Pharmacokinetics and target attainment of intravenous posaconazole in critically ill patients during extracorporeal membrane oxygenation

Ruth Van Daele*, Roger J. Brüggemann, Erwin Dreesen, Pieter Depuydt, Bart Rijnders, Frédéric Cotton, David Fage, Matthias Gijsen, Kenny Van Zwam, Yves Debaveye, Joost Wauters, Isabel Spriet

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)

Abstract

Background: Posaconazole is an antifungal drug used for prophylaxis and treatment of invasive fungal infections. Severe influenza has been identified as a risk factor for invasive pulmonary aspergillosis in critically ill patients. In this population, extracorporeal membrane oxygenation (ECMO) is used as rescue therapy, although little is known about the pharmacokinetics (PK) of posaconazole during ECMO. Objectives: To determine the PK and target attainment of six patients treated with IV posaconazole under ECMO and to develop a population PK model that can be used to simulate the PTA. Methods: Critically ill patients treated with posaconazole and ECMO were included in this study. Plasma samples were collected at several timepoints within one dosing interval on two occasions: an early (Day 2-3) and a late (Day 4-7) sampling day. Daily trough concentrations were measured. Results: The median (IQR) AUC0-24, CL and Vd were 34.3 (28.3-37.7) mg·h/L, 8.7 (8.0-10.6) L/h and 389 (314-740) L, if calculated with non-compartmental analysis based on the observed concentrations. All measured trough concentrations were ≥0.7 mg/L and 11/16 were ≥1 mg/L, which are the haematological thresholds for prophylaxis and treatment of invasive aspergillosis, respectively. The targeted PTA (>90%) was attained for prophylaxis but not for treatment. Conclusions: ECMO does not appear to influence posaconazole exposure compared with haematology patients. However, some trough levels were below the lower limit for treatment. An a priori dose adjustment does not appear to be necessary but drug monitoring is recommended.

Original languageEnglish
Pages (from-to)1234-1241
Number of pages8
JournalJournal of Antimicrobial Chemotherapy
Volume76
Issue number5
Early online date29 Jan 2021
DOIs
Publication statusPublished - 1 May 2021

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