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

Mycoses. 2022 Jun;65(6):656-660. doi: 10.1111/myc.13446. Epub 2022 Apr 28.

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.

Publication types

  • Observational Study

MeSH terms

  • Administration, Intravenous
  • Antifungal Agents
  • Critical Illness* / therapy
  • Humans
  • Influenza, Human* / drug therapy
  • Influenza, Human* / prevention & control
  • Triazoles

Substances

  • Antifungal Agents
  • Triazoles
  • posaconazole