CYP51A1 polymorphism and voriconazole-associated hepatotoxicity in children undergoing hematopoietic cell transplant.
Int J Clin Pharmacol Ther
; 59(6): 442-446, 2021 Jun.
Article
em En
| MEDLINE
| ID: mdl-33560212
ABSTRACT
Fungal CYP51A (14α-sterol demethylase) is the target of an azole antifungal, voriconazole (VCZ), which also partially inhibits human CYP51A1. Hepatotoxicity is a common adverse effect of azoles, which is reported to be caused by altered gene expressions secondary to cholesterol synthesis inhibition by azoles. This is a post-hoc analysis of a previously conducted phase 1 dose-finding study of prophylactic VCZ in 56 pediatric hematopoietic cell transplant recipients. We explored an association between variants in human CYP51A1 (rs2282976 and rs6465348) and VCZ-induced hepatotoxicity. Genotype A/G or G/G in rs6465348 showed lower odds of hepatotoxicity after adjusting for VCZ area-under-the-curve (OR 0.10, 95% CI 0.01 - 0.79, vs. A/A).
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transplante de Células-Tronco Hematopoéticas
/
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos
/
Doença Hepática Induzida por Substâncias e Drogas
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Child
/
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article