CYP51A1 polymorphism and voriconazole-associated hepatotoxicity in children undergoing hematopoietic cell transplant
Open Access
- 1 June 2021
- journal article
- research article
- Published by Dustri-Verlag Dr. Karl Feistle in International journal of clinical pharmacology and therapeutics
- Vol. 59 (06), 442-446
- https://doi.org/10.5414/cp203920
Abstract
Fungal CYP51A (14 alpha-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).Keywords
This publication has 8 references indexed in Scilit:
- A phase I dose finding study of intravenous voriconazole in pediatric patients undergoing hematopoietic cell transplantationBone Marrow Transplantation, 2019
- Comparative omics analyses of hepatotoxicity induced by oral azole drugs in mice liver and primary hepatocytesToxicology Mechanisms and Methods, 2019
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP2C19 and Voriconazole TherapyCancer Cell, 2016
- Trough concentration of voriconazole and its relationship with efficacy and safety: a systematic review and meta-analysisJournal of Antimicrobial Chemotherapy, 2016
- Polymorphisms of CYP51A1 from Cholesterol Synthesis: Associations with Birth Weight and Maternal Lipid Levels and Impact on CYP51 Protein StructurePLOS ONE, 2013
- Azole Affinity of Sterol 14α-Demethylase (CYP51) Enzymes from Candida albicans and Homo sapiensAntimicrobial Agents and Chemotherapy, 2013
- Multiplex Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Quantification in Human Plasma of Fluconazole, Itraconazole, Hydroxyitraconazole, Posaconazole, Voriconazole, Voriconazole- N -Oxide, Anidulafungin, and CaspofunginAntimicrobial Agents and Chemotherapy, 2010
- Drug-induced liver injury: Is it somehow foreseeable?World Journal of Gastroenterology, 2009