Pharmacogenetic of voriconazole antifungal agent in pediatric patients

Pharmacogenomics. 2018 Jul 1;19(11):913-925. doi: 10.2217/pgs-2017-0173. Epub 2018 Jun 19.

Abstract

Aim: We explored the role of SNPs within the SLCO1B3, SLCO1B1, SLC22A6, ABCB1, ABCG2, SLCO3A1, CYP2C19, ABCC2, SLC22A1, ABCB11 and NR1I2 genes on voriconazole pharmacokinetics.

Patients & methods: 233 pediatric patients were enrolled. Drug plasma Ctrough was measured by a HPLC-MS method. Allelic discrimination was performed by qualitative real-time PCR.

Results: SLCO1B3 rs4149117 c.334 GT/TT (p = 0.046), ABCG2 rs13120400 c.1194 + 928 CC (p = 0.029) and ABCC2 rs717620 c.-24 GA/AA (p = 0.025) genotype groups significantly influenced Ctrough. ethnicity (p = 0.042), sex (p = 0.033), SLCO1B3 rs4149117 c.334 GT/TT (p = 0.041) and ABCB1 rs1045642 c.3435 TT (p = 0.016) have been retained in linear regression model as voriconazole predictor factors.

Conclusion: Understanding how some gene polymorphisms affect the voriconazole pharmacokinetic is essential to optimally dose this agent.

Keywords: ABCB1; ABCC2; ABCG2; SLCO1B3; therapeutic drug monitoring; triazoles.

MeSH terms

  • Adolescent
  • Antifungal Agents / therapeutic use*
  • Child
  • Female
  • Genