Sodium colistimethate
[CAS# 8068-28-8]

Identification

• Classification: Chemical reagent >> Organic reagent >> Sulfonate / sulfinate
• Name: Sodium colistimethate
• Synonyms: Colistinat; Coly-Mycin injectable; Colymycin M; Promixi; Colistin, methyl sulfate, sodium salt
• CAS Registry Number: 8068-28-8
• EC Number: 232-516-9

Safety Data

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Reproductive toxicity	Lact.	-	H362
Reproductive toxicity	Repr.	2	H361

Discovery and Applications

Sodium colistimethate is the sodium salt form of colistimethate, a chemically modified derivative of colistin, which is a polymyxin antibiotic. It is a complex mixture of polymyxin E components that have been chemically sulfonated to improve water solubility and reduce toxicity. The molecular structure of sodium colistimethate consists of a cyclic peptide backbone with a fatty acid tail, characteristic of polymyxins, modified by sulfomethyl groups to form a prodrug suitable for clinical use.

Colistin, the parent compound, was originally isolated from the bacterium *Bacillus polymyxa* in the late 1940s and has potent bactericidal activity against gram-negative bacteria, particularly multidrug-resistant strains such as *Pseudomonas aeruginosa*, *Acinetobacter baumannii*, and *Klebsiella pneumoniae*. However, its clinical use was historically limited due to nephrotoxicity and neurotoxicity.

The development of sodium colistimethate as a prodrug aimed to address these limitations by enhancing water solubility and reducing direct toxicity, enabling safer parenteral and inhalation administration. Once administered, sodium colistimethate is hydrolyzed in vivo to release the active colistin base, which exerts antibacterial effects by interacting with the lipopolysaccharide and phospholipid components of the bacterial outer membrane. This interaction disrupts membrane integrity, leading to increased permeability and bacterial cell death.

Sodium colistimethate is used primarily in the treatment of severe infections caused by multidrug-resistant gram-negative bacteria, especially when other antibiotics are ineffective. It is administered intravenously or via inhalation in cases of respiratory tract infections, including ventilator-associated pneumonia. The prodrug form improves dosing flexibility and reduces irritation at the injection site.

Pharmacokinetically, sodium colistimethate is poorly absorbed orally and requires parenteral routes for systemic effect. The conversion rate to colistin varies among patients, influencing therapeutic levels. Renal function significantly affects clearance, necessitating dose adjustments in patients with impaired kidney function.

Adverse effects associated with sodium colistimethate include nephrotoxicity, neurotoxicity, and hypersensitivity reactions. Monitoring renal function during therapy is essential to minimize toxicity risks.

In summary, sodium colistimethate is a sulfonated prodrug of colistin designed to improve solubility and safety for clinical use against multidrug-resistant gram-negative bacterial infections. Its unique chemical modification enables effective delivery and activation of colistin, preserving its potent antibacterial properties.

References

2007. Enterobacteriaceae Bloodstream Infections: Presence of Integrons, Risk Factors, and Outcome. Antimicrobial Agents and Chemotherapy, 51(7).
DOI: 10.1128/aac.00044-07