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