Please use this identifier to cite or link to this item:
Scopus Web of ScienceĀ® Altmetric
Type: Journal article
Title: Renal Disposition of Colistin in the Isolated Perfused Rat Kidney
Author: Ma, Z.
Wang, J.
Nation, R.
Li, J.
Turnidge, J.
Coulthard, K.
Milne, R.
Citation: Antimicrobial Agents and Chemotherapy, 2009; 53(7):2857-2864
Publisher: Amer Soc Microbiology
Issue Date: 2009
ISSN: 0066-4804
Statement of
Zheng Ma, Jiping Wang, Roger L. Nation, Jian Li, John D. Turnidge, Kingsley Coulthard, and Robert W. Milne
Abstract: Nephrotoxicity is an important limitation to the clinical use of colistin against Pseudomonas aeruginosa and other gram-negative pathogens. Previous work reported net tubular reabsorption of colistin by the kidney in vivo, but there is no knowledge of its disposition within the kidney. This study investigated the renal disposition and potential transport mechanisms of colistin in the isolated perfused rat kidney (IPK) model by perfusing with colistin sulfate alone (2 microg/ml) or in the presence of potential inhibitors (tetraethylammonium [TEA], glycine-glycine [Gly-Gly], or hydrochloric acid [HCl]) at three different concentrations. When perfused alone, the renal clearances (CL(R)) for colistin A and B (the major components of colistin) in control kidneys were constant and low (mean values < 0.05 ml/min throughout the perfusion). The mean clearance ratios [CR, defined as CL(R)/(f(u) x GFR), where f(u) is the fraction of drug unbound in perfusate and GFR is the glomerular filtration rate] were significantly less than 1. It was concluded that there is net tubular reabsorption of colistin, and this exceeded the reabsorption of water. Less than 10% eliminated from perfusate was recovered in urine, suggesting considerable renal accumulation of colistin. The CR values for colistin were significantly increased when perfused with TEA (500 microM), Gly-Gly (833 microM), and HCl (2,500, 5,000, and 10,000 microM). It is proposed that renal reabsorption of colistin may involve organic cation transporters (inhibited by TEA) and peptide transporters (inhibited by Gly-Gly) and that the process is sensitive to the pH of urine.
Keywords: Kidney
Rats, Sprague-Dawley
Anti-Bacterial Agents
Glomerular Filtration Rate
In Vitro Techniques
DOI: 10.1128/AAC.00030-09
Published version:
Appears in Collections:Aurora harvest 5
Molecular and Biomedical Science publications

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.