Colistin

Identification

Summary

Colistin is a polymyxin antibiotic used to treat bacterial infections caused by susceptible Gram negative bacteria.

Brand Names
Cortisporin-TC
Generic Name
Colistin
DrugBank Accession Number
DB00803
Background

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.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 1155.455
Monoisotopic: 1154.74992728
Chemical Formula
C52H98N16O13
Synonyms
  • Colimycin
  • Colistin
  • Colistina
  • Colistine
  • Colistinum
  • Kolimycin
  • Polymyxin E

Pharmacology

Indication

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

Pharmacology
Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
Avoid life-threatening adverse drug events
Improve clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events & improve clinical decision support.
Learn more
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
Bacteria
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

Adverse Effects
Adverseeffects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.
Learn more
Improve decision support & research outcomes with our structured adverse effects data.
Learn more
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.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirAbacavir may decrease the excretion rate of Colistin which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Colistin which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Colistin which could result in a higher serum level.
AcenocoumarolThe risk or severity of bleeding can be increased when Colistin is combined with Acenocoumarol.
AcetaminophenAcetaminophen may decrease the excretion rate of Colistin which could result in a higher serum level.
AcetylcholineThe therapeutic efficacy of Acetylcholine can be decreased when used in combination with Colistin.
AcetyldigitoxinThe risk or severity of adverse effects can be increased when Colistin is combined with Acetyldigitoxin.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Colistin which could result in a higher serum level.
AclidiniumAclidinium may decrease the excretion rate of Colistin which could result in a higher serum level.
AcrivastineAcrivastine may decrease the excretion rate of Colistin which could result in a higher serum level.
Interactions
Identify potential medication risks
Easily compare up to 40 drugs with our drug interaction checker.
Get severity rating, description, and management advice.
Learn more
Food Interactions
No interactions found.

Products

Products2
Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Colistin sulfateWP15DXU5771264-72-8ZJIWRHLZXQPFAD-LRYSGCCDSA-N
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 EndRegionImage
Coly-Mycin SColistin sulfate (3 mg/1mL) + Hydrocortisone acetate (10 mg/1mL) + Neomycin sulfate (3.3 mg/1mL) + Thonzonium bromide (0.5 mg/1mL)SuspensionAuricular (otic)Par Pharmaceutical2007-11-012017-06-18US flag
Coly-Mycin SColistin sulfate (3 mg/1mL) + Hydrocortisone acetate (10 mg/1mL) + Neomycin sulfate (3.3 mg/1mL) + Thonzonium bromide (0.5 mg/1mL)SuspensionAuricular (otic)Endo Pharmaceuticals Inc.2016-04-182020-04-30US flag
Coly-Mycin SColistin sulfate (3 mg/1mL) + Hydrocortisone acetate (10 mg/1mL) + Neomycin sulfate (3.3 mg/1mL) + Thonzonium bromide (0.5 mg/1mL)SuspensionAuricular (otic)Physicians Total Care, Inc.2007-11-012012-06-30US flag
Cortisporin TCColistin sulfate (3 mg/1mL) + Hydrocortisone acetate (10 mg/1mL) + Neomycin sulfate (3.3 mg/1mL) + Thonzonium bromide (0.5 mg/1mL)SuspensionAuricular (otic)Endo Pharmaceuticals, Inc.2019-06-03Not applicableUS flag
Cortisporin-TCColistin sulfate (3 mg/1mL) + Hydrocortisone acetate (10 mg/1mL) + Neomycin sulfate (3.3 mg/1mL) + Thonzonium bromide (0.5 mg/1mL)SuspensionAuricular (otic)Physicians Total Care, Inc.2007-05-07Not applicableUS flag
Cortisporin-TCColistin sulfate (3 mg/1mL) + Hydrocortisone acetate (10 mg/1mL) + Neomycin sulfate (3.3 mg/1mL) + Thonzonium bromide (0.5 mg/1mL)SuspensionAuricular (otic)Par Pharmaceutical, Inc.2007-11-012017-05-30US flag
FIXAMICIN® GOTAS OTICASColistin sulfate (1.538 mg) + Hydrocortisone (0.5 mg) + Neomycin (5 mg)SuspensionAuricular (otic)TECNOFAR TQ S.A.S2011-08-29Not applicableColombia flag

Categories

ATC Codes
J01XB01 — ColistinA07AA10 — Colistin
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Alcohol / Aliphatic heteromonocyclic compound / Amine / Azacycle / Carboximidic acid / Carboximidic acid derivative / Cyclic alpha peptide / Cyclic carboximidic acid / Hydrocarbon derivative / Organic 1,3-dipolar compound
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
Not Available
Affected organisms
  • Gram-negative bacilli

Chemical Identifiers

UNII
Z67X93HJG1
CAS number
1066-17-7
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,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
CCC(C)CCCC(=O)N[C@@H](CCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)C(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)NC1=O)[C@@H](C)O

References

General References
Not Available
KEGG Drug
D02138
KEGG Compound
C13768
PubChem Compound
131704173
PubChem Substance
46505467
RxNav
2709
ChEMBL
CHEMBL407135
Therapeutic Targets Database
DAP001324
PharmGKB
PA164760862
Wikipedia
Colistin
MSDS
Download (72.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentCystic Fibrosis (CF)1
4CompletedPreventionHematological Infection1
4CompletedTreatmentBronchiectasis1
4CompletedTreatmentColistin / Colistin Adverse Reaction / Gram-Negative Bacterial Infections / MIC / Pediatrics Cancer1
4CompletedTreatmentCystic Fibrosis (CF)1
4CompletedTreatmentGram-Negative Bacterial Infections1
4CompletedTreatmentVentilator Associated Bacterial Pneumonia1
4RecruitingTreatmentCritically Ill Patients / Infections, Hospital / Multi-antibiotic Resistance1
4RecruitingTreatmentTreatment of Blood Stream Infections Due to Multidrug-Resistant Klebsiella Pneumoniae1
4TerminatedSupportive CareColorectal Carcinoma (CRC)1

Pharmacoeconomics

Manufacturers
  • Parke davis div warner lambert co
Packagers
  • Paddock Labs
Dosage Forms
FormRouteStrength
Powder, for solutionOral100 mg/g
Injection, powder, for solution1000000 UI/4ML
Solution / dropsOral4000000 U/3.5ML
Tablet1500.000 U
GranuleOral10 %
Injection, powder, for solution1000.000 U.I.
GranuleOral
Tablet
Powder, for solutionOral150 MIU
Powder, for solutionOral75 mg/g
SuspensionAuricular (otic)
Powder
SolutionOral
Powder, for solutionOral
Injection, powder, for solution
Injection, powder, for solution1000.000 UI
Injection, powder, for solution2000.000 UI
GranuleOral10 % w/w
SolutionOral2.4 MIU/ML
Powder, for solutionOral2 MIU/G
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 Solubility0.238 mg/mLALOGPS
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 Area490.66 Å2ChemAxon
Rotatable Bond Count28ChemAxon
Refractivity297.67 m3·mol-1ChemAxon
Polarizability123.32 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

Targets

Drugtargets2
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
1. Bacterial outer membrane
Kind
Group
Organism
Bacteria
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. [Article]
  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. [Article]
  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. [Article]

Drug created on June 13, 2005 13:24 / Updated on October 20, 2021 19:48