Population pharmacokinetics of fosfomycin in critically ill patients

Parker, Suzanne L., Frantzeskaki, Frantzeska, Wallis, Steven C., Diakaki, Chryssa, Giamarellou, Helen, Koulenti, Despoina, Karaiskos, Ilias, Lipman, Jeffrey, Dimopoulos, George and Roberts, Jason A. (2015) Population pharmacokinetics of fosfomycin in critically ill patients. Antimicrobial Agents and Chemotherapy, 59 10: 6471-6476. doi:10.1128/AAC.01321-15

Author Parker, Suzanne L.
Frantzeskaki, Frantzeska
Wallis, Steven C.
Diakaki, Chryssa
Giamarellou, Helen
Koulenti, Despoina
Karaiskos, Ilias
Lipman, Jeffrey
Dimopoulos, George
Roberts, Jason A.
Title Population pharmacokinetics of fosfomycin in critically ill patients
Journal name Antimicrobial Agents and Chemotherapy   Check publisher's open access policy
ISSN 1098-6596
Publication date 2015-10-01
Year available 2015
Sub-type Article (original research)
DOI 10.1128/AAC.01321-15
Open Access Status File (Publisher version)
Volume 59
Issue 10
Start page 6471
End page 6476
Total pages 6
Place of publication Washington, United States
Publisher American Society for Microbiology
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
School of Pharmacy Publications
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