Contribution of voriconazole N-oxide plasma concentration measurements to voriconazole therapeutic drug monitoring in patients with invasive fungal infection.
antifungal
invasive fungal infection
metabolic ratio
therapeutic drug monitoring
voriconazole
voriconazole N-oxide
Journal
Mycoses
ISSN: 1439-0507
Titre abrégé: Mycoses
Pays: Germany
ID NLM: 8805008
Informations de publication
Date de publication:
May 2023
May 2023
Historique:
revised:
18
01
2023
received:
04
10
2022
accepted:
21
01
2023
medline:
4
4
2023
pubmed:
27
1
2023
entrez:
26
1
2023
Statut:
ppublish
Résumé
Voriconazole (VRC), a widely used triazole antifungal, exhibits significant inter- and intra-individual pharmacokinetic variability. The main metabolite voriconazole N-oxide (NOX) can provide information on the patient's drug metabolism capacity. Our objectives were to implement routine measurement of NOX concentrations and to describe the metabolic ratio (MR), and the contribution of the MR to VRC therapeutic drug monitoring (TDM) by proposing a suggested dosage-adjustment algorithm. Sixty-one patients treated with VRC were prospectively included in the study, and VRC and NOX levels were assayed by LC-MS/MS. A mixed logistic model on repeated measures was implemented to analyse risk factors for the patient's concentration to be outside the therapeutic range. Based on 225 measurements, the median and interquartile range were 2.4 μg/ml (1.2; 4.2), 2.1 μg/ml (1.5; 3.0) and 1.0 (0.6; 1.9) for VRC, NOX and the MR, respectively. VRC C Measurement of NOX resulted useful for TDM of patients treated with VRC. The MR using NOX informed interpretation and clinical decision-making and is very interesting for complex patients. VRC phenotyping based on the MR is now performed routinely in our institution. A dosing algorithm has been suggested from these results.
Sections du résumé
BACKGROUND
BACKGROUND
Voriconazole (VRC), a widely used triazole antifungal, exhibits significant inter- and intra-individual pharmacokinetic variability. The main metabolite voriconazole N-oxide (NOX) can provide information on the patient's drug metabolism capacity.
OBJECTIVES
OBJECTIVE
Our objectives were to implement routine measurement of NOX concentrations and to describe the metabolic ratio (MR), and the contribution of the MR to VRC therapeutic drug monitoring (TDM) by proposing a suggested dosage-adjustment algorithm.
PATIENTS AND METHODS
METHODS
Sixty-one patients treated with VRC were prospectively included in the study, and VRC and NOX levels were assayed by LC-MS/MS. A mixed logistic model on repeated measures was implemented to analyse risk factors for the patient's concentration to be outside the therapeutic range.
RESULTS
RESULTS
Based on 225 measurements, the median and interquartile range were 2.4 μg/ml (1.2; 4.2), 2.1 μg/ml (1.5; 3.0) and 1.0 (0.6; 1.9) for VRC, NOX and the MR, respectively. VRC C
CONCLUSIONS
CONCLUSIONS
Measurement of NOX resulted useful for TDM of patients treated with VRC. The MR using NOX informed interpretation and clinical decision-making and is very interesting for complex patients. VRC phenotyping based on the MR is now performed routinely in our institution. A dosing algorithm has been suggested from these results.
Substances chimiques
Voriconazole
JFU09I87TR
Antifungal Agents
0
Oxides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
396-404Informations de copyright
© 2023 The Authors. Mycoses published by Wiley-VCH GmbH.
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