Identification
- Summary
Colistimethate is an antibiotic indicated for treatment of infections caused by susceptible strains of certain gram-negative bacilli. It is particularly useful for targeting sensitive strains of Pseudomonas aeruginosa.
- Brand Names
- Colobreathe, Coly Mycin M, Xylistin
- Generic Name
- Colistimethate
- DrugBank Accession Number
- DB01111
- Background
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.
- Type
- Small Molecule
- Groups
- Approved, Vet approved
- Structure
Structure for Colistimethate (DB01111)
- Weight
- Average: 1634.87
Monoisotopic: 1633.588775306 - Chemical Formula
- C58H105N16O28S5
- Synonyms
- Colistin methanesulfonic acid
- Colistin sulfomethate
- Colistinmethanesulfonic acid
Pharmacology
- Indication
For the treatment of acute or chronic infections due to sensitive strains of certain gram-negative bacilli, particularly Pseudomonas aeruginosa.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Bacterial infection •••••••••••• - Contraindications & Blackbox Warnings
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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.
Target Actions Organism ABacterial outer membrane incorporation into and destabilizationBacteria - 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
- Adverse Effects
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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 Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Colistimethate may decrease the excretion rate of Abacavir which could result in a higher serum level. Aceclofenac The risk or severity of nephrotoxicity can be increased when Colistimethate is combined with Aceclofenac. Acemetacin The risk or severity of nephrotoxicity can be increased when Colistimethate is combined with Acemetacin. Acetaminophen Colistimethate may decrease the excretion rate of Acetaminophen which could result in a higher serum level. Acetylsalicylic acid The risk or severity of nephrotoxicity can be increased when Acetylsalicylic acid is combined with Colistimethate. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Colistimethate sodium XW0E5YS77G 8068-28-8 IQWHCHZFYPIVRV-UHFFFAOYSA-I - Active Moieties
Name Kind UNII CAS InChI Key Colistin prodrug Z67X93HJG1 1066-17-7 YKQOSKADJPQZHB-BRLOSWAASA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Colistimethate for Injection Powder, for solution 150 mg / vial Intramuscular; Intravenous Fresenius Kabi 2014-06-05 Not applicable Canada 
Colistimethate for Injection U.S.P. Powder, for solution 150 mg / vial Intramuscular; Intravenous Sterimax Inc 2002-04-15 Not applicable Canada Colobreathe Capsule 1662500 IU Respiratory (inhalation) Teva B.V. 2016-09-08 Not applicable EU 
Colobreathe Capsule 1662500 IU Respiratory (inhalation) Teva B.V. 2016-09-08 Not applicable EU Colobreathe Capsule 1662500 IU Respiratory (inhalation) Teva B.V. 2016-09-08 Not applicable EU - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Colistimethate Injection 150 mg/2mL Intramuscular; Intravenous Par Pharmaceutical, Inc. 2012-06-01 Not applicable US 
Colistimethate Injection, powder, lyophilized, for solution 150 mg/2mL Intramuscular; Intravenous XGen Pharmaceuticals DJB, Inc. 2011-01-01 Not applicable US Colistimethate Injection, powder, lyophilized, for solution 150 mg/2mL Intramuscular; Intravenous Sagent Pharmaceuticals 2014-12-29 Not applicable US Colistimethate Injection, powder, lyophilized, for solution 150 mg/2mL Intramuscular; Intravenous Paddock Laboratories, Inc. 2014-04-15 2018-06-30 US Colistimethate Injection 150 mg/2mL Intramuscular; Intravenous X-GEN Pharmaceuticals, Inc. 2016-07-01 2020-02-24 US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image COLBIOCIN Colistimethate sodium (180000 IU/ml) + Chloramphenicol (4 MG/ML) + Tetracycline (4.2 MG/ML) Solution / drops Ophthalmic Sifi S.P.A. 2016-01-08 Not applicable Italy 
COLBIOCIN Colistimethate sodium (180000 IU) + Chloramphenicol (10 MG/G) + Tetracycline (5 MG/G) Ointment Ophthalmic Sifi S.P.A. 2014-07-08 Not applicable Italy COLBIOCIN Colistimethate sodium (180000 IU) + Chloramphenicol (4 MG/G) + Tetracycline (4.2 MG/G) Solution / drops Ophthalmic Sifi S.P.A. 2014-07-08 2022-06-01 Italy
Categories
- Drug Categories
- Agents that produce neuromuscular block (indirect)
- Amino Acids, Peptides, and Proteins
- Antimicrobial Cationic Peptides
- Antimicrobial Peptides
- Lipids
- Lipopeptides
- Membrane Proteins
- Nephrotoxic agents
- Peptides
- Peptides, Cyclic
- Polymyxin-class Antibacterial
- Polymyxins
- Pore Forming Cytotoxic Proteins
- Proteins
- Chemical TaxonomyProvided by Classyfire
- 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
- Alcohol / Aliphatic heteromonocyclic compound / Alkanesulfonic acid / Alpha-amino acid amide / Alpha-amino acid or derivatives / Amine / Amino acid or derivatives / Azacycle / Carbonyl group / Carboxamide group show 28 more
- Molecular Framework
- Aliphatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Gram-negative bacilli
Chemical Identifiers
- UNII
- DL2R53P963
- CAS number
- 12705-41-8
- 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
References
- General References
- FDA Approved Drug Products: Coly-Mycin (colistimethate) injection [Link]
- External Links
- Human Metabolome Database
- HMDB0015243
- PubChem Compound
- 70789202
