Lower prealbumin and higher CRP increased the risk of Voriconazole overexposure and adverse reactions

Background: Voriconazole(VRZ) is a commonly used antifungal drug showing significant individual differences and narrow therapeutic window.The aim of this study is to characterize the correlation between prealbumin(PA) or C-reactive protein (CRP) and Voriconazole(VRZ) overexposure and adverse reactions. Methods Patients received VRZ as prevention or treatment and performed therapeutic drug monitoring (TDM) were included. Biomarkers and combined medication were analyzed to find out factors that related to VRZ trough concentrations (C min ) and overexposure (C min >5.0mg/L).ROC curves were used to determine the cut-off levels.Patients were divided into three groups according to different PA and CRP levels. Then incidence rate of VRZ adverse reactions between groups was analyzed. Results A total of 123 patients were included in the study. PA was negatively correlated,while CRP was positively correlated with VRZ concentrations.Lower PA or higher CRP was related to VRZ overexposure with the cut-off level of 145.5mg/L and 102.23mg/L respectively.Patients in group 2(PA  102.23mg/L) had a incidence rete of adverse reactions up to 70.27%,while incidence rate in group1(PA > 145.5mg/L and CRP < 102.23mg/L) and group 3(PA < 145.5mg/L and CRP  145.5mg/L and CRP > 102.23mg/L) were 15.38% and 32.43%. Conclusions PA and CRP were both related to VRZ concentrations and overexposure. The risk of VRZ overexposure and adverse reactions significantly increased in patients with PA  102.23mg/L at the same time.