Positive correlation between voriconazole trough concentrations and C-reactive protein levels in patients with chronic pulmonary aspergillosis: A retrospective cohort study

Voriconazole (VRCZ) is the first-line treatment for chronic pulmonary aspergillosis (CPA). VRCZ trough concentration monitoring is recommended for adequate therapy because VRCZ concentrations vary widely. However, factors associated with variations in VRCZ concentrations, especially in the same patient at different time points, have not been identified. The objective of this study was to identify factors influencing VRCZ trough concentrations.This single-center retrospective study conducted at our institute between April 2014 and August 2016 included patients with CPA who received VRCZ. Patient trough concentrations were measured more than twice while the patients received the same dose using the same administration route (defined as one series). A step-wise method and multiple regression analysis were used to test the effects of patient characteristics on VRCZ trough concentrations.Sixty-nine series in 49 patients were analyzed. VRCZ was administered orally in 59 series, intravenously in 7 series, and by dry syrup in 3 series. The median VRCZ trough concentration and the median variation in VRCZ concentrations were 1.68 and 0.99 μg/ml, respectively. In the simple regression analysis, creatinine, alkaline phosphatase, C-reactive protein (CRP), and creatinine clearance significantly correlated with VRCZ concentrations. Multiple regression analysis demonstrated a significant positive correlation between CRP and VRCZ concentration (P < 0.0001).In patients with CPA, VRCZ concentration correlated with CRP levels in the same patients receiving the same dose of VRCZ at different time points.