Colistimethate

Identification

Name
Colistimethate
Accession Number
DB01111  (APRD00885)
Type
Small Molecule
Groups
Approved, Vet approved
Description

Colistimethate is an antibiotic that has been shown to have bactericidal activity against aerobic gram-negative microorganisms. Colistimethate is particularly indicated when the infection is caused by sensitive strains of Pseudomonas aeruginosa.

Structure
Thumb
Synonyms
  • Colistin methanesulfonic acid
  • Colistin sulfomethate
  • Colistinmethanesulfonic acid
Product Ingredients
IngredientUNIICASInChI Key
Colistimethate sodiumXW0E5YS77G8068-28-8IQWHCHZFYPIVRV-UHFFFAOYSA-I
Active Moieties
NameKindUNIICASInChI Key
ColistinprodrugZ67X93HJG11066-17-7YKQOSKADJPQZHB-BRLOSWAASA-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
ColobreatheCapsule1662500 IURespiratory (inhalation)Teva B.V.2012-02-13Not applicableEu
ColobreatheCapsule1662500 IURespiratory (inhalation)Teva B.V.2012-02-13Not applicableEu
ColobreatheCapsule1662500 IURespiratory (inhalation)Teva B.V.2012-02-13Not applicableEu
Coly-Mycin MInjection, powder, lyophilized, for solution150 mg/2mLIntramuscular; IntravenousMonarch Pharmaceuticals,Inc1970-06-042007-10-01Us
Coly-Mycin MInjection150 mg/2mLIntramuscular; IntravenousPar Pharmaceutical2007-11-01Not applicableUs
Coly-mycin M ParenteralPowder, for solution150 mgIntramuscular; IntravenousErfa Canada 2012 Inc1974-12-31Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ColistimethateInjection, powder, lyophilized, for solution150 mg/2mLIntramuscular; IntravenousFresenius Kabi2009-12-04Not applicableUs
ColistimethateInjection, powder, for solution150 mg/1Intramuscular; IntravenousXellia Pharmaceuticals USA LLC2018-10-01Not applicableUs
ColistimethateInjection150 mg/2mLIntramuscular; IntravenousXellia Pharmaceuticals ApS2012-11-22Not applicableUs
ColistimethateInjection, powder, lyophilized, for solution150 mg/2mLIntramuscular; IntravenousPaddock Laboratories, Inc.2014-04-152018-06-30Us
ColistimethateInjection150 mg/2mLIntramuscular; IntravenousPar Pharmaceutical2012-06-01Not applicableUs
ColistimethateInjection150 mg/2mLIntramuscular; IntravenousX Gen Pharmaceuticals, Inc.2016-07-01Not applicableUs
ColistimethateInjection, powder, lyophilized, for solution150 mg/2mLIntramuscular; IntravenousX Gen Pharmaceuticals, Inc.2011-01-01Not applicableUs
ColistimethateInjection, powder, lyophilized, for solution150 mg/2mLIntramuscular; IntravenousSagent Pharmaceuticals2014-12-29Not applicableUs
Colistimethate SodiumInjection, powder, lyophilized, for solution150 mg/4mLIntramuscular; IntravenousHeritage2012-10-22Not applicableUs
Categories
UNII
DL2R53P963
CAS number
12705-41-8
Weight
Average: 1634.87
Monoisotopic: 1633.588775306
Chemical Formula
C58H105N16O28S5
InChI Key
BSSIRFLGSWHWDE-UHFFFAOYSA-I
InChI
InChI=1S/C58H110N16O28S5/c1-9-35(6)12-10-11-13-46(77)65-38(14-20-59-28-103(88,89)90)53(82)74-48(37(8)76)58(87)70-41(17-23-62-31-106(97,98)99)50(79)68-43-19-25-64-57(86)47(36(7)75)73-54(83)42(18-24-63-32-107(100,101)102)67-49(78)39(15-21-60-29-104(91,92)93)69-55(84)44(26-33(2)3)72-56(85)45(27-34(4)5)71-52(81)40(66-51(43)80)16-22-61-30-105(94,95)96/h33-45,47-48,59-63,75-76H,9-32H2,1-8H3,(H,64,86)(H,65,77)(H,66,80)(H,67,78)(H,68,79)(H,69,84)(H,70,87)(H,71,81)(H,72,85)(H,73,83)(H,74,82)(H,88,89,90)(H,91,92,93)(H,94,95,96)(H,97,98,99)(H,100,101,102)/p-5
IUPAC Name
[(3-{3-hydroxy-2-[2-(6-methyloctanamido)-4-[(sulfonatomethyl)amino]butanamido]butanamido}-3-{[3-(1-hydroxyethyl)-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-6,9,18-tris({2-[(sulfonatomethyl)amino]ethyl})-1,4,7,10,13,16,19-heptaazacyclotricosan-21-yl]carbamoyl}propyl)amino]methanesulfonate
SMILES
CCC(C)CCCCC(=O)NC(CCNCS([O-])(=O)=O)C(=O)NC(C(C)O)C(=O)NC(CCNCS([O-])(=O)=O)C(=O)NC1CCNC(=O)C(NC(=O)C(CCNCS([O-])(=O)=O)NC(=O)C(CCNCS([O-])(=O)=O)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCNCS([O-])(=O)=O)NC1=O)C(C)O

Pharmacology

Indication

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

Associated Conditions
Pharmacodynamics

Colistimethate is a polymyxin antibiotic agent. Originally, colistimethate sodium was thought to be less toxic than polymyxin B; however, if the drugs are administered at comparable doses, their toxicities may be similar. 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

Colistimethate is a surface active agent which penetrates into and disrupts the bacterial cell membrane. Colistimethate 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

2-3 hours following either intravenous or intramuscular administration in adults and in the pediatric population, including premature infants.

