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Colistimethate (Colistimethate Sodium) - Description and Clinical Pharmacology

 
 



FOR INTRAMUSCULAR AND INTRAVENOUS USE

To reduce the development of drug-resistant bacteria and maintain the effectiveness of colistimethate for injection and other antibacterial drugs, colistimethate for injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

DESCRIPTION

Colistimethate for injection (colistimethate sodium) is a sterile parenteral antibiotic product which, when reconstituted (see Reconstitution), is suitable for intramuscular or intravenous administration.

Each vial contains colistimethate sodium or pentasodium colistinmethanesulfonate (equivalent to 150 mg colistin base). Colistimethate sodium appears as a white to slightly yellow lyophilized cake. The sodium content is approximately 0.099 mg (0.0043 mEq) of sodium per milligram of Colistin. Colistimethate sodium is a polypeptide antibiotic with an approximate molecular weight of 1750. The molecular formula is C58 H105 N16 Na5O28 S5 and the structural formula is represented below:

CLINICAL PHARMACOLOGY

Typical serum and urine levels following a single 150 mg dose of colistimethate for injection IM or IV in normal adult subjects are shown in Figure 1.
 

Higher serum levels were obtained at 10 minutes following IV administration. Serum concentration declined with a half-life of 2-3 hours following either intravenous or intramuscular administration in adults and in the pediatric population, including premature infants.

Average urine levels ranged from about 270 mcg/mL at 2 hours to about 15 mcg/mL at 8 hours after intravenous administration and from 200 to about 25 mcg/mL during a similar period following intramuscular administration.

Microbiology:

Colistimethate sodium is a surface active agent which penetrates into and disrupts the bacterial cell membrane. It has been shown to have bactericidal activity against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section:

Aerobic gram-negative microorganisms: Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa.

Susceptibility Tests: Colistimethate sodium is no longer listed as an antimicrobial for routine testing and reporting by clinical microbiology laboratories.

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