British journal of clinical pharmacology · 2026
Impact of voriconazole/posaconazole on CsA in paediatric allogeneic haematopoietic stem cell transplantation recipients: A real-world study.
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Jia Meng-Meng, Wang Dao, Yang Jing
Аннотация
AIMS: The aim of this study is to investigate the key factors influencing the extent of DDI between cyclosporine A (CsA, GtoPdb Ligand ID: 2162) and voriconazole (VCZ, GtoPdb Ligand ID: 6424)/posaconazole (PCZ, GtoPdb Ligand ID: 6426) in Chinese paediatric allo-HSCT recipients and to establish evidence-based dose adjustment strategies.
METHODS: One-hundred-four children were enrolled and already taking stable doses of oral CsA when voriconazole or posaconazole was initiated. Evaluate the CsA dose and body weight-adjusted dose-normalized concentration (C/D) required to achieve therapeutic trough concentration (Cmin) before and after initiation of voriconazole or posaconazole.
RESULTS: CsA C/D increased by 173.37% during VCZ co-therapy and 132.90% during PCZ co-therapy. The magnitude of change in CsA C/D was significantly associated with CYP2C19 (GtoPdb Enzyme ID: 1043) genotype and PCZ Cmin. For maintaining therapeutic CsA exposure, the required percentage reduction in CsA dose varied according to CYP3A5 (GtoPdb Enzyme ID: 1040) genotype and age. In the VCZ group, dose reductions ranged from 22.22% to 43.47% across age and CYP3A5 genotype subgroups. In the PCZ group, dose reductions ranged from 12.77% to 33.34% across corresponding subgroups.
CONCLUSION: CYP2C19 genotype and PCZ Cmin independently affect the magnitude of the DDI between CsA and VCZ/PCZ in paediatric allo-HSCT patients, and CYP3A5 genotype and age of children should be integrated to guide individualized CsA dose reduction when co-administered with VCZ or PCZ.
METHODS: One-hundred-four children were enrolled and already taking stable doses of oral CsA when voriconazole or posaconazole was initiated. Evaluate the CsA dose and body weight-adjusted dose-normalized concentration (C/D) required to achieve therapeutic trough concentration (Cmin) before and after initiation of voriconazole or posaconazole.
RESULTS: CsA C/D increased by 173.37% during VCZ co-therapy and 132.90% during PCZ co-therapy. The magnitude of change in CsA C/D was significantly associated with CYP2C19 (GtoPdb Enzyme ID: 1043) genotype and PCZ Cmin. For maintaining therapeutic CsA exposure, the required percentage reduction in CsA dose varied according to CYP3A5 (GtoPdb Enzyme ID: 1040) genotype and age. In the VCZ group, dose reductions ranged from 22.22% to 43.47% across age and CYP3A5 genotype subgroups. In the PCZ group, dose reductions ranged from 12.77% to 33.34% across corresponding subgroups.
CONCLUSION: CYP2C19 genotype and PCZ Cmin independently affect the magnitude of the DDI between CsA and VCZ/PCZ in paediatric allo-HSCT patients, and CYP3A5 genotype and age of children should be integrated to guide individualized CsA dose reduction when co-administered with VCZ or PCZ.