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The Role of Plasma Trough Concentration of Voriconazole and Voriconazole N-Oxide in Its Hepatotoxicity in Adult Patients.
Cheng, Lin; You, Xi; Wang, Xiaowen; Yu, Mingjie; Jia, Changsheng.
Afiliación
  • Cheng L; Department of Pharmacy, the First Affiliated Hospital of Army Medical University, Chongqing, People's Republic of China.
  • You X; Department of Pharmacy, the First Affiliated Hospital of Army Medical University, Chongqing, People's Republic of China.
  • Wang X; Department of Pharmacy, the First Affiliated Hospital of Army Medical University, Chongqing, People's Republic of China.
  • Yu M; Department of Pharmacy, the First Affiliated Hospital of Army Medical University, Chongqing, People's Republic of China.
  • Jia C; Department of Pharmacy, the First Affiliated Hospital of Army Medical University, Chongqing, People's Republic of China.
Drug Des Devel Ther ; 18: 3617-3628, 2024.
Article en En | MEDLINE | ID: mdl-39156484
ABSTRACT

Objective:

Hepatotoxicity is an important cause of early withdrawal of voriconazole (VCZ). The role of the plasma trough concentration of VCZ (C0) in hepatotoxicity is confusion. VCZ N-oxide is the primary metabolite of VCZ in plasma. We investigated the role of VCZ C0 and plasma trough concentration of VCZ N-oxide (CN) in hepatotoxicity in adult patients. Materials and

Methods:

This was a prospective study. VCZ C0 and CN were measured using liquid chromatography-tandem mass spectrometry.

Results:

In total, 601 VCZ C0 and CN 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 C0 was a risk factor for grade 1 or higher adverse events of AST in elderly patients and TBIL in younger adult patients, and VCZ CN 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 C0 was higher than 4.0 µg/mL, or the VCZ CN was lower than 1.7 µg/mL, the incidence of grade 1 or higher adverse events of AST and TBIL increased.

Conclusion:

VCZ C0 and CN were associated with liver function-related adverse events. Measurement of VCZ CN should be considered for VCZ therapeutic drug monitoring.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad Hepática Inducida por Sustancias y Drogas / Voriconazol / Antifúngicos Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Drug Des Devel Ther Asunto de la revista: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Año: 2024 Tipo del documento: Article Pais de publicación: Nueva Zelanda

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad Hepática Inducida por Sustancias y Drogas / Voriconazol / Antifúngicos Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Drug Des Devel Ther Asunto de la revista: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Año: 2024 Tipo del documento: Article Pais de publicación: Nueva Zelanda