustafa Nevzat
RiborelbinRibosepharm
VilneDosa
VinelbineGP-Pharm
VinorayneHospira
VinorelEriochem
VinorgenBago
VinotelFresenius
ZinavinNovamed
Brand mixturesNot Available
Categories
CAS number71486-22-1
WeightAverage: 778.9323
Monoisotopic: 778.394164724
Chemical FormulaC45H54N4O8
InChI KeyGBABOYUKABKIAF-GHYRFKGUSA-N
InChI
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
IUPAC Name
methyl (1R,9R,10R,11R,12R,19R)-11-(acetyloxy)-12-ethyl-4-[(12S,14R)-16-ethyl-12-(methoxycarbonyl)-1,10-diazatetracyclo[12.3.1.0^{3,11}.0^{4,9}]octadeca-3(11),4,6,8,15-pentaen-12-yl]-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.0^{1,9}.0^{2,7}.0^{16,19}]nonadeca-2,4,6,13-tetraene-10-carboxylate
SMILES
[H][C@@]12N(C)C3=CC(OC)=C(C=C3[C@@]11CCN3CC=C[C@@](CC)([C@@H](OC(C)=O)[C@@]2(O)C(=O)OC)[C@@]13[H])[C@]1(C[C@@]2([H])CN(CC(CC)=C2)CC2=C1NC1=CC=CC=C21)C(=O)OC
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassAlkaloids and Derivatives
ClassVinca Alkaloids
SubclassNot Available
Direct parentVinca Alkaloids
Alternative parentsRhazinilam Alkaloids; Plumeran-type Alkaloids; Ibogan-type Alkaloids; Carbazoles; Indoles; Anisoles; Tetrahydropyridines; Alkyl Aryl Ethers; Cyclohexanols; Dicarboxylic Acids and Derivatives; Tertiary Alcohols; Pyrrolidines; Pyrroles; Cyclic Alcohols and Derivatives; Carboxylic Acid Esters; Tertiary Amines; Enolates; Polyamines
Substituentsrhazinilam skeleton; plumeran skeleton; vindoline skeleton; catharanthine skeleton; carbazole; indole; indole or derivative; anisole; phenol ether; tetrahydropyridine; alkyl aryl ether; cyclohexanol; benzene; dicarboxylic acid derivative; pyrrole; pyrrolidine; tertiary alcohol; cyclic alcohol; tertiary amine; carboxylic acid ester; ether; enolate; polyamine; carboxylic acid derivative; alcohol; organonitrogen compound; amine
Classification descriptionThis compound belongs to the vinca alkaloids.
Pharmacology
IndicationFor the treatment of non-small-cell lung carcinoma.
PharmacodynamicsVinorelbine 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. Vinorelbine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death. Vinorelbine has some immunosuppressant effect. The vinca alkaloids are considered to be cell cycle phase-specific.
Mechanism of actionThe antitumor activity of vinorelbine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Vinorelbine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death. Like other vinca alkaloids, vinorelbine 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.
AbsorptionNot Available
Volume of distribution
  • 25.4 to 40.1 L/kg
Protein binding~27%
Metabolism
Route of eliminationVinorelbine undergoes substantial hepatic elimination in humans, with large amounts recovered in feces after intravenous administration to humans.
Half life27.7-43.6 hours
Clearance
  • 0.97 – 1.26 L/hr/kg
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Vinorelbine Action PathwayDrug actionSMP00439
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.974
Blood Brain Barrier - 0.8815
Caco-2 permeable + 0.5602
P-glycoprotein substrate Substrate 0.9283
P-glycoprotein inhibitor I Inhibitor 0.7488
P-glycoprotein inhibitor II Inhibitor 0.7388
Renal organic cation transporter Non-inhibitor 0.6979
CYP450 2C9 substrate Non-substrate 0.8513
CYP450 2D6 substrate Substrate 0.6471
CYP450 3A4 substrate Substrate 0.7247
CYP450 1A2 substrate Non-inhibitor 0.8415
CYP450 2C9 substrate Non-inhibitor 0.7863
CYP450 2D6 substrate Non-inhibitor 0.8369
CYP450 2C19 substrate Non-inhibitor 0.8381
CYP450 3A4 substrate Non-inhibitor 0.8095
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6672
Ames test Non AMES toxic 0.8064
Carcinogenicity Non-carcinogens 0.9299
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.8350 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9014
hERG inhibition (predictor II) Non-inhibitor 0.5171
Pharmacoeconomics
Manufacturers
  • Pierre fabre medicament
  • Actavis totowa llc
  • App pharmaceuticals llc
  • Baxter healthcare corp anesthesia and critical care
  • Bedford laboratories div ben venue laboratories inc
  • Ebewe pharma ges mbh nfg kg
  • Hospira inc
  • Teva parenteral medicines inc
Packagers
Dosage forms
FormRouteStrength
SolutionIntravenous
Prices
Unit descriptionCostUnit
Navelbine 50 mg/5 ml vial42.0USDml
Vinorelbine 50 mg/5 ml vial27.6USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP4Not Available
Predicted Properties
PropertyValueSource
water solubility1.22e-02 g/lALOGPS
logP4.39ALOGPS
logP4.65ChemAxon
logS-4.8ALOGPS
pKa (strongest acidic)10.87ChemAxon
pKa (strongest basic)8.72ChemAxon
physiological charge2ChemAxon
hydrogen acceptor count8ChemAxon
hydrogen donor count2ChemAxon
polar surface area133.87ChemAxon
rotatable bond count10ChemAxon
refractivity216.99ChemAxon
polarizability84.7ChemAxon
number of rings9ChemAxon
bioavailability1ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Marty M, Fumoleau P, Adenis A, Rousseau Y, Merrouche Y, Robinet G, Senac I, Puozzo C: Oral vinorelbine pharmacokinetics and absolute bioavailability study in patients with solid tumors. Ann Oncol. 2001 Nov;12(11):1643-9. Pubmed
External Links
ResourceLink
KEGG DrugD08680
ChEBI480999
ChEMBLCHEMBL607994
Therapeutic Targets DatabaseDAP000765
PharmGKBPA451881
Drug Product Database2257777
RxListhttp://www.rxlist.com/cgi/generic2/vinor.htm
Drugs.comhttp://www.drugs.com/cdi/vinorelbine.html
WikipediaVinorelbine
