Colistin

Identification

Name
Colistin
Accession Number
DB00803  (APRD00886)
Type
Small Molecule
Groups
Approved
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.

Structure
Thumb
Synonyms
  • Colistin
  • Colistina
  • Colistine
  • Colistinum
  • Polymyxin E
Product Ingredients
IngredientUNIICASInChI Key
Colistin sulfateWP15DXU5771264-72-8ZJIWRHLZXQPFAD-LRYSGCCDSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Colistimethate for InjectionPowder, for solution150 mgIntramuscular; IntravenousFresenius Kabi2014-06-05Not applicableCanada
Colistimethate for Injection U.S.P.Powder, for solution150 mgIntramuscular; IntravenousSterimax Inc2002-04-15Not applicableCanada
Coly-mycin M ParenteralPowder, for solution150 mgIntramuscular; IntravenousErfa Canada 2012 Inc1974-12-31Not applicableCanada
International/Other Brands
Alfacolin (Catalysis) / Alficetin (Nova Argentia) / ColiFin (Pari Pharma) / Colimicina (Quimifar) / Colimycine (Sanofi Aventis) / Coliracin (Rafa) / Colistate (Atlantic Lab) / Colomycin (Forest) / Coly-Mycin (King Pharmaceuticals) / Diarönt mono (CNP) / Promixin (Profile Pharma) / Tadim (Allertec) / Walamycin (Wallace)
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Coly-Mycin SColistin sulfate (3 mg/mL) + Hydrocortisone acetate (10 mg/mL) + Neomycin sulfate (3.3 mg/mL) + Thonzonium (.5 mg/mL)SuspensionAuricular (otic)Par Pharmaceutical2007-11-012017-06-18Us
Coly-Mycin SColistin sulfate (3 mg/mL) + Hydrocortisone acetate (10 mg/mL) + Neomycin sulfate (3.3 mg/mL) + Thonzonium bromide (.5 mg/mL)SuspensionAuricular (otic)Endo Pharmaceuticals2016-04-18Not applicableUs
Cortisporin-TCColistin sulfate (3 mg/mL) + Hydrocortisone acetate (10 mg/mL) + Neomycin sulfate (3.3 mg/mL) + Thonzonium (.5 mg/mL)SuspensionAuricular (otic)Par Pharmaceutical2007-11-01Not applicableUs
Cortisporin-TCColistin sulfate (3 mg/mL) + Hydrocortisone acetate (10 mg/mL) + Neomycin sulfate (3.3 mg/mL) + Thonzonium (.5 mg/mL)SuspensionAuricular (otic)Physicians Total Care, Inc.2007-05-07Not applicableUs
Categories
UNII
Z67X93HJG1
CAS number
1066-17-7
Weight
Average: 1155.455
Monoisotopic: 1154.74992728
Chemical Formula
C52H98N16O13
InChI Key
YKQOSKADJPQZHB-BRLOSWAASA-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-{[(6R,9S,12R,18S,21S)-6,9,18-tris(2-aminoethyl)-2,5,8,11,14,17,20-heptahydroxy-3-[(1R)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-1,4,7,10,13,16,19-heptaazacyclotricosa-1,4,7,10,13,16,19-heptaen-21-yl]-C-hydroxycarbonimidoyl}propyl]-C-hydroxycarbonimidoyl}-2-hydroxypropyl]-C-hydroxycarbonimidoyl}propyl]-5-methylheptanimidic acid
SMILES
[H]C(C)(CC)CCCC(O)=N[[email protected]@]([H])(CCN)C(O)=N[[email protected]]([H])(C(O)=N[[email protected]@]([H])(CCN)C(O)=N[[email protected]@]1([H])CCN=C(O)C([H])(N=C(O)[[email protected]@]([H])(CCN)N=C(O)[[email protected]]([H])(CCN)N=C(O)[[email protected]@]([H])(CC(C)C)N=C(O)C([H])(CC(C)C)N=C(O)[[email protected]]([H])(CCN)N=C1O)[[email protected]@]([H])(C)O)[[email protected]@]([H])(C)O

Pharmacology

Indication

For the treatment of acute or chronic infections due to sensitive strains of certain gram-negative bacilli, particularly Pseudomonas aeruginosa.

Structured Indications
Pharmacodynamics

Colistin 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 action

Colistin 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.

TargetActionsOrganism
ABacterial outer membrane
incorporation into and destabilization
Absorption

Very poor absorption from gastrointestinal tract.

Volume of distribution
Not Available
Protein binding
Not 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 elimination
Not Available
Half life