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
DrugInteraction
AcetaminophenColistimethate may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Colistimethate.
Acetylsalicylic acidThe risk or severity of nephrotoxicity can be increased when Colistimethate is combined with Acetylsalicylic acid.
AcyclovirColistimethate may decrease the excretion rate of Acyclovir which could result in a higher serum level.
Adefovir DipivoxilThe risk or severity of nephrotoxicity can be increased when Colistimethate is combined with Adefovir Dipivoxil.
AlcuroniumColistimethate may increase the neuromuscular blocking activities of Alcuronium.
Alendronic acidThe risk or severity of nephrotoxicity and hypocalcemia can be increased when Colistimethate is combined with Alendronic acid.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Colistimethate.
AlimemazineThe risk or severity of adverse effects can be increased when Alimemazine is combined with Colistimethate.
AlmotriptanThe risk or severity of adverse effects can be increased when Colistimethate is combined with Almotriptan.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015243
PubChem Compound
70789202
PubChem Substance
46508586
ChemSpider
26329515
ChEBI
59662
Therapeutic Targets Database
DAP001329
PharmGKB
PA164749509
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Colistimethate
AHFS Codes
  • 08:12.28.28 — Polymyxins
FDA label
Download (66.2 KB)
MSDS
Download (50.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentPseudomonas Infections1
2Unknown StatusTreatmentPneumonia, Hospital-Acquired1
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
3CompletedTreatmentBacterial Infections1
3RecruitingPreventionNon Cystic Fibrosis Bronchiectasis2
3RecruitingTreatmentBlood Stream Infections / Pneumonia1
3TerminatedTreatmentColistin Adverse Reaction / Infection Due to Multidrug Resistant Acinetobacter / Infection Resistant to Multiple Drugs / Ventilator-Associated Pneumonia (VAP)1
4CompletedPreventionHematological Infection1
4CompletedTreatmentCystic Fibrosis (CF)1
4CompletedTreatmentGram-Negative Bacterial Infections1
4RecruitingTreatmentColistin / Colistin Adverse Reaction / Gram-Negative Bacterial Infections / MIC / Pediatric Cancer1
4RecruitingTreatmentGram Negative Bacterial Infections1
Not AvailableActive Not RecruitingNot AvailableColistin1
Not AvailableCompletedNot AvailableAcinetobacter Infections1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • APP Pharmaceuticals
  • Ben Venue Laboratories Inc.
  • Draxis Specialty Pharmaceuticals Inc.
  • JHP Pharmaceuticals LLC
  • Monarch Pharmacy
  • Paddock Labs
  • X-Gen Pharmaceuticals
Dosage forms
FormRouteStrength
InjectionIntramuscular; Intravenous150 mg/2mL
Injection, powder, for solutionIntramuscular; Intravenous150 mg/1
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous150 mg/4mL
CapsuleRespiratory (inhalation)1662500 IU
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous150 mg/2mL
Powder, for solutionIntramuscular; Intravenous150 mg
Prices
Unit descriptionCostUnit
Coly-mycin m 150 mg vial72.98USD vial
Colistimethate 150 mg vial57.0USD vial
Coly-Mycin S 3.3-3-10 mg/ml Suspension 5ml Bottle49.17USD bottle
Colistimethate For Injection 150 mg/vial35.42USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityAppreciableNot Available
Predicted Properties
PropertyValueSource
Water Solubility4.17 mg/mLALOGPS
logP-1.2ALOGPS
logP-17ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)-4.3ChemAxon
pKa (Strongest Basic)6.46ChemAxon
Physiological Charge-5ChemAxon
Hydrogen Acceptor Count33ChemAxon
Hydrogen Donor Count18ChemAxon
Polar Surface Area706.71 Å2ChemAxon
Rotatable Bond Count44ChemAxon
Refractivity370.19 m3·mol-1ChemAxon
Polarizability161.9 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8904
Blood Brain Barrier-0.8404
Caco-2 permeable-0.6453
P-glycoprotein substrateSubstrate0.7147
P-glycoprotein inhibitor INon-inhibitor0.6292
P-glycoprotein inhibitor IINon-inhibitor0.9498
Renal organic cation transporterNon-inhibitor0.9643
CYP450 2C9 substrateNon-substrate0.8963
CYP450 2D6 substrateNon-substrate0.7999
CYP450 3A4 substrateSubstrate0.5172
CYP450 1A2 substrateNon-inhibitor0.7722
CYP450 2C9 inhibitorNon-inhibitor0.7827
CYP450 2D6 inhibitorNon-inhibitor0.8721
CYP450 2C19 inhibitorNon-inhibitor0.7391
CYP450 3A4 inhibitorNon-inhibitor0.9385
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9888
Ames testNon AMES toxic0.6102
CarcinogenicityNon-carcinogens0.5677
BiodegradationReady biodegradable0.9192
Rat acute toxicity2.6289 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8368
hERG inhibition (predictor II)Non-inhibitor0.6834
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
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as polypeptides. These are peptides containing ten or more amino acid residues.
Kingdom
Organic compounds
Super Class
Organic Polymers
Class
Polypeptides
Sub Class
Not Available
Direct Parent
Polypeptides
Alternative Parents
Cyclic peptides / Macrolactams / N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / N-acyl amines / Organosulfonic acids / Alkanesulfonic acids / Sulfonyls / Secondary alcohols / Lactams
show 8 more
Substituents
Polypeptide / Cyclic alpha peptide / N-acyl-alpha amino acid or derivatives / Macrolactam / Alpha-amino acid amide / N-substituted-alpha-amino acid / Alpha-amino acid or derivatives / N-acyl-amine / Fatty acyl / Fatty amide
show 28 more
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 October 16, 2018 08:34