JAC Advance Access published online on March 24, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh167
© 2004 by The British Society for Antimicrobial Chemotherapy
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Original article
1 Centre for Pharmaceutical
Research, University of South Australia,
Adelaide; Facility for Anti-infective
Drug Development and Innovation, Victorian College of Pharmacy,
Monash University, Parkville, Melbourne, Vic 3052;
* Corresponding author. E-mail: Roger.Nation{at}vcp.monash.edu.au.
Received 7 May 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
Pharmacokinetics of colistin methanesulphonate
and colistin in rats following an intravenous dose of colistin methanesulphonate
2 Centre for Pharmaceutical
Research, University of South Australia,
Adelaide
3 Facility for Anti-infective
Drug Development and Innovation, Victorian College of Pharmacy,
Monash University, Parkville, Melbourne, Vic 3052;
4 Department of Microbiology and Infectious
Diseases, Women’s and Children’s Hospital,
North Adelaide, Australia
5 School of Pharmaceutical,
Molecular and Biomedical Sciences, University of South Australia,
Adelaide;
6 Department
of Pharmacy, Women’s and Children’s Hospital,
North Adelaide, Australia
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  F. E. A. Ali, G. Cao, A. Poudyal, T. Vaara, R. L. Nation, M. Vaara, and J. Li Pharmacokinetics of novel antimicrobial cationic peptides NAB 7061 and NAB 739 in rats following intravenous administration J. Antimicrob. Chemother., November 1, 2009; 64(5): 1067 - 1070. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Plachouras, M. Karvanen, L. E. Friberg, E. Papadomichelakis, A. Antoniadou, I. Tsangaris, I. Karaiskos, G. Poulakou, F. Kontopidou, A. Armaganidis, et al. Population Pharmacokinetic Analysis of Colistin Methanesulfonate and Colistin after Intravenous Administration in Critically Ill Patients with Infections Caused by Gram-Negative Bacteria Antimicrob. Agents Chemother., August 1, 2009; 53(8): 3430 - 3436. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Wallace, J. Li, Craig. R. Rayner, K. Coulthard, and R. L. Nation Stability of Colistin Methanesulfonate in Pharmaceutical Products and Solutions for Administration to Patients Antimicrob. Agents Chemother., September 1, 2008; 52(9): 3047 - 3051. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Bergen, J. Li, R. L. Nation, J. D. Turnidge, K. Coulthard, and R. W. Milne Comparison of once-, twice- and thrice-daily dosing of colistin on antibacterial effect and emergence of resistance: studies with Pseudomonas aeruginosa in an in vitro pharmacodynamic model J. Antimicrob. Chemother., March 1, 2008; 61(3): 636 - 642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Wallace, J. Li, R. L. Nation, C. R. Rayner, D. Taylor, D. Middleton, R. W. Milne, K. Coulthard, and J. D. Turnidge Subacute Toxicity of Colistin Methanesulfonate in Rats: Comparison of Various Intravenous Dosage Regimens Antimicrob. Agents Chemother., March 1, 2008; 52(3): 1159 - 1161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Li, C. R. Rayner, R. L. Nation, R. J. Owen, D. Spelman, K. E. Tan, and L. Liolios Heteroresistance to Colistin in Multidrug-Resistant Acinetobacter baumannii. Antimicrob. Agents Chemother., September 1, 2006; 50(9): 2946 - 2950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Li and R. L. Nation Comment on: Pharmacokinetics of inhaled colistin in patients with cystic fibrosis J. Antimicrob. Chemother., July 1, 2006; 58(1): 222 - 223. [Full Text] [PDF]
|
|
|
|
|
|
P. J. Bergen, J. Li, C. R. Rayner, and R. L. Nation Colistin Methanesulfonate Is an Inactive Prodrug of Colistin against Pseudomonas aeruginosa. Antimicrob. Agents Chemother., June 1, 2006; 50(6): 1953 - 1958. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Li, C. R. Rayner, R. L. Nation, R. Deans, R. Boots, N. Widdecombe, A. Douglas, and J. Lipman Pharmacokinetics of Colistin Methanesulfonate and Colistin in a Critically Ill Patient Receiving Continuous Venovenous Hemodiafiltration Antimicrob. Agents Chemother., November 1, 2005; 49(11): 4814 - 4815. [Full Text] [PDF]
|
|