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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/34734
Title: Pharmacokinetics of colistin methanesulfonate and formed colistin in end-Stage renal disease patients receiving continuous ambulatory peritoneal dialysis
Authors: Pornpan Koomanachai
Cornelia B. Landersdorfer
Gong Chen
Hee Ji Lee
Anupop Jitmuang
Somkiat Wasuwattakul
Suchai Sritippayawan
Jian Li
Roger L. Nation
Visanu Thamlikitkul
Mahidol University
Monash University
Monash Institute of Pharmaceutical Sciences
Keywords: Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Jan-2014
Citation: Antimicrobial Agents and Chemotherapy. Vol.58, No.1 (2014), 440-446
Abstract: Colistin, administered intravenously as its inactive prodrug colistin methanesulfonate (CMS), is increasingly used as lastline therapy to combat multidrug-resistant Gram-negative bacteria. CMS dosing needs to be adjusted for renal function. The impact of continuous ambulatory peritoneal dialysis (CAPD) on the pharmacokinetics of both CMS and colistin has not been studied. No CMS dosing recommendations are available for patients receiving CAPD. Eight CAPD patients received a single intravenous CMS dose (150 mg colistin base activity [CBA]) over 30 min. Serial blood and dialysate samples, and cumulative urine where applicable, were collected over 25 h. CMS and colistin concentrations were determined by high-performance liquid chromatography. Population pharmacokinetic modeling and Monte Carlo simulations were conducted. The total body clearance of CMS (excluding CAPD clearance) was 1.77 liters/h (44%) [population mean (betweensubject variability)], while CAPD clearance was 0.088 liter/h (64%). The population mean terminal half-life of CMS was 8.4 h. For colistin, the total clearance/fraction of CMS metabolized to colistin (fm) (excluding CAPD clearance) was 2.74 liters/h (50%), the CAPD clearance was 0.101 liter/h (34%), and the mean terminal half-life was 13.2 h. Monte Carlo simulations suggested a loading dose of 300 mg CBA on day 1 and a maintenance dose of either 150 mg or 200 mg CBA daily to achieve a target average steady-state plasma colistin concentration of 2.5 mg/liter. Clearance by CAPD was low for both CMS and formed colistin. Therefore, CMS doses should not be increased during CAPD. Modeling and simulation enabled us to propose the first evidence-based CMS dosage regimen for CAPD patients. © 2014, American Society for Microbiology.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84891509403&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/34734
ISSN: 10986596
00664804
Appears in Collections:Scopus 2011-2015

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