Exposure to intravenous posaconazole in critically ill patients with influenza: A pharmacokinetic analysis of the POSA-FLU study

Ruth Van Daele; Joost Wauters; Erwin Dreesen; Jerina Boelens; Eric Nulens; Piet Lormans; Lore Vanderbeke; Cato Jacobs; Bart Rijnders; Paul E. Verweij; Roger J. Brüggemann; Isabel Spriet

doi:10.1111/myc.13446

Exposure to intravenous posaconazole in critically ill patients with influenza: A pharmacokinetic analysis of the POSA-FLU study

Ruth Van Daele, Joost Wauters, Erwin Dreesen, Jerina Boelens, Eric Nulens, Piet Lormans, Lore Vanderbeke, Cato Jacobs, Bart Rijnders, Paul E. Verweij, Roger J. Brüggemann, Isabel Spriet

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

Background: Data on posaconazole in the critically ill are scarce. In the POSA-FLU study, we examined the prevention of influenza-associated pulmonary aspergillosis with posaconazole in this population. Methods: In this observational sub-study, we performed a pharmacokinetic analysis, including protein binding and target attainment (TA). Blood samples were collected over a 24 h-dosing interval on both an early (Day 2 or 3) and a later (≥Day 4) treatment day. Results: Target attainment was shown for AUC_0-24 and C_min prophylaxis but not for C_min treatment. Moreover, a saturable protein binding with a significant, positive relationship between albumin concentrations and the maximum binding capacity was observed. Conclusions: Our analysis indicates that posaconazole may be a suitable drug to further investigate for prophylaxis, as TA for prophylaxis was reached. Exposure targets for treatment were insufficiently attained in this population.

Original language	English
Pages (from-to)	656-660
Number of pages	5
Journal	Mycoses
Volume	65
Issue number	6
DOIs	https://doi.org/10.1111/myc.13446
Publication status	Published - Jun 2022
Externally published	Yes

Keywords

critically ill patients
exposure
posaconazole
target attainment
unbound concentrations
Administration, Intravenous
Triazoles
Humans
Influenza, Human/drug therapy
Antifungal Agents
Critical Illness/therapy

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title = "Exposure to intravenous posaconazole in critically ill patients with influenza: A pharmacokinetic analysis of the POSA-FLU study",

abstract = "Background: Data on posaconazole in the critically ill are scarce. In the POSA-FLU study, we examined the prevention of influenza-associated pulmonary aspergillosis with posaconazole in this population. Methods: In this observational sub-study, we performed a pharmacokinetic analysis, including protein binding and target attainment (TA). Blood samples were collected over a 24 h-dosing interval on both an early (Day 2 or 3) and a later (≥Day 4) treatment day. Results: Target attainment was shown for AUC0-24 and Cmin prophylaxis but not for Cmin treatment. Moreover, a saturable protein binding with a significant, positive relationship between albumin concentrations and the maximum binding capacity was observed. Conclusions: Our analysis indicates that posaconazole may be a suitable drug to further investigate for prophylaxis, as TA for prophylaxis was reached. Exposure targets for treatment were insufficiently attained in this population.",

keywords = "critically ill patients, exposure, posaconazole, target attainment, unbound concentrations, Administration, Intravenous, Triazoles, Humans, Influenza, Human/drug therapy, Antifungal Agents, Critical Illness/therapy",

author = "{Van Daele}, Ruth and Joost Wauters and Erwin Dreesen and Jerina Boelens and Eric Nulens and Piet Lormans and Lore Vanderbeke and Cato Jacobs and Bart Rijnders and Verweij, {Paul E.} and Br{\"u}ggemann, {Roger J.} and Isabel Spriet",

note = "{\textcopyright} 2022 Wiley-VCH GmbH.",

year = "2022",

month = jun,

doi = "10.1111/myc.13446",

language = "English",

volume = "65",

pages = "656--660",

journal = "Mycoses",

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TY - JOUR

T1 - Exposure to intravenous posaconazole in critically ill patients with influenza

T2 - A pharmacokinetic analysis of the POSA-FLU study

AU - Van Daele, Ruth

AU - Wauters, Joost

AU - Dreesen, Erwin

AU - Boelens, Jerina

AU - Nulens, Eric

AU - Lormans, Piet

AU - Vanderbeke, Lore

AU - Jacobs, Cato

AU - Rijnders, Bart

AU - Verweij, Paul E.

AU - Brüggemann, Roger J.

AU - Spriet, Isabel

PY - 2022/6

Y1 - 2022/6

N2 - Background: Data on posaconazole in the critically ill are scarce. In the POSA-FLU study, we examined the prevention of influenza-associated pulmonary aspergillosis with posaconazole in this population. Methods: In this observational sub-study, we performed a pharmacokinetic analysis, including protein binding and target attainment (TA). Blood samples were collected over a 24 h-dosing interval on both an early (Day 2 or 3) and a later (≥Day 4) treatment day. Results: Target attainment was shown for AUC0-24 and Cmin prophylaxis but not for Cmin treatment. Moreover, a saturable protein binding with a significant, positive relationship between albumin concentrations and the maximum binding capacity was observed. Conclusions: Our analysis indicates that posaconazole may be a suitable drug to further investigate for prophylaxis, as TA for prophylaxis was reached. Exposure targets for treatment were insufficiently attained in this population.

AB - Background: Data on posaconazole in the critically ill are scarce. In the POSA-FLU study, we examined the prevention of influenza-associated pulmonary aspergillosis with posaconazole in this population. Methods: In this observational sub-study, we performed a pharmacokinetic analysis, including protein binding and target attainment (TA). Blood samples were collected over a 24 h-dosing interval on both an early (Day 2 or 3) and a later (≥Day 4) treatment day. Results: Target attainment was shown for AUC0-24 and Cmin prophylaxis but not for Cmin treatment. Moreover, a saturable protein binding with a significant, positive relationship between albumin concentrations and the maximum binding capacity was observed. Conclusions: Our analysis indicates that posaconazole may be a suitable drug to further investigate for prophylaxis, as TA for prophylaxis was reached. Exposure targets for treatment were insufficiently attained in this population.

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KW - exposure

KW - posaconazole

KW - target attainment

KW - unbound concentrations

KW - Administration, Intravenous

KW - Triazoles

KW - Humans

KW - Influenza, Human/drug therapy

KW - Antifungal Agents

KW - Critical Illness/therapy

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U2 - 10.1111/myc.13446

DO - 10.1111/myc.13446

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AN - SCOPUS:85128879059

SN - 0933-7407

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SP - 656

EP - 660

JO - Mycoses

JF - Mycoses

IS - 6

ER -

Exposure to intravenous posaconazole in critically ill patients with influenza: A pharmacokinetic analysis of the POSA-FLU study

Abstract

Keywords

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