Managing Voriconazole Exposure During Severe Infection; Effect of Inflammation on Voriconazole Metabolic Ratio

Voriconazole is a broad-spectrum antifungal agent. There is evidence for a relation between the efficacy and safety of voriconazole and voriconazole trough concentrations. There are several factors that could influence voriconazole concentrations. Inflammation could be one of these factors. In a retrospective study was observed that reduced metabolism of voriconazole was related to inflammation in patients with severe infections. Reduced metabolism of voriconazole resulted in high voriconazole levels and low N-oxide metabolite (inactive metabolite of voriconazole) levels. The purpose of this study is to determine an algorithm to guide dosing of voriconazole during severe inflammation and to develop a multiple linear regression model to describe the contribution of CRP concentrations to the variability in voriconazole levels and metabolic ratio.