Pharmacokinetic variability and target attainment of fluconazole in critically ill patients

[en] Background: Fluconazole is one of the oldest antifungal drugs. Previous studies have raised concerns considering variability in exposure and inadequate target attainment in critically ill pa-tients. The current study aims to define variability and target attainment for fluconazole exposure in a large group of critically ill patients. Methods: In this pharmacokinetic study, daily plasma trough samples and, if possible, 24 h urine samples were collected to determine fluconazole concentration. A minimum target trough concentration of 10–15 mg/L was selected, corresponding to a free area under the concentration–time curve above the minimum inhibitory concentration (fAUC/MIC) of at least 100 for an MIC of 4 mg/L. Covariates that significantly influenced fluconazole exposure were identified. Results: In total, 288 plasma samples from 43 patients, with a median age of 66 years, were included. The median fluconazole trough concentration was 22.9 mg/L. A notable component of the measured concentrations was below the target trough concentrations (13% <10 mg/L and 27% <15 mg/L). The intra-and intersubject variability were 28.3% and 50.5%, respectively. The main covariates determining fluconazole exposure were the administered dose (mg/kg), augmented renal clearance, and renal replacement therapy. Conclusions: Fluconazole trough concentrations are variable in critically ill patients and a considerable number of these concentrations was below the pre-defined target trough concentrations. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Disciplines :

Laboratory medicine & medical technology

Author, co-author :

Van Daele, R.; Clinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, 3000, Belgium, Pharmacy Department, University Hospitals Leuven, Leuven, 3000, Belgium

Wauters, J.; Laboratory for Clinical Infectious and Inflammatory Disorders, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, 3000, Belgium, Medical Intensive Care Unit, University Hospitals Leuven, Leuven, 3000, Belgium

Lagrou, K.; Clinical Department of Laboratory Medicine and National Reference Centre for Mycosis, Excellence Centre for Medical Mycology (ECMM), University Hospitals Leuven, Leuven, 3000, Belgium, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, 3000, Belgium

Denooz, Raphael ; Centre Hospitalier Universitaire de Liège - CHU > > Service de toxicologie clinique, médicolégale, environnementale et en entreprise

Hayette, Marie-Pierre ; Centre Hospitalier Universitaire de Liège - CHU > > Service de microbiologie clinique

Gijsen, M.; Clinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, 3000, Belgium, Pharmacy Department, University Hospitals Leuven, Leuven, 3000, Belgium

Brüggemann, R.J.; Department of Pharmacy and Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, 6525 GA, Netherlands, Center of Expertise in Mycology Radboudumc/CWZ, Radboud University Medical Center, Nijmegen, 6525 GA, Netherlands

Debaveye, Y.; Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, 3000, Belgium, Intensive Care Unit, University Hospitals Leuven, Leuven, 3000, Belgium

Spriet, I.; Clinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, 3000, Belgium, Pharmacy Department, University Hospitals Leuven, Leuven, 3000, Belgium

Language :

English

Title :

Pharmacokinetic variability and target attainment of fluconazole in critically ill patients

Publication date :

2021

Journal title :

Microorganisms

eISSN :

2076-2607

Publisher :

MDPI

Volume :

Issue :

Peer reviewed :

Peer Reviewed verified by ORBi

Funding text :

Conflicts of Interest: J.W. reports grants from M.S.D. during the conduct of the study. J.W. received speaker fees, travel grants, and investigator-initiated grants from M.S.D., Gilead, and Pfizer, outside of the submitted work. K.L. received consultancy fees from SMB Laboratoires Brussels and Gilead, travel support from Pfizer, speaker fees from FUJIFILM WAKO and Pfizer, and a grant from Thermo Fisher Scientific. M.-P.H. received travel support and speaker fees from Pfizer, travel support from Gilead, and M.S.D. R.B. reports and is consultant to F2G, Mundipharma, and Amplyx and has received unrestricted grants in the past five years from Gilead, Pfizer, M.S.D., and Astellas. He has provided lectures for Gilead and Pfizer. All contracts were with Radboudumc and all invoices were paid to Radboudumc. I.S. is supported by the Clinical Research Fund of UZ Leuven and served as a consultant to, and has received unrestricted travel and research grants from, Gilead Sciences, Merck Sharpe and Dohme Corp., Pfizer Inc., and Cidara. All contracts were through and invoiced by UZ and KU Leuven. R.V.D., R.D., M.G., and Y.D. have nothing to disclose.

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since 21 October 2022

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