title: Population Pharmacokinetics of Fosfomycin in Critically Ill Patients.
abstract: This study describes the population pharmacokinetics of fosfomycin in critically ill patients. In this observational study, serial blood samples were taken over several dosing intervals of intravenous fosfomycin treatment. Blood samples were analyzed using a validated liquid chromatography-tandem mass spectrometry technique. A population pharmacokinetic analysis was performed using nonlinear mixed-effects modeling. Five hundred fifteen blood samples were collected over one to six dosing intervals from 12 patients. The mean (standard deviation) age was 62 (17) years, 67% of patients were male, and creatinine clearance (CLCR) ranged from 30 to 300 ml/min. A two-compartment model with between-subject variability on clearance and volume of distribution of the central compartment (Vc) described the data adequately. Calculated CLCR was supported as a covariate on fosfomycin clearance. The mean parameter estimates for clearance on the first day were 2.06 liters/h, Vc of 27.2 liters, intercompartmental clearance of 19.8 liters/h, and volume of the peripheral compartment of 22.3 liters. We found significant pharmacokinetic variability for fosfomycin in this heterogeneous patient sample, which may be explained somewhat by the observed variations in renal function.
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Parker
authors.affiliation: Critical Care Department, Attikon University Hospital, Athens, Greece Medical School, University of Athens, Athens, Greece.
authors.forename: Frantzeska
authors.initials: F
authors.lastname: Frantzeskaki
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Wallis
authors.affiliation: Critical Care Department, Attikon University Hospital, Athens, Greece Medical School, University of Athens, Athens, Greece.
authors.forename: Chryssa
authors.initials: C
authors.lastname: Diakaki
authors.affiliation: 6th Department of Internal Medicine, Hygeia General Hospital, Athens, Greece.
authors.forename: Helen
authors.initials: H
authors.lastname: Giamarellou
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia Critical Care Department, Attikon University Hospital, Athens, Greece.
authors.forename: Despoina
authors.initials: D
authors.lastname: Koulenti
authors.affiliation: 6th Department of Internal Medicine, Hygeia General Hospital, Athens, Greece.
authors.forename: Ilias
authors.initials: I
authors.lastname: Karaiskos
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia Royal Brisbane and Women's Hospital, Brisbane, Australia.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
authors.affiliation: Critical Care Department, Attikon University Hospital, Athens, Greece Medical School, University of Athens, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Dimopoulos
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia Royal Brisbane and Women's Hospital, Brisbane, Australia j.roberts2@uq.edu.au.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
mesh_terms: D018806:APACHE; D000368:Aged; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D016638:Critical Illness; D004334:Drug Administration Schedule; D005260:Female; D005578:Fosfomycin / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D016905:Gram-Negative Bacterial Infections / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D016908:Gram-Positive Bacterial Infections / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D006115:Greece; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009102:Multiple Organ Failure / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D009894:Opportunistic Infections / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D005578:Fosfomycin