Population pharmacokinetic modeling of multiple-dose intravenous fosfomycin in critically ill patients during continuous venovenous hemodialysis
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Published:2023-10-24
Issue:1
Volume:13
Page:
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ISSN:2045-2322
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Container-title:Scientific Reports
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language:en
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Short-container-title:Sci Rep
Author:
Hüppe TobiasORCID, Götz Katharina M., Meiser Andreas, de Faria Fernandes Andrea, Maurer Felix, Groesdonk Heinrich V., Volk Thomas, Lehr Thorsten, Kreuer Sascha
Abstract
AbstractThe aim of this study was to investigate the pharmacokinetics of multiple-dose intravenous (i.v.) fosfomycin in critically ill patients during continuous venovenous hemodialysis (CVVHD). Non-compartmental analysis and population pharmacokinetic modeling were used to simulate different dosing regimens. We evaluated 15 critically ill patients with renal insufficiency and CVVHD undergoing anti-infective treatment with fosfomycin in our ICU. Five grams of fosfomycin were administered for 120 min every 6 h. Plasma concentrations were determined with and without CVVHD. Pharmacokinetic analysis and simulations were performed using non-linear mixed effects modelling (NONMEM). A two-compartment model with renal and dialysis clearance was most accurate in describing the pharmacokinetics of i.v. fosfomycin during CVVHD. Population parameter estimates were 18.20 L and 20.80 L for the central and peripheral compartment volumes, and 0.26 L/h and 5.08 L/h for renal and intercompartmental clearance, respectively. Urinary creatinine clearance (CLCR) represented a considerable component of renal clearance. Central compartment volume increased over time after the first dose. For patients with CLCR > 50 (90) mL/min and CVVHD, dosage should be increased to ≥ 15 (16) grams of i.v. fosfomycin across three (four) daily doses. Individual CLCR must be considered when dosing i.v. fosfomycin in critically ill patients during CVVHD.
Funder
InfectoPharm, Heppenheim, Germany Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes
Publisher
Springer Science and Business Media LLC
Subject
Multidisciplinary
Reference16 articles.
1. Falagas, M. E., Vouloumanou, E. K., Samonis, G. & Vardakas, K. Z. Fosfomycin. Clin. Microbiol. Rev. 29, 321–347 (2016). 2. Gobernado, M., García, J., Santos, M., Panadero, J. & Diosdado, N. Renal insufficiency and fosfomycin. Chemotherapy. 23, 200–203 (1977). 3. Bouchet, J. L. et al. Pharmacokinetics of intravenous and intraperitoneal fosfomycin in continuous ambulatory peritoneal dialysis. Clin. Nephrol. 29, 35–40 (1988). 4. Fernandez Lastra, C., Mariño, E. L., Dominguez-Gil, A., Tabernero, J. M. & Grande Villoria, J. Pharmacokinetics of phosphomycin during haemofiltration. Br. J. Clin. Pharmacol. 117, 477–480 (1984). 5. Parker, S., Lipman, J., Koulenti, D., Dimopoulos, G. & Roberts, J. A. What is the relevance of fosfomycin pharmacokinetics in the treatment of serious infections in critically ill patients? A systematic review. Int. J. Antimicrob. Agents. 42, 289–293 (2013).
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1. Research Progress in Pharmacokinetics;Journal of Advances in Physical Chemistry;2024
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