Pharmacokinetic Variability and Target Attainment of Fluconazole in Critically Ill Patients
<i>Background</i>: 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...
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MDPI AG
2021-09-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/9/10/2068 |
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| author | Ruth Van Daele Joost Wauters Katrien Lagrou Raphaël Denooz Marie-Pierre Hayette Matthias Gijsen Roger J. Brüggemann Yves Debaveye Isabel Spriet |
| author_facet | Ruth Van Daele Joost Wauters Katrien Lagrou Raphaël Denooz Marie-Pierre Hayette Matthias Gijsen Roger J. Brüggemann Yves Debaveye Isabel Spriet |
| author_sort | Ruth Van Daele |
| collection | DOAJ |
| description | <i>Background</i>: 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. <i>Methods</i>: 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 (<i>f</i>AUC/MIC) of at least 100 for an MIC of 4 mg/L. Covariates that significantly influenced fluconazole exposure were identified. <i>Results</i>: 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. <i>Conclusions</i>: Fluconazole trough concentrations are variable in critically ill patients and a considerable number of these concentrations was below the predefined target trough concentrations. |
| first_indexed | 2024-03-10T06:21:59Z |
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| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T06:21:59Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-555544e255df4869b0a45eb0144d87352023-11-22T19:13:44ZengMDPI AGMicroorganisms2076-26072021-09-01910206810.3390/microorganisms9102068Pharmacokinetic Variability and Target Attainment of Fluconazole in Critically Ill PatientsRuth Van Daele0Joost Wauters1Katrien Lagrou2Raphaël Denooz3Marie-Pierre Hayette4Matthias Gijsen5Roger J. Brüggemann6Yves Debaveye7Isabel Spriet8Clinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, BelgiumLaboratory for Clinical Infectious and Inflammatory Disorders, Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, BelgiumClinical Department of Laboratory Medicine and National Reference Centre for Mycosis, Excellence Centre for Medical Mycology (ECMM), University Hospitals Leuven, 3000 Leuven, BelgiumLaboratory of Clinical, Forensic, Environmental and Industrial Toxicology, CHU Sart-Tilman, University of Liège, 4000 Liège, BelgiumLaboratory of Clinical Microbiology, Centre for Interdisciplinary Research on Medicines (CIRM), University of Liège, 4000 Liège, BelgiumClinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, BelgiumDepartment of Pharmacy and Radboud Institute for Health Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsLaboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, BelgiumClinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium<i>Background</i>: 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. <i>Methods</i>: 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 (<i>f</i>AUC/MIC) of at least 100 for an MIC of 4 mg/L. Covariates that significantly influenced fluconazole exposure were identified. <i>Results</i>: 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. <i>Conclusions</i>: Fluconazole trough concentrations are variable in critically ill patients and a considerable number of these concentrations was below the predefined target trough concentrations.https://www.mdpi.com/2076-2607/9/10/2068fluconazolecritically ill patientspharmacokineticstarget attainmentvariabilityexposure |
| spellingShingle | Ruth Van Daele Joost Wauters Katrien Lagrou Raphaël Denooz Marie-Pierre Hayette Matthias Gijsen Roger J. Brüggemann Yves Debaveye Isabel Spriet Pharmacokinetic Variability and Target Attainment of Fluconazole in Critically Ill Patients Microorganisms fluconazole critically ill patients pharmacokinetics target attainment variability exposure |
| 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 | fluconazole critically ill patients pharmacokinetics target attainment variability exposure |
| url | https://www.mdpi.com/2076-2607/9/10/2068 |
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