5 hours

Clearance
Not Available
Toxicity

Oral 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Colistin.Investigational
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Colistin.Approved
Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Drug
D02138
KEGG Compound
C13768
PubChem Compound
131704173
PubChem Substance
46505467
ChEMBL
CHEMBL407135
Therapeutic Targets Database
DAP001324
PharmGKB
PA164760862
Wikipedia
Colistin
ATC Codes
A07AA10 — ColistinJ01XB01 — Colistin
AHFS Codes
  • 08:12.28.28 — Polymyxins
MSDS
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Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
1Active Not RecruitingTreatmentInfections, Pneumococcal / Pathogen Resistance / Pneumonia1
2Active Not RecruitingTreatmentIntestinal Colonization With Multidrug-resistant Bacteria1
2CompletedTreatmentCystic Fibrosis (CF) / Pseudomonas Aeruginosa1
2, 3Unknown StatusPreventionBacteremia / Bacteremia Associated With Intravascular Line / Ventilator-associated Bacterial Pneumonia1
3CompletedTreatmentAcute Pyelonephritis (AP) Due to CRE / Bloodstream Infections (BSI) Due to CRE / Complicated Urinary Tract Infection (cUTI) Due to CRE / Hospital-Acquired Bacterial Pneumonia (HABP) Due to CRE / Ventilator-Associated Bacterial Pneumonia (VABP) Due to CRE1
3CompletedTreatmentCystic Fibrosis With Pulmonary Manifestations1
3CompletedTreatmentHospital-acquired bacterial pneumonia / Infection Due to Resistant Bacteria / Infection of Bloodstream / Infectious Disease of Abdomen / Ventilator-Associated Pneumonia (VAP)1
3CompletedTreatmentVentilator-associated Bacterial Pneumonia1
3RecruitingPreventionCritical Illness / Sepsis / Shock, Septic / Ventilator-associated Bacterial Pneumonia1
3RecruitingPreventionNon Cystic Fibrosis Bronchiectasis1
3RecruitingTreatmentBlood Stream Infections / Pneumonia1
3RecruitingTreatmentColistin Adverse Reaction / Infection Due to Multidrug Resistant Acinetobacter / Infection Resistant to Multiple Drugs / Ventilator-Associated Pneumonia (VAP)1
3Unknown StatusPreventionDrug Safety1
3Unknown StatusTreatmentCross Infection / Pneumonia, Bacterial1
3Unknown StatusTreatmentDrug Safety2
3Unknown StatusTreatmentInfection NOS1
4CompletedPreventionHematological Infection1
4CompletedTreatmentGram-Negative Bacterial Infections1
4CompletedTreatmentVentilator-Associated Pneumonia (VAP)1
4RecruitingTreatmentBronchiectasis1
4RecruitingTreatmentColistin / Colistin Adverse Reaction / Gram-Negative Bacterial Infections / MIC / Pediatric Cancer1
4RecruitingTreatmentCystic Fibrosis (CF)1
4RecruitingTreatmentGram Negative Bacterial Infections1
4RecruitingTreatmentInfectious Diseases1
4Unknown StatusTreatmentInfection NOS1
Not AvailableActive Not RecruitingNot AvailableColistin1
Not AvailableCompletedNot AvailableAcinetobacter Infections1
Not AvailableCompletedNot AvailableSepsis1
Not AvailableCompletedPreventionPneumonia / Tracheobronchitis1
Not AvailableRecruitingNot AvailableAcinetobacter Infections1
Not AvailableRecruitingDiagnosticCystic Fibrosis (CF)1

Pharmacoeconomics

Manufacturers
  • Parke davis div warner lambert co
Packagers
Dosage forms
FormRouteStrength
Powder, for solutionIntramuscular; Intravenous150 mg
SuspensionAuricular (otic)
Prices
Unit descriptionCostUnit
Colistin sulfate powder513.26USD each
Coly-Mycin S 3.3-3-10 mg/ml Suspension 5ml Bottle49.17USD bottle
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)200-220 °CNot Available
water solubility5.64E+005 mg/LNot Available
logP-2.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0799 mg/mLALOGPS
logP0.22ALOGPS
logP0.92ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)2.69ChemAxon
Physiological Charge5ChemAxon
Hydrogen Acceptor Count29ChemAxon
Hydrogen Donor Count18ChemAxon
Polar Surface Area529.05 Å2ChemAxon
Rotatable Bond Count28ChemAxon
Refractivity303.41 m3·mol-1ChemAxon
Polarizability0 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7444
Blood Brain Barrier-0.9752
Caco-2 permeable-0.7492
P-glycoprotein substrateSubstrate0.8048
P-glycoprotein inhibitor INon-inhibitor0.7514
P-glycoprotein inhibitor IINon-inhibitor0.8582
Renal organic cation transporterNon-inhibitor0.9525
CYP450 2C9 substrateNon-substrate0.893
CYP450 2D6 substrateNon-substrate0.7907
CYP450 3A4 substrateNon-substrate0.513
CYP450 1A2 substrateNon-inhibitor0.9372
CYP450 2C9 inhibitorNon-inhibitor0.9387
CYP450 2D6 inhibitorNon-inhibitor0.929
CYP450 2C19 inhibitorNon-inhibitor0.9139
CYP450 3A4 inhibitorNon-inhibitor0.8879
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9937
Ames testNon AMES toxic0.8807
CarcinogenicityNon-carcinogens0.8947
BiodegradationNot ready biodegradable0.9515
Rat acute toxicity3.0728 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9855
hERG inhibition (predictor II)Non-inhibitor0.8646
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as cyclic peptides. These are compounds containing a cyclic moiety bearing a peptide backbone.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Cyclic peptides
Alternative Parents
Cyclic carboximidic acids / Secondary alcohols / Propargyl-type 1,3-dipolar organic compounds / Polyols / Azacyclic compounds / Organopnictogen compounds / Monoalkylamines / Hydrocarbon derivatives
Substituents
Cyclic alpha peptide / Cyclic carboximidic acid / Secondary alcohol / Carboximidic acid / Carboximidic acid derivative / Polyol / Propargyl-type 1,3-dipolar organic compound / Organic 1,3-dipolar compound / Organoheterocyclic compound / Azacycle
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

1. Bacterial outer membrane
Kind
Group
Organism
Not Available
Pharmacological action
Yes
Actions
Incorporation into and destabilization
References
  1. Vaara M: Polymyxins and their novel derivatives. Curr Opin Microbiol. 2010 Oct;13(5):574-81. doi: 10.1016/j.mib.2010.09.002. Epub 2010 Sep 24. [PubMed:20869908]
  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. doi: 10.1093/jac/dkq422. Epub 2010 Nov 16. [PubMed:21081544]
  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:10492501]

Drug created on June 13, 2005 07:24 / Updated on January 15, 2018 08:47