Therapeutic drug monitoring and safety of voriconazole in patients with liver dysfunction.

Abstract

This study aims to describe the distribution characteristics of voriconazole (VRC) plasma trough concentrations (C_trough) in patients with liver dysfunction, identify factors influencing VRC C_trough, and provide recommendations for the use of VRC in this population. We retrospectively collected medical records of hospitalized patients with liver dysfunction who used VRC and underwent therapeutic drug monitoring (TDM) at the First Hospital of Changsha. The severity of liver dysfunction was assessed by the Child-Pugh (CP) score. Multiple linear regression was employed to explore factors affecting VRC C_trough in these patients. A total of 147 C_trough from 102 patients with liver dysfunction were analyzed. Patients were categorized into a control group (n = 40), CP-A (n = 39), CP-B (n = 11), and CP-C group (n = 12). The initial probability of target attainment of C_trough was 70.6%, with 6.9% of patients obtaining subtherapeutic C_trough and 22.5% obtaining supertherapeutic C_trough. The initial C_trough in CP-A and B were 5.05 (0.64-9.57) mg/L and 5.37 (0.26-10.01) mg/L, respectively, significantly higher than the control group (P = 0.021 and P = 0.010). The proportion of VRC C_trough of >5.5 mg/L in CP-A and B was 33.3% and 45.5%, respectively. Multiple linear regression analysis revealed that factors such as age ≥70 years, CP class, C-reactive protein (CRP), and direct bilirubin were significantly related to the initial VRC C_trough. Among all measurements, patients with severe inflammation (CRP >100 mg/L), aged ≥70 years, and albumin levels of <30 or <25 g/L had significantly higher VRC C_trough. The treatment success rate of VRC was 69.6% (71 of 102), and the rate of VRC-related adverse drug reactions was 29.4% (30 of 102). The recommended half-maintenance dose may lead to elevated VRC C_trough in patients with CP-A and CP-B. TDM is essential for patients with advanced age, severe infections, or hypoalbuminemia to prevent excessive VRC trough levels.