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

7 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

Access to Document

10.1111/myc.13446

Cite this

@article{f7cb004e8d55434c9de4c529de8d3909,

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",

issn = "0933-7407",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "6",

}

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.

KW - critically ill patients

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

UR - https://www.scopus.com/pages/publications/85128879059

U2 - 10.1111/myc.13446

DO - 10.1111/myc.13446

M3 - Article

C2 - 35437848

AN - SCOPUS:85128879059

SN - 0933-7407

VL - 65

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

Access to Document

Fingerprint

Cite this