Department of Pharmacy, the First Affiliated Hospital of Army Medical University, Chongqing, People's Republic of China.
Drug Des Devel Ther. 2024 Aug 13;18:3617-3628. doi: 10.2147/DDDT.S475706. eCollection 2024.
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.
This was a prospective study. VCZ C and C were measured using liquid chromatography-tandem mass spectrometry.
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.
VCZ C and C were associated with liver function-related adverse events. Measurement of VCZ C should be considered for VCZ therapeutic drug monitoring.
肝毒性是伏立康唑（VCZ）早期停药的一个重要原因。VCZ 血药谷浓度（C）在肝毒性中的作用存在争议。VCZ N-氧化物是 VCZ 在血浆中的主要代谢物。我们研究了成人患者中 VCZ C 和 VCZ N-氧化物（C）血药谷浓度与肝毒性的关系。
这是一项前瞻性研究。采用液相色谱-串联质谱法测定 VCZ C 和 C。
共纳入 376 例成年患者的 601 份 VCZ C 和 C 数据。ALP、ALT、AST、γ-GT 和 TBIL 中 1 级或以上不良事件的发生率分别为 35.4%、21.0%、30.1%、56.2%和 22.2%。与年轻成年患者相比，老年（≥65 岁）患者 ALP 1 级或以上不良事件发生率更高。多变量分析显示，VCZ C 是老年患者 AST 1 级或以上不良事件和年轻成年患者 TBIL 的危险因素，VCZ C 是 ALT、AST 和 TBIL 1 级或以上不良事件的危险因素。受试者工作特征曲线分析结果表明，当 VCZ C 高于 4.0μg/ml 或低于 1.7μg/ml 时，AST 和 TBIL 1 级或以上不良事件的发生率增加。
VCZ C 和 C 与肝功能相关不良事件有关。VCZ 治疗药物监测时应考虑测定 VCZ C。