- PubChem Substance
- 46508586
- ChemSpider
- 26329515
- 2708
- ChEBI
- 59662
- Therapeutic Targets Database
- DAP001329
- PharmGKB
- PA164749509
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Colistin
- FDA label
- Download (66.2 KB)
- MSDS
- Download (50.4 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Cystic Fibrosis (CF) 1 3 Completed Prevention Coronavirus Disease 2019 (COVID‑19) / Noncystic Fibrosis Bronchiectasis (NCFB) 1 3 Completed Treatment Bacterial Infections 1 3 Completed Treatment Bloodstream Infections (BSI) / Pneumonia 1 3 Recruiting Treatment Mental Health Issue 1
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
Form Route Strength Ointment Ophthalmic Solution / drops Ophthalmic Solution Intravenous 150.000 mg Powder, for solution Respiratory (inhalation) Powder, for solution Respiratory (inhalation) 1 Mio. I.E. Powder, for solution Respiratory (inhalation) 2 Mio. I.E. Injection Intramuscular; Intravenous Injection, powder, lyophilized, for solution Intramuscular; Intravenous; Respiratory (inhalation) 150 mg Injection Intramuscular; Intravenous 4500.000 iu Injection, powder, for solution Parenteral 1 Mio. I.E. Injection, powder, for solution Parenteral 2 Mio. I.E. Injection, powder, for suspension Intravenous; Respiratory (inhalation) 1 million IU Injection, powder, for solution Intravenous 2 million IU Injection, powder, lyophilized, for solution Intramuscular; Intravenous 150 mg Powder Intravenous; Respiratory (inhalation) 150 mg Injection, powder, for solution Intravenous 160 mg Injection, powder, for solution Intravenous; Respiratory (inhalation) 80 mg Injection, powder, lyophilized, for solution Intravenous; Respiratory (inhalation) 2 million IU Injection, powder, for solution Intravenous 1000.000 IU Injection Intramuscular; Intravenous 150 mg/2mL Injection, powder, for solution Intramuscular; Intravenous 150 mg/1 Injection, powder, lyophilized, for solution Intramuscular; Intravenous 150 mg/1 Injection, powder, lyophilized, for solution Intramuscular; Intravenous 150 mg/4mL Solution Respiratory (inhalation) 80 mg Injection, powder, for solution Parenteral 78.74 mg Solution Parenteral 150.000 mg Capsule Respiratory (inhalation) 1662500 IU Powder Respiratory (inhalation) 1662500 UI Injection, powder, for solution Injection, powder, lyophilized, for solution Intramuscular; Intravenous 150 mg/2mL Powder, for solution Intramuscular; Intravenous 150 mg / vial Powder 160 mg/1vial Solution Parenteral 360.000 mg Injection, powder, lyophilized, for solution Intramuscular; Intravenous; Respiratory (inhalation) Injection, powder, lyophilized, for solution Intramuscular; Intravenous Injection, powder, lyophilized, for solution Intravenous 100000 IU Injection, powder, lyophilized, for solution Intravenous 200000 IU Injection, powder, lyophilized, for solution Intramuscular; Intravenous; Respiratory (inhalation) 4500.000 iu Injection, powder, for solution Intrathecal; Intraventricular 1000000 IU Powder, for solution Respiratory (inhalation) 1000000 IU Injection, powder, for solution 150 mg/1vial Powder 150 mg/1vial - Prices
Unit description Cost Unit Coly-mycin m 150 mg vial 72.98USD vial Colistimethate 150 mg vial 57.0USD vial Coly-Mycin S 3.3-3-10 mg/ml Suspension 5ml Bottle 49.17USD bottle Colistimethate For Injection 150 mg/vial 35.42USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Appreciable Not Available - Predicted Properties
Property Value Source Water Solubility 4.17 mg/mL ALOGPS logP -1.2 ALOGPS logP -17 Chemaxon logS -2.6 ALOGPS pKa (Strongest Acidic) -4.3 Chemaxon pKa (Strongest Basic) 7.06 Chemaxon Physiological Charge -3 Chemaxon Hydrogen Acceptor Count 33 Chemaxon Hydrogen Donor Count 18 Chemaxon Polar Surface Area 706.71 Å2 Chemaxon Rotatable Bond Count 44 Chemaxon Refractivity 370.19 m3·mol-1 Chemaxon Polarizability 161.9 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption - 0.8904 Blood Brain Barrier - 0.8404 Caco-2 permeable - 0.6453 P-glycoprotein substrate Substrate 0.7147 P-glycoprotein inhibitor I Non-inhibitor 0.6292 P-glycoprotein inhibitor II Non-inhibitor 0.9498 Renal organic cation transporter Non-inhibitor 0.9643 CYP450 2C9 substrate Non-substrate 0.8963 CYP450 2D6 substrate Non-substrate 0.7999 CYP450 3A4 substrate Substrate 0.5172 CYP450 1A2 substrate Non-inhibitor 0.7722 CYP450 2C9 inhibitor Non-inhibitor 0.7827 CYP450 2D6 inhibitor Non-inhibitor 0.8721 CYP450 2C19 inhibitor Non-inhibitor 0.7391 CYP450 3A4 inhibitor Non-inhibitor 0.9385 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9888 Ames test Non AMES toxic 0.6102 Carcinogenicity Non-carcinogens 0.5677 Biodegradation Ready biodegradable 0.9192 Rat acute toxicity 2.6289 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8368 hERG inhibition (predictor II) Non-inhibitor 0.6834
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 391.0198 predictedDeepCCS 1.0 (2019) [M+H]+ 392.74353 predictedDeepCCS 1.0 (2019) [M+Na]+ 399.07245 predictedDeepCCS 1.0 (2019)
Targets
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1. Bacterial outer membrane
Yes
Incorporation into and destabilization
References
- 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]
- 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]
- 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 at June 13, 2005 13:24 / Updated at February 20, 2024 23:54