ATC CodesL01CA04
AHFS Codes
  • 10:00.00
PDB Entries
FDA labelshow(102 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AmprenavirAmprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Amprenavir is initiated, discontinued or dose changed.
AprepitantAprepitant may change levels of the chemotherapy agent, vinorelbine.
AtazanavirAtazanavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Atazanavir is initiated, discontinued or dose changed.
AtomoxetineThe CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
ClarithromycinClarithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vinorelbine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Clarithromycin is initiated, discontinued or dose changed.
ConivaptanConivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Conivaptan is initiated, discontinued or dose changed.
DarunavirDarunavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Darunavir is initiated, discontinued or dose changed.
DelavirdineDelavirdine, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Delavirdine is initiated, discontinued or dose changed.
DirithromycinDirithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vinorelbine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Dirithromycin is initiated, discontinued or dose changed.
ErythromycinErythromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vinorelbine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Erythromycin is initiated, discontinued or dose changed.
FosamprenavirFosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Fosamprenavir is initiated, discontinued or dose changed.
ImatinibImatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Imatinib is initiated, discontinued or dose changed.
IndinavirIndinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Indinavir is initiated, discontinued or dose changed.
IsoniazidIsoniazid, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Isoniazid is initiated, discontinued or dose changed.
ItraconazoleItraconazole, a strong CYP3A4 and p-glycoprotein inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism and/or increasing its efflux. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Itraconazole is initiated, discontinued or dose changed.
KetoconazoleKetoconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Ketoconazole is initiated, discontinued or dose changed.
LeflunomideVinorelbine 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 Vinorelbine, consider eliminating the loading dose of Leflunomide. Monitor for bone marrow suppression at least monthly during concomitant therapy.
LopinavirLopinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Lopinavir is initiated, discontinued or dose changed.
MiconazoleMiconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Miconazole is initiated, discontinued or dose changed.
NatalizumabConcomitant Vinorelbine and Natalizumab therapy may increase the risk of infection. Concurrent therapy should be avoided.
NefazodoneNafazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Nefazodone is initiated, discontinued or dose changed.
NelfinavirNelfinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Nelfinavir is initiated, discontinued or dose changed.
NicardipineNicardipine, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Nicardipine is initiated, discontinued or dose changed.
PosaconazolePosaconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Posaconazole is initiated, discontinued or dose changed.
QuinidineQuinidine, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Quinidine is initiated, discontinued or dose changed.
QuinupristinThis combination presents an increased risk of toxicity
RitonavirRitonavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Ritonavir is initiated, discontinued or dose changed.
SaquinavirSaquinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Saquinavir is initiated, discontinued or dose changed.
SpiramycinSpiramycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vinorelbine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Spiramycine is initiated, discontinued or dose changed.
TelithromycinTelithromycin, a CYP3A4 and p-glycoprotein inhibitor, may increase the Vinorelbine serum concentration and distribution in certain cells. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Telithromycin is initiated, discontinued or dose changed.
TrastuzumabTrastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Voriconazole is initiated, discontinued or dose changed.
Food InteractionsNot Available

Targets

1. Tubulin beta chain

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Tubulin beta chain P07437 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Kruczynski A, Barret JM, Etievant C, Colpaert F, Fahy J, Hill BT: Antimitotic and tubulin-interacting properties of vinflunine, a novel fluorinated Vinca alkaloid. Biochem Pharmacol. 1998 Mar 1;55(5):635-48. Pubmed
  4. Chang AY, Garrow GC: Pilot study of vinorelbine (Navelbine) and paclitaxel (Taxol) in patients with refractory breast cancer and lung cancer. Semin Oncol. 1995 Apr;22(2 Suppl 5):66-70; discussion 70-1. Pubmed
  5. Seve P, Dumontet C: [Class III beta tubulin expression in nonsmall cell lung cancer] Rev Mal Respir. 2010 Apr;27(4):383-6. Epub 2010 Mar 25. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. Pubmed

Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on March 17, 2014 16:12