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Pharmacokinetic Variability and Target Attainment of Fluconazole in Critically Ill Patients

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 patients. The current study aims to define variability and target attainment for fluconazole exposure in a large...

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Autores principales: Van Daele, Ruth, Wauters, Joost, Lagrou, Katrien, Denooz, Raphaël, Hayette, Marie-Pierre, Gijsen, Matthias, Brüggemann, Roger J., Debaveye, Yves, Spriet, Isabel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538061/
https://www.ncbi.nlm.nih.gov/pubmed/34683388
http://dx.doi.org/10.3390/microorganisms9102068
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author Van Daele, Ruth
Wauters, Joost
Lagrou, Katrien
Denooz, Raphaël
Hayette, Marie-Pierre
Gijsen, Matthias
Brüggemann, Roger J.
Debaveye, Yves
Spriet, Isabel
author_facet Van Daele, Ruth
Wauters, Joost
Lagrou, Katrien
Denooz, Raphaël
Hayette, Marie-Pierre
Gijsen, Matthias
Brüggemann, Roger J.
Debaveye, Yves
Spriet, Isabel
author_sort Van Daele, Ruth
collection PubMed
description 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 patients. 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 predefined target trough concentrations.
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spelling pubmed-85380612021-10-24 Pharmacokinetic Variability and Target Attainment of Fluconazole in Critically Ill Patients Van Daele, Ruth Wauters, Joost Lagrou, Katrien Denooz, Raphaël Hayette, Marie-Pierre Gijsen, Matthias Brüggemann, Roger J. Debaveye, Yves Spriet, Isabel Microorganisms Article 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 patients. 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 predefined target trough concentrations. MDPI 2021-09-30 /pmc/articles/PMC8538061/ /pubmed/34683388 http://dx.doi.org/10.3390/microorganisms9102068 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Van Daele, Ruth
Wauters, Joost
Lagrou, Katrien
Denooz, Raphaël
Hayette, Marie-Pierre
Gijsen, Matthias
Brüggemann, Roger J.
Debaveye, Yves
Spriet, Isabel
Pharmacokinetic Variability and Target Attainment of Fluconazole in Critically Ill Patients
title Pharmacokinetic Variability and Target Attainment of Fluconazole in Critically Ill Patients
title_full Pharmacokinetic Variability and Target Attainment of Fluconazole in Critically Ill Patients
title_fullStr Pharmacokinetic Variability and Target Attainment of Fluconazole in Critically Ill Patients
title_full_unstemmed Pharmacokinetic Variability and Target Attainment of Fluconazole in Critically Ill Patients
title_short Pharmacokinetic Variability and Target Attainment of Fluconazole in Critically Ill Patients
title_sort pharmacokinetic variability and target attainment of fluconazole in critically ill patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538061/
https://www.ncbi.nlm.nih.gov/pubmed/34683388
http://dx.doi.org/10.3390/microorganisms9102068
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