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Identification
NameColistin
Accession NumberDB00803  (APRD00886)
Typesmall molecule
Groupsapproved
Description

Cyclic polypeptide antibiotic from Bacillus colistinus. It is composed of Polymyxins E1 and E2 (or Colistins A, B, and C) which act as detergents on cell membranes. Colistin is less toxic than Polymyxin B, but otherwise similar; the methanesulfonate is used orally. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
ColistinGermanINN
ColistinaSpanishINN
ColistineFrenchINN
ColistinumLatinINN
Polymyxin ENot AvailableIS
Salts
Name/CAS Structure Properties
Colistin Sodium Methansulfonate
Thumb Not applicable DBSALT000944
Colistin sulfate
Thumb Not applicable DBSALT000691
Brand names
NameCompany
AlfacolinCatalysis
AlficetinNova Argentia
ColiFinPari Pharma
ColimicinaQuimifar
ColimycineSanofi Aventis
ColiracinRafa
ColistateAtlantic Lab
ColistimethateSteriMax
ColomycinForest
Coly-MycinKing Pharmaceuticals
Diarönt monoCNP
PromixinProfile Pharma
TadimAllertec
WalamycinWallace
Brand mixtures
Brand NameIngredients
Colimy CColistin and Chloramphenicol
Colimy FoamColistin and Neomycin
Colimycin TColistin and Tetracycline
SulopredColistin and Erythromycin
Categories
CAS number1264-72-8
WeightAverage: 1155.4339
Monoisotopic: 1154.749927302
Chemical FormulaC52H98N16O13
InChI KeyInChIKey=YKQOSKADJPQZHB-QNPLFGSASA-N
InChI
InChI=1S/C52H98N16O13/c1-9-29(6)11-10-12-40(71)59-32(13-19-53)47(76)68-42(31(8)70)52(81)64-35(16-22-56)44(73)63-37-18-24-58-51(80)41(30(7)69)67-48(77)36(17-23-57)61-43(72)33(14-20-54)62-49(78)38(25-27(2)3)66-50(79)39(26-28(4)5)65-45(74)34(15-21-55)60-46(37)75/h27-39,41-42,69-70H,9-26,53-57H2,1-8H3,(H,58,80)(H,59,71)(H,60,75)(H,61,72)(H,62,78)(H,63,73)(H,64,81)(H,65,74)(H,66,79)(H,67,77)(H,68,76)/t29?,30-,31-,32+,33+,34+,35+,36+,37+,38+,39-,41+,42+/m1/s1
IUPAC Name
N-[(1S)-3-amino-1-{[(1S,2R)-1-{[(1S)-3-amino-1-{[(3S,6S,9S,12S,15R,18S,21S)-6,9,18-tris(2-aminoethyl)-3-[(1R)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptaazacyclotricosan-21-yl]carbamoyl}propyl]carbamoyl}-2-hydroxypropyl]carbamoyl}propyl]-5-methylheptanamide
SMILES
[H][C@]1(NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC(=O)[C@H](CCNC1=O)NC(=O)[C@H](CCN)NC(=O)[C@@H](NC(=O)[C@H](CCN)NC(=O)CCCC(C)CC)[C@@H](C)O)[C@@H](C)O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids and Derivatives
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentCyclic Peptides
Alternative parentsN-acyl-alpha Amino Acids and Derivatives; Alpha Amino Acid Amides; N-acyl Amines; Secondary Carboxylic Acid Amides; Secondary Alcohols; Polyamines; Enolates; Carboxylic Acids; Monoalkylamines
Substituentsn-acyl-alpha amino acid or derivative; alpha-amino acid amide; n-acyl-amine; alpha-amino acid or derivative; carboxamide group; secondary alcohol; secondary carboxylic acid amide; enolate; carboxylic acid; polyamine; amine; primary amine; alcohol; primary aliphatic amine; organonitrogen compound
Classification descriptionThis compound belongs to the cyclic peptides. These are compounds containing a cyclic moiety bearing a peptide backbone.
Pharmacology
IndicationFor the treatment of acute or chronic infections due to sensitive strains of certain gram-negative bacilli, particularly Pseudomonas aeruginosa.
PharmacodynamicsColistin is a polymyxin antibiotic agent. Polymyxins are cationic polypeptides that disrupt the bacterial cell membrane through a detergentlike mechanism. With the development of less toxic agents, such as extended-spectrum penicillins and cephalosporins, parenteral polymyxin use was largely abandoned, except for the treatment of multidrug-resistant pulmonary infections in patients with cystic fibrosis. More recently, however, the emergence of multidrug-resistant gram-negative bacteria, such as Pseudomonas aeruginosa and Acinetobacter baumannii, and the lack of new antimicrobial agents have led to the revived use of the polymyxins.
Mechanism of actionColistin is a surface active agent which penetrates into and disrupts the bacterial cell membrane. Colistin is polycationic and has both hydrophobic and lipophilic moieties. It interacts with the bacterial cytoplasmic membrane, changing its permeability. This effect is bactericidal. There is also evidence that polymyxins enter the cell and precipitate cytoplasmic components, primarily ribosomes.
AbsorptionVery poor absorption from gastrointestinal tract.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

As 80% of the dose can be recovered unchanged in the urine, and there is no biliary excretion, it can be assumed that the remaining drug is inactivated in the tissues, however the mechanism is unknown.

Route of eliminationNot Available
Half life5 hours
ClearanceNot Available
ToxicityOral LD50 in rats is 5450 mg/kg. Overdosage with colistimethate can cause neuromuscular blockade characterized by paresthesia, lethargy, confusion, dizziness, ataxia, nystagmus, disorders of speech and apnea. Respiratory muscle paralysis may lead to apnea, respiratory arrest and death.
Affected organisms
  • Gram-negative bacilli
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.7444
Blood Brain Barrier - 0.9752
Caco-2 permeable - 0.7492
P-glycoprotein substrate Substrate 0.8048
P-glycoprotein inhibitor I Non-inhibitor 0.7514
P-glycoprotein inhibitor II Non-inhibitor 0.8582
Renal organic cation transporter Non-inhibitor 0.9525
CYP450 2C9 substrate Non-substrate 0.893
CYP450 2D6 substrate Non-substrate 0.7907
CYP450 3A4 substrate Non-substrate 0.513
CYP450 1A2 substrate Non-inhibitor 0.9372
CYP450 2C9 substrate Non-inhibitor 0.9387
CYP450 2D6 substrate Non-inhibitor 0.929
CYP450 2C19 substrate Non-inhibitor 0.9139
CYP450 3A4 substrate Non-inhibitor 0.8879
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9937
Ames test Non AMES toxic 0.8807
Carcinogenicity Non-carcinogens 0.8947
Biodegradation Not ready biodegradable 0.9515
Rat acute toxicity 3.0728 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9855
hERG inhibition (predictor II) Non-inhibitor 0.8646
Pharmacoeconomics
Manufacturers
  • Parke davis div warner lambert co
Packagers
Dosage forms
FormRouteStrength
Powder, for solutionIntravenous
Prices
Unit descriptionCostUnit
Colistin sulfate powder513.26USDeach
Coly-Mycin S 3.3-3-10 mg/ml Suspension 5ml Bottle49.17USDbottle
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point200-220 °CNot Available
water solubility5.64E+005 mg/LNot Available
logP-2.4Not Available
Predicted Properties
PropertyValueSource
water solubility2.38e-01 g/lALOGPS
logP-1.3ALOGPS
logP-8.1ChemAxon
logS-3.7ALOGPS
pKa (strongest acidic)11.6ChemAxon
pKa (strongest basic)10.23ChemAxon
physiological charge5ChemAxon
hydrogen acceptor count18ChemAxon
hydrogen donor count18ChemAxon
polar surface area490.66ChemAxon
rotatable bond count28ChemAxon
refractivity297.67ChemAxon
polarizability125.93ChemAxon
number of rings1ChemAxon
bioavailability0ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD02138
KEGG CompoundC13768
PubChem Compound5311054
PubChem Substance46505467
ChemSpider4470591
Therapeutic Targets DatabaseDAP001324
PharmGKBPA164760862
WikipediaColistin
ATC CodesJ01XB01A07AA10
AHFS Codes
  • 08:12.28.28
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(72.2 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

1. Bacterial outer membrane

Kind: group

Organism:

Pharmacological action: yes

Actions: incorporation into and destabilization

Components

Name UniProt ID Details

References:

  1. Vaara M: Polymyxins and their novel derivatives. Curr Opin Microbiol. 2010 Oct;13(5):574-81. Epub 2010 Sep 24. Pubmed
  2. Soon RL, Nation RL, Cockram S, Moffatt JH, Harper M, Adler B, Boyce JD, Larson I, Li J: Different surface charge of colistin-susceptible and -resistant Acinetobacter baumannii cells measured with zeta potential as a function of growth phase and colistin treatment. J Antimicrob Chemother. 2011 Jan;66(1):126-33. Epub 2010 Nov 16. Pubmed
  3. Evans ME, Feola DJ, Rapp RP: Polymyxin B sulfate and colistin: old antibiotics for emerging multiresistant gram-negative bacteria. Ann Pharmacother. 1999 Sep;33(9):960-7. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12