The Role of Plasma Trough Concentration of Voriconazole and Voriconazole N-Oxide in Its Hepatotoxicity in Adult Patients.

OBJECTIVE

Hepatotoxicity is an important cause of early withdrawal of voriconazole (VCZ). The role of the plasma trough concentration of VCZ (C) in hepatotoxicity is confusion. VCZ N-oxide is the primary metabolite of VCZ in plasma. We investigated the role of VCZ C and plasma trough concentration of VCZ N-oxide (C) in hepatotoxicity in adult patients.

MATERIALS AND METHODS

This was a prospective study. VCZ C and C were measured using liquid chromatography-tandem mass spectrometry.

RESULTS

In total, 601 VCZ C and C from 376 adult patients were included. The percentage of grade 1 or higher adverse events for ALP, ALT, AST, γ-GT, and TBIL were 35.4%, 21.0%, 30.1%, 56.2%, and 22.2%, respectively. Compared with younger adult patients, elderly patients (≥65 years) had a higher rate of grade 1 or higher adverse events of ALP. In the multivariate analysis, VCZ C was a risk factor for grade 1 or higher adverse events of AST in elderly patients and TBIL in younger adult patients, and VCZ C was a risk factor for grade 1 or higher adverse events of ALT, AST, and TBIL. Results of the receiver operating characteristic curve analysis indicated that when the VCZ C was higher than 4.0 μg/mL, or the VCZ C was lower than 1.7 μg/mL, the incidence of grade 1 or higher adverse events of AST and TBIL increased.

CONCLUSION

VCZ C and C were associated with liver function-related adverse events. Measurement of VCZ C should be considered for VCZ therapeutic drug monitoring.