JAC Advance Access originally published online on March 24, 2004
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Journal of Antimicrobial Chemotherapy (2004) 53, 837-840
© 2004 The British Society for Antimicrobial Chemotherapy
Pharmacokinetics of colistin methanesulphonate and colistin in rats following an intravenous dose of colistin methanesulphonate
1 Centre for Pharmaceutical Research and 4 School of Pharmaceutical, Molecular and Biomedical Sciences, University of South Australia, Adelaide; 2 Facility for Anti-infective Drug Development and Innovation, Victorian College of Pharmacy, Monash University, Parkville, Melbourne, Vic 3052; 3 Department of Microbiology and Infectious Diseases and 5 Department of Pharmacy, Women’s and Children’s Hospital, North Adelaide, Australia
Received 7 May 2003, returned 21 July 2003; revised 3 February 2004; accepted 5 February 2004
Objectives: To determine the disposition of colistin methanesulphonate (CMS) and colistin following intravenous (iv) administration of CMS in rats.
Methods: Five rats received a single iv bolus of 15 mg/kg CMS. Plasma concentrations of CMS and of colistin formed by the hydrolysis of CMS were determined by HPLC. The pharmacokinetic parameters of CMS and colistin were calculated using non-compartmental analysis.
Results: Total body clearance, volume of distribution at steady state and terminal half-life of CMS averaged 11.7 mL/min/kg, 299 mL/kg and 23.6 min, respectively. The mean terminal half-life of colistin was 55.7 min. Approximately 60% of the dose was eliminated via the urine in 24 h and presented as a mixture of CMS and colistin.
Conclusions: Colistin appeared in plasma soon after administration of CMS, indicating rapid conversion of CMS into colistin. CMS had a shorter terminal half-life than did colistin, indicating that the disposition of the colistin generated from CMS was rate-limited by its elimination. Most of the dose was recovered in urine, half in the form of colistin. The high percentage of colistin recovered in urine was believed to be formed by hydrolysis of CMS in the bladder and in the collection vessel, and/or conversion from CMS in the kidney.
Keywords: antibacterials, HPLC, Pseudomonas aeruginosa
* Corresponding author. Tel: +61-3-9903-9061; Fax: +61-3-9903-9629; E-mail: Roger.Nation{at}vcp.monash.edu.au
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