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Title: Population pharmacokinetics of colistin methanesulfonate and formed colistin in critically ill patients from a multicenter study provide dosing suggestions for various categories of patients
Authors: S. M. Garonzik
J. Li
V. Thamlikitkul
D. L. Paterson
S. Shoham
J. Jacob
F. P. Silveira
A. Forrest
R. L. Nation
University at Buffalo, State University of New York
Monash University
Mahidol University
University of Queensland, Centre for Clinical Research
Washington Hospital Center
University of Pittsburgh Medical Center
Keywords: Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Jul-2011
Citation: Antimicrobial Agents and Chemotherapy. Vol.55, No.7 (2011), 3284-3294
Abstract: With increasing clinical emergence of multidrug-resistant Gram-negative pathogens and the paucity of new agents to combat these infections, colistin (administered as its inactive prodrug colistin methane-sulfonate [CMS]) has reemerged as a treatment option, especially for critically ill patients. There has been a dearth of pharmacokinetic (PK) data available to guide dosing in critically ill patients, including those on renal replacement therapy. In an ongoing study to develop a population PK model for CMS and colistin, 105 patients have been studied to date; these included 12 patients on hemodialysis and 4 on continuous renal replacement therapy. For patients not on renal replacement, there was a wide variance in creatinine clearance, ranging from 3 to 169 ml/min/1.73 m 2 . Each patient was treated with a physician-selected CMS dosage regimen, and 8 blood samples for PK analysis were collected across a dosage interval on day 3 or 4 of therapy. A linear PK model with two compartments for CMS and one compartment for formed colistin best described the data. Covariates included creatinine clearance on the total clearance of CMS and colistin, as well as body weight on the central volume of CMS. Model-fitted parameter estimates were used to derive suggested loading and maintenance dosing regimens for various categories of patients, including those on hemodialysis and continuous renal replacement. Based on our current understanding of colistin PK and pharmacodynamic relationships, colistin may best be used as part of a highly active combination, especially for patients with moderate to good renal function and/or for organisms with MICs of ≥1.0 mg/liter. Copyright © 2011, American Society for Microbiology. All Rights Reserved.
ISSN: 10986596
Appears in Collections:Scopus 2011-2015

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