Lower Prealbumin and Higher CRP Increase the Risk of Voriconazole Overexposure and Adverse Reactions

Background: Voriconazole (VRZ) is a commonly used antifungal drug. However, the drug has nonlinear metabolic kinetic characteristics. Many factors can affect the plasma drug concentration, thus affecting the safety and effectiveness of VRZ. Objective: The aim of this study is to characterize the correlation between prealbumin (PA) or CRP and VRZ overexposure and adverse reactions. Methods: Patients who received VRZ as a treatment and performed therapeutic drug monitoring (TDM) were included. Biomarkers and combined medications were analyzed to find out factors that were related to VRZ trough concentrations (C(min)) and overexposure (C(min )>5.0 mg/L). Receiver operating characteristic (ROC) curves were used to determine the cut-off levels. Patients were divided into three groups according to different PA and CRP levels. Then, the 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 a cut-off level of 145.5 mg/L and 102.23 mg/L, respectively. Patients in Group 2 (PA <145.5 mg/L and CRP >102.23 mg/L) had an incidence rate of adverse reactions up to 70.27%, while the incidence rates in Group 1 (PA >145.5 mg/L and CRP <102.23 mg/L) and Group 3 (PA <145.5 mg/L and CRP <102.23 mg/L or PA >145.5 mg/L and CRP >102.23 mg/L) were 15.38% and 32.43%, respectively. 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 <145.5 mg/L and CRP >102.23 mg/L at the same time.