Posaconazole trough concentrations are not influenced by inflammation: a prospective study
van den Heuvel, Edwin R
van der Werf, Tjip S
Span, Lambert F R
Alffenaar, Jan-Willem C
Antifungal Agents/administration & dosage
Triazoles/administration & dosage
International Journal of Antimicrobial Agents, 53(3), 325 - 329. Elsevier
International journal of antimicrobial agents, 53(3), 325 - 329. Elsevier Bedrijfsinformatie b.v.
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BACKGROUND: During inflammation several cytochrome P450 enzymes are down-regulated. Recently it was shown that voriconazole metabolism is reduced during inflammation. Posaconazole, another triazole with broad-spectrum antifungal activity, is only to a limited extent metabolized 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. MATERIALS/METHODS: In a prospective observational study, we enrolled patients (aged ≥18 years) receiving posaconazole prophylaxis or treatment for fungal infections. Samples for posaconazole and C-reactive protein (CRP) concentrations were collected routinely for each patient. A 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. RESULTS: Between August 2015 and June 2017 64 patients were recruited to this study. Data of 54 patients (511 posaconazole samples) were included in the final analysis. The overall median posaconazole concentration was 1.8 mg/L (IQR 1-2.9 mg/L, range 0.1-7.94 mg/L) and the the overall median CRP concentration was 23.5 mg/L (IQR 5-75 mg/L, range 0-457 mg/L). The 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). CONCLUSIONS: Posaconazole concentrations are not influenced by inflammation, reflected by CRP concentration. Therefore, more frequent TDM of posaconazole during inflammation or after an infection subsides is not necessary.