Association of CYP2C19, CYP3A4 and ABCC2 polymorphisms and voriconazole plasma concentrations in Uygur pediatric patients

Pharmacogenomics. 2023 Feb;24(3):141-151. doi: 10.2217/pgs-2022-0159. Epub 2023 Jan 31.

Abstract

Aim: To evaluate the association between CYP2C19, CYP3A4 and ABCC2 polymorphisms and voriconazole plasma concentrations in Uygur pediatric patients with allogeneic hematopoietic stem cell transplantation. Materials & methods: High performance liquid chromatography-mass spectrometry was employed to monitor voriconazole concentrations. First-generation sequencing was performed to detect gene polymorphisms. Results: Voriconazole concentrations of normal metabolizers were significantly higher than those of intermediate (p < 0.05) and ultrafast (p < 0.001) metabolizers. Patients with ABCC2 GG and GA genotypes exhibited significantly lower voriconazole concentrations compared with patients with the AA genotype (p < 0.05). Conclusion: These results demonstrate a significant association between voriconazole concentrations and the CYP2C19 phenotype in Uygur pediatric patients with allogeneic hematopoietic stem cell transplantation.

Keywords: ABCC2; CYP2C19; CYP3A4; plasma concentrations; voriconazole.

MeSH terms

  • Antifungal Agents*
  • Cytochrome P-450 CYP2C19 / genetics
  • Cytochrome P-450 CYP3A* / genetics
  • Genotype
  • Humans
  • Multidrug Resistance-Associated Protein 2
  • Polymorphism, Genetic / genetics
  • Voriconazole / therapeutic use

Substances

  • Voriconazole
  • Antifungal Agents
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 CYP2C19
  • Multidrug Resistance-Associated Protein 2
  • CYP2C19 protein, human
  • CYP3A4 protein, human