Therapeutic Drug Monitoring of Voriconazole: Unbound Concentration With Clinical Efficacy and Adverse Events

Abstract

Background:

Voriconazole is widely used for patients with fungal infections, but the correlations between the unbound concentration (C_free) of voriconazole in plasma and clinical outcomes remains unclear.

Objective:

The aim of this study was to analyze the correlation between C_free and clinical outcomes.

Methods:

A retrospective analysis was conducted at the Second Hospital of Hebei Medical University from February 2021 to March 2024 (Shijiazhuang, China). Patients who received voriconazole with at least one measured concentration in our center were enrolled. Based on determined the C_free of voriconazole, factors that might affect C_free were analyzed in conjunction with patient characteristics, and the correlations between voriconazole C_free and the clinical efficacy as well as AEs in patients were investigated.

Results:

A total of 60 blood samples were collected from 56 patients. Voriconazole C_free was positive correlation with creatinine, while negative correlation with creatinine clearance. The C_free of patients in the clinical effective group was significantly higher than that in the clinical ineffective group, and the C_free of patients in the group with AEs was significantly higher than that in the group without AEs (P = 0.006, 0.025). Voriconazole C_free (odds ratio [OR] = 2.617, 95% confidence interval [CI]:1.142-6.000, P = 0.023) and albumin level (OR = 1.085, 95% CI: 1.000-1.177, P = 0.050) were independent influencing factors of clinical efficacy, the receiver operating characteristic (ROC) cut off for C_free and efficacy was 0.8 μg·mL⁻¹. Voriconazole C_free (OR = 1.979, 95% CI: 1.008-3.888, P = 0.048) was an independent risk factor for AEs, the ROC cut off for C_free and AEs was 1.2 μg·mL⁻¹.

Conclusions and relevance:

Voriconazole C_free was positively correlated with clinical efficacy and the incidence of AEs in patients.