Posaconazole trough concentrations are not influenced by inflammation: a prospective study

Anne Grete Märtson, Anette Veringa, Martijn Bakker, Edwin R. van den Heuvel, Daan J. Touw, Tjip S. van der Werf, Lambert F.R. Span, Jan Willem C. Alffenaar (Corresponding author)

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5 Citations (Scopus)
35 Downloads (Pure)

Abstract

During inflammation, several cytochrome P450 enzymes are downregulated. Recently it was shown that voriconazole metabolism is reduced during inflammation. Posaconazole, another triazole with broad-spectrum antifungal activity, is metabolised only to a limited extent by cytochrome P450 enzymes and to a wider extent by phase 2 enzyme systems. The aim of this study was to investigate posaconazole concentrations during inflammation. Patients aged ≥18 years receiving posaconazole prophylaxis or treatment for fungal infections were enrolled in a prospective observational study. Samples for posaconazole and C-reactive protein (CRP) concentrations were collected routinely for each patient. Longitudinal data analysis was performed to analyse the correlation between posaconazole serum trough concentrations and CRP values, corrected for potential factors that could influence the posaconazole concentration. Between August 2015 and June 2017, 64 patients were recruited to this study. Data for 55 patients (511 posaconazole samples) were included in the final analysis. The overall median posaconazole concentration was 1.8 mg/L [interquartile range (IQR) 1–2.9 mg/L, range 0.1–7.94 mg/L] and the overall median CRP concentration was 23.5 mg/L (IQR 5–75 mg/L, range 0–457 mg/L). Longitudinal data analysis showed that only the posaconazole daily dose (in mg/kg body weight) had a significant influence on posaconazole concentration after correction for other factors (P < 0.0001). Posaconazole concentrations were not influenced by CRP concentrations (P = 0.77). Posaconazole concentrations are not influenced by inflammation, reflected by CRP concentration. Therefore, more frequent therapeutic drug monitoring of posaconazole during inflammation or after an infection subsides is not necessary.

Original languageEnglish
Pages (from-to)325-329
Number of pages5
JournalInternational Journal of Antimicrobial Agents
Volume53
Issue number3
DOIs
Publication statusPublished - Mar 2019

Keywords

  • C-reactive protein
  • CRP
  • Haematological malignancy
  • Inflammation
  • Posaconazole
  • Plasma/chemistry
  • Prospective Studies
  • Triazoles/administration & dosage
  • Humans
  • Middle Aged
  • C-Reactive Protein/analysis
  • Male
  • Young Adult
  • Mycoses/drug therapy
  • Adult
  • Female
  • Aged
  • Antifungal Agents/administration & dosage
  • Longitudinal Studies
  • Inflammation/pathology

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