Therapeutic Drug Monitoring of Voriconazole in Patients with End-Stage Liver Disease.

Background: This study aimed to identify the factors that influence voriconazole (VCZ) plasma concentrations and optimize the doses of VCZ in patients with end-stage liver disease (ESLD).

Methods: Patients with ESLD who received a VCZ maintenance dose of 100 mg twice daily (group A, n = 57) or the VCZ maintenance dose of 50 mg twice daily (group B, n = 37), orally or intravenously, were enrolled in this study. Trough plasma concentrations (Cmin) of VCZ between 1 and 5 mg/L were considered within the therapeutic target range.

Results: The VCZ Cmin was determined in 94 patients with ESLD. The VCZ Cmin of patients in group A was remarkably higher than those in group B (4.85 ± 2.53 mg/L vs 2.75 ± 1.40 mg/L; P < 0.001). Compared with group A, fewer patients in group B had VCZ Cmin outside the therapeutic target (23/57 vs. 6/37, P = 0.021). Univariate and multivariate analyses suggested that both body weight and Model for End-Stage Liver Disease scores were closely associated with the VCZ Cmin in group B.

Conclusions: These data indicate that dose optimization based on body weight and Model for End-Stage Liver Disease scores is required to strike an efficacy-safety balance during VCZ treatment in patients with ESLD.