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.