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Inflammation is associated with voriconazole trough concentrations
Marjolijn J P van Wanrooy1, Lambert F R Span2, Michael G G Rodgers3
1University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.
Antimicrobial Agents and Chemotherapy
|September 17, 2014
Summary
Inflammation significantly impacts voriconazole levels. Higher C-reactive protein (CRP) concentrations correlate with increased voriconazole trough concentrations, suggesting inflammation influences drug levels.
Area of Science:
- Pharmacology
- Clinical Pharmacy
- Infectious Diseases
Background:
- Voriconazole exhibits significant inter-individual concentration variability, not fully explained by known factors.
- Inflammatory stimuli can alter cytochrome P450 isoenzyme activity and expression, potentially affecting drug metabolism.
- Understanding factors influencing voriconazole levels is crucial for optimizing therapeutic drug monitoring.
Purpose of the Study:
- To investigate the correlation between inflammation, indicated by C-reactive protein (CRP) levels, and voriconazole trough concentrations.
- To determine if CRP is a significant predictor of voriconazole variability in patients.
Main Methods:
- Retrospective chart review of 128 patients with concurrent steady-state voriconazole trough and CRP concentrations.
- Patients categorized into groups based on inflammation severity (severe, moderate, no/mild).
- Linear regression analysis performed, adjusting for covariates like age, gender, dose, and co-medications.
Main Results:
- Significantly higher voriconazole trough concentrations observed in patients with severe inflammation compared to moderate or mild inflammation.
- Voriconazole doses (mg/kg) were similar across all inflammation groups.
- A significant positive association found between CRP concentration and voriconazole trough concentration (P < 0.001); each 1 mg/L increase in CRP correlated with a 0.015 mg/L increase in voriconazole.
Conclusions:
- Inflammation, as measured by CRP, is significantly associated with higher voriconazole trough concentrations.
- Inflammatory status may be a critical factor to consider in therapeutic drug monitoring of voriconazole.
- Further research is needed to evaluate the clinical utility of incorporating CRP levels for optimizing voriconazole dosing and preventing adverse events.
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