title: Colistin methanesulfonate and colistin pharmacokinetics in critically ill patients receiving continuous venovenous hemodiafiltration.
abstract: This report describes the pharmacokinetics of colistin methanesulfonate (CMS) and colistin in five intensive care unit patients receiving continuous venovenous hemodiafiltration. For CMS, the mean maximum concentration of drug in plasma (C(max)) after the fourth dose was 6.92 mg/liter and total clearance (CL) 8.23 liters/h. For colistin, the mean concentration was 0.92 mg/liter and CL/metabolized fraction (f(m)) 18.91 liters/h. Colistin concentrations were below the current MIC breakpoints, and the area under the concentration-time curve for the free, unbound fraction of the drug over 24 h in the steady state divided by the MIC (fAUC/MIC) was lower than recommended, suggesting that a dosage regimen of 160 mg CMS every 8 h (q8h) is inadequate.
authors.affiliation: Department of Medical Sciences, Section for Infectious Diseases, Uppsala University, Uppsala, Sweden. matti.karvanen@medsci.uu.se
authors.forename: Matti
authors.initials: M
authors.lastname: Karvanen
authors.forename: Diamantis
authors.initials: D
authors.lastname: Plachouras
authors.forename: Lena E
authors.initials: LE
authors.lastname: Friberg
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Paramythiotou
authors.forename: Evangelos
authors.initials: E
authors.lastname: Papadomichelakis
authors.forename: Ilias
authors.initials: I
authors.lastname: Karaiskos
authors.forename: Iraklis
authors.initials: I
authors.lastname: Tsangaris
authors.forename: Apostolos
authors.initials: A
authors.lastname: Armaganidis
authors.forename: Otto
authors.initials: O
authors.lastname: Cars
authors.forename: Helen
authors.initials: H
authors.lastname: Giamarellou
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003091:Colistin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D016638:Critical Illness / Q000628:therapy; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D005260:Female; D017583:Hemodiafiltration; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged
chemical_list: D000900:Anti-Bacterial Agents; C004691:colistinmethanesulfonic acid; D003091:Colistin