Renal Disposition of Colistin in the Isolated Perfused Rat Kidney
Date
2009
Authors
Ma, Z.
Wang, J.
Nation, R.
Li, J.
Turnidge, J.
Coulthard, K.
Milne, R.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Antimicrobial Agents and Chemotherapy, 2009; 53(7):2857-2864
Statement of Responsibility
Zheng Ma, Jiping Wang, Roger L. Nation, Jian Li, John D. Turnidge, Kingsley Coulthard, and Robert W. Milne
Conference Name
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 µg/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 (CLR) 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 CLR/(fu x GFR), where fu 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 µM), Gly-Gly (833 µM), and HCl (2,500, 5,000, and 10,000 µM). 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.
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Dissertation Note
Provenance
Description
Link to a related website: http://europepmc.org/articles/pmc2704651?pdf=render, Open Access via Unpaywall
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Rights
Copyright 2009 American Society for Microbiology