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Identification
Name Vancomycin
Accession Number DB00512 (APRD01287, EXPT03217)
Type small molecule
Groups approved
Description

Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Vancomycin HCL
Salts Not Available
Brand names
Name Company
Vancocin
Vancocin HCL
Vancoled
Vancor
Brand mixtures Not Available
Categories
  • Anti-Bacterial Agents
  • Glycopeptide antibacterials
CAS number 1404-90-6
Weight Average: 1449.254
Monoisotopic: 1447.430199787
Chemical Formula C66H75Cl2N9O24
InChI Key InChIKey=MYPYJXKWCTUITO-LYRMYLQWSA-N
InChI
InChI=1S/C66H75Cl2N9O24/c1-23(2)12-34(71-5)58(88)76-49-51(83)26-7-10-38(32(67)14-26)97-40-16-28-17-41(55(40)101-65-56(54(86)53(85)42(22-78)99-65)100-44-21-66(4,70)57(87)24(3)96-44)98-39-11-8-27(15-33(39)68)52(84)50-63(93)75-48(64(94)95)31-18-29(79)19-37(81)45(31)30-13-25(6-9-36(30)80)46(60(90)77-50)74-61(91)47(28)73-59(89)35(20-43(69)82)72-62(49)92/h6-11,13-19,23-24,34-35,42,44,46-54,56-57,65,71,78-81,83-87H,12,20-22,70H2,1-5H3,(H2,69,82)(H,72,92)(H,73,89)(H,74,91)(H,75,93)(H,76,88)(H,77,90)(H,94,95)/t24-,34+,35-,42+,44-,46+,47+,48-,49+,50-,51+,52+,53+,54-,56+,57+,65-,66-/m0/s1
Plain Text
IUPAC Name
(1S,2R,18R,19R,22S,25R,28R,40S)-48-{[(2S,3R,4S,5S,6R)-3-{[(2S,4S,5S,6S)-4-amino-5-hydroxy-4,6-dimethyloxan-2-yl]oxy}-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-22-(carbamoylmethyl)-5,47-dichloro-2,18,32,35,37-pentahydroxy-19-[(2R)-4-methyl-2-(methylamino)pentanamido]-20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentaazaoctacyclo[26.14.2.2^{3,6}.2^{14,17}.1^{8,12}.1^{29,33}.0^{10,25}.0^{34,39}]pentaconta-3,5,8,10,12(48),14,16,29(45),30,32,34,36,38,46,49-pentadecaene-40-carboxylic acid
SMILES
CN[C@H](CC(C)C)C(=O)N[C@@H]1[C@H](O)C2=CC=C(OC3=C(O[C@@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@H]4O[C@H]4C[C@](C)(N)[C@H](O)[C@H](C)O4)C4=CC(=C3)[C@@H](NC(=O)[C@H](CC(N)=O)NC1=O)C(=O)N[C@@H]1C3=CC(=C(O)C=C3)C3=C(O)C=C(O)C=C3[C@H](NC(=O)[C@@H](NC1=O)[C@H](O)C1=CC(Cl)=C(O4)C=C1)C(O)=O)C(Cl)=C2
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Carbohydrates
  • Biphenyl and Derivatives
  • Polypeptides
  • Lactams
  • Catecholamines and Derivatives
Substructures
  • Glycerol and Derivatives
  • Hydroxy Compounds
  • Phenols and Derivatives
  • Pyrans
  • Benzyl Alcohols and Derivatives
  • Acetates
  • Acetals and Derivatives
  • Aliphatic and Aryl Amines
  • Amino Ketones
  • Carbohydrates
  • Carboxylic Acids and Derivatives
  • Phenylpropenes
  • Phenylacetates
  • Ethers
  • Benzene and Derivatives
  • Biphenyl and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Carbamates and Derivatives
  • Alcohols and Polyols
  • Amino Alcohols
  • Catechols
  • Phenethylamines
  • Polypeptides
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Carboxamides and Derivatives
  • Phenylpropylamines
  • Amino Acids
  • Lactams
  • Phenyl Esters
  • Amphetamines
  • Resorcinols
  • Catecholamines and Derivatives
Pharmacology
Indication For the treatment of serious or severe infections caused by susceptible strains of methicillin-resistant (beta-lactam-resistant) staphylococci.
Pharmacodynamics Vancomycin is a branched tricyclic glycosylated nonribosomal peptide produced by the fermentation of the Actinobacteria species Amycolatopsis orientalis (formerly Nocardia orientalis). It is often reserved as the "drug of last resort", used only after treatment with other antibiotics had failed. Vancomycin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections: Listeria monocytogenes, Streptococcus pyogenes, Streptococcus pneumoniae (including penicillin-resistant strains), Streptococcus agalactiae, Actinomyces species, and Lactobacillus species. The combination of vancomycin and an aminoglycoside acts synergistically in vitro against many strains of Staphylococcus aureus, Streptococcus bovis, enterococci, and the viridans group streptococci.
Mechanism of action The bactericidal action of vancomycin results primarily from inhibition of cell-wall biosynthesis. Specifically, vancomycin prevents incorporation of N-acetylmuramic acid (NAM)- and N-acetylglucosamine (NAG)-peptide subunits from being incorporated into the peptidoglycan matrix; which forms the major structural component of Gram-positive cell walls. The large hydrophilic molecule is able to form hydrogen bond interactions with the terminal D-alanyl-D-alanine moieties of the NAM/NAG-peptides. Normally this is a five-point interaction. This binding of vancomycin to the D-Ala-D-Ala prevents the incorporation of the NAM/NAG-peptide subunits into the peptidoglycan matrix. In addition, vancomycin alters bacterial-cell-membrane permeability and RNA synthesis. There is no cross-resistance between vancomycin and other antibiotics. Vancomycin is not active in vitro against gram-negative bacilli, mycobacteria, or fungi.
Absorption Poorly absorbed from gastrointestinal tract, however systemic absorption (up to 60%) may occur following intraperitoneal administration.
Volume of distribution Not Available
Protein binding Approximately 55% serum protein bound.
Metabolism Not Available
Route of elimination In the first 24 hours, about 75% of an administered dose of vancomycin is excreted in urine by glomerular filtration.
Half life Half-life in normal renal patients is approximately 6 hours (range 4 to 11 hours). In anephric patients, the average half-life of elimination is 7.5 days.
Clearance
  • 0.06 L/kg/h
Toxicity The oral LD50 in mice is 5000 mg/kg. The median lethal intravenous dose is 319 mg/kg in rats and 400 mg/kg in mice.
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Viropharma inc
  • Lederle parenterals inc
  • Baxter healthcare corp
  • Baxter healthcare corp anesthesia and critical care
  • Akorn strides llc
  • App pharmaceuticals llc
  • Bioniche pharma usa llc
  • Hospira inc
  • Sandoz inc
  • Pharmacia and upjohn co
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Capsule Oral
Powder, for solution Intravenous
Prices
Unit description Cost Unit
Vancocin HCl 20 250 mg capsule Box 1019.87 USD box
Vancomycin hcl powder 85.68 USD g
Pms-Vancomycin 1 g/vial 61.98 USD vial
Vancocin hcl 250 mg pulvule 40.97 USD each
Pms-Vancomycin 500 mg/vial 32.62 USD vial
Vancocin HCl 125 mg capsule 27.66 USD capsule
Vancocin hcl 125 mg pulvule 22.22 USD each
Vancomycin 1 gm vial 7.0 USD vial
Vancomycin hcl 750 mg vial 5.72 USD vial
Vancomycin 500 mg vial 3.74 USD vial
Vancomycin-ns 1.5 g/150 ml 0.24 USD ml
Vancomycin-ns 1.25 g/150 ml 0.21 USD ml
Vancomycin hcl 1 g/200 ml bag 0.17 USD ml
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Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
logP -3.1 Not Available
Predicted Properties
Property Value Source
water solubility 2.25e-01 g/l ALOGPS
logP 1.11 ALOGPS
logP -4.4 ChemAxon
logS -3.8 ALOGPS
pKa (strongest acidic) 2.99 ChemAxon
pKa (strongest basic) 9.93 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 24 ChemAxon
hydrogen donor count 19 ChemAxon
polar surface area 530.49 ChemAxon
rotatable bond count 13 ChemAxon
refractivity 346.61 ChemAxon
polarizability 138.7 ChemAxon
References
Synthesis Reference
  1. Boger DL. Vancomycin, teicoplanin, and ramoplanin: synthetic and mechanistic studies. Med Res Rev. 2001 Sep;21(5):356-81. Pubmed
General Reference
  1. Schäfer, Martina, Thomas R Schneider, and George M Sheldrick. 1996. Crystal structure of vancomycin. Structure 4, no. 12 (December 15): 1509-1515. DOI:10.1016/S0969-2126(96)00156-6.
  2. Levine DP: Vancomycin: a history. Clin Infect Dis. 2006 Jan 1;42 Suppl 1:S5-12. Pubmed
  3. Small PM, Chambers HF: Vancomycin for Staphylococcus aureus endocarditis in intravenous drug users. Antimicrob Agents Chemother. 1990 Jun;34(6):1227-31. Pubmed
  4. Gonzalez C, Rubio M, Romero-Vivas J, Gonzalez M, Picazo JJ: Bacteremic pneumonia due to Staphylococcus aureus: A comparison of disease caused by methicillin-resistant and methicillin-susceptible organisms. Clin Infect Dis. 1999 Nov;29(5):1171-7. Pubmed
  5. Sivagnanam S, Deleu D: Red man syndrome. Crit Care. 2003 Apr;7(2):119-20. Epub 2002 Dec 23. Pubmed
  6. Cantu TG, Yamanaka-Yuen NA, Lietman PS: Serum vancomycin concentrations: reappraisal of their clinical value. Clin Infect Dis. 1994 Apr;18(4):533-43. Pubmed
External Links
Resource Link
KEGG Drug D00212 Link_out
KEGG Compound C06689 Link_out
PubChem Compound 14969 Link_out
PubChem Substance 46505261 Link_out
ChemSpider 389935 Link_out
ChEBI 28001 Link_out
ChEMBL 28001 Link_out
Therapeutic Targets Database DAP001330 Link_out
PharmGKB PA451850 Link_out
HET DVV Link_out
Drug Product Database 2241807 Link_out
RxList http://www.rxlist.com/cgi/generic2/vancomycin.htm Link_out
Drugs.com http://www.drugs.com/vancomycin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Vancomycin Link_out
ATC Codes
  • A07AA09
  • J01XA01
AHFS Codes
  • 08:12.28.16
PDB Entries
FDA label show (57.8 KB)
MSDS show (73 KB)
Interactions
Drug Interactions
Drug Interaction
Colistimethate Additive nephrotoxic effects may occur. Consider alternate therapy or monitor for renal function during concomitant therapy.
Gallium nitrate Additive nephrotoxic effects may occur. Avoid concomitant therapy.
Tobramycin Increased risk of nephrotoxicity
Food Interactions Not Available
Targets

1. D-Ala-D-Ala moiety of NAM/NAG peptide subunits of peptidoglycan

Pharmacological action: yes
Actions: inhibitor

References:
  1. Reynolds PE: Structure, biochemistry and mechanism of action of glycopeptide antibiotics. Eur J Clin Microbiol Infect Dis. 1989 Nov;8(11):943-50. Pubmed
  2. Reynolds PE, Somner EA: Comparison of the target sites and mechanisms of action of glycopeptide and lipoglycodepsipeptide antibiotics. Drugs Exp Clin Res. 1990;16(8):385-9. Pubmed
  3. Boger DL: Vancomycin, teicoplanin, and ramoplanin: synthetic and mechanistic studies. Med Res Rev. 2001 Sep;21(5):356-81. Pubmed

2. Glycosyltransferase GtfA

Pharmacological action: no
Actions: other
Organism class: bacterial
UniProt ID: P96558 Link_out
Gene: gtfA
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mulichak AM, Lu W, Losey HC, Walsh CT, Garavito RM: Crystal structure of vancosaminyltransferase GtfD from the vancomycin biosynthetic pathway: interactions with acceptor and nucleotide ligands. Biochemistry. 2004 May 11;43(18):5170-80. Pubmed
Transporters

1. Solute carrier family 22 member 6

Actions: inhibitor
UniProt ID: Q4U2R8 Link_out
Gene: hROAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19