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. 2022 Sep 28;11(19):5756.
doi: 10.3390/jcm11195756.

Variability of Isavuconazole Trough Concentrations during Longitudinal Therapeutic Drug Monitoring

Léa Bolcato  1 , Anne Thiebaut-Bertrand  2 , Françoise Stanke-Labesque  1   3 , Elodie Gautier-Veyret  1   3
Affiliations

Variability of Isavuconazole Trough Concentrations during Longitudinal Therapeutic Drug Monitoring

Léa Bolcato et al. J Clin Med. .

Abstract

Isavuconazole (ISA), a triazole antifungal agent, is licensed for the treatment of invasive aspergillosis and mucormycosis. Therapeutic drug monitoring (TDM) is a cornerstone of treatment efficacy for triazole antifungals due to their pharmacokinetic variability, except for ISA, for which the utility of TDM is still uncertain. We performed a retrospective study that aimed to assess the inter- and intra-individual variability of ISA trough concentrations (Cmin) and to identify the determinants involved in such variability. ISA Cmin measured in adult patients at the Grenoble Alpes University Hospital between January 2018 and August 2020 were retrospectively analyzed. In total, 304 ISA Cmin for 33 patients were analyzed. The median ISA Cmin was 2.8 [25th−75th percentiles: 2.0−3.7] mg/L. The inter- and intra-individual variability was 41.5% and 30.7%, respectively. Multivariate analysis showed independent covariate effects of dose (β = 0.004 ± 3.56 × 10−4, p < 0.001), Aspartate aminotransférase (ASAT) (β = 0.002 ± 5.41 × 10−4, p = 0.002), and protein levels (β = 0.022 ± 0.004, p < 0.001) on ISA Cmin, whereas C reactive protein levels did not show any association. This study, conducted on a large number of ISA Cmin, shows that ISA exposure exhibits variability, explained in part by the ISA dose, and ASAT and protein levels.

Keywords: isavuconazole; pharmacokinetics; therapeutic drug monitoring; trough concentration.

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Conflict of interest statement

Gautier-Veyret obtained personal fees from Gilead. Gautier-Veyret and Stanke-Labesque report grants from MSD, outside the scope of the work submitted, and grants from Pfizer for this study. Bolcato and Anne Thiebaut-Bertrand have nothing to disclose.

Figures

Figure 1
Figure 1
Flow chart.
Figure 2
Figure 2
Variability of isavuconazole trough concentration (ISA Cmin) values for 33 patients according to the treatment response. Each vertical series of crosses corresponds to repeated ISA Cmin determinations for one patient, with the red cross indicating the median ISA Cmin per patient. Blue lines indicate the proposed therapeutic range at the Grenoble Alpes University Hospital.
Figure 3
Figure 3
Link between isavuconazole trough concentrations (ISA Cmin) and protein level (A), daily dose (B) and ASAT level (C).
See this image and copyright information in PMC

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