Predictors of Voriconazole Concentration in Hematopoietic Stem Cell Transplant

Abstract

The variability in individual response to voriconazole can be influenced by both genetic factors (pharmacogenetics) and clinical factors. Understanding the pharmacogenetic and clinical predictors of voriconazole response is important for optimizing its use and minimizing adverse effects. Patel and colleagues investigated the association of genetic polymorphisms in ABCB1, ABCG2, CYP2C9, CYP3A4, CYP3A5, and the CYP2C genes with voriconazole trough concentrations in patients receiving CYP2C19-guided dosing.  They performed a retrospective study in allogeneic hematopoietic cell transplant patients receiving CYP2C19-guided voriconazole dosing. They found that 36% of 185 patients were subtherapeutic. They also found that CYP2C19, age, and letermovir use were associated with voriconazole concentrations. Variations in the ABCG2 gene were associated with voriconazole concentrations in patients receiving 200 mg dose.  Genetic polymorphisms in CYP2C19 and letermovir use were associated with subtherapeutic status. They concluded that CYP2C19 phenotype and letermovir use were significantly associated with subtherapeutic voriconazole concentrations and may be used to improve voriconazole precision dosing. Pharmacogenomics J. 2023 Nov;23(6):201-209.  doi: 10.1038/s41397-023-00320-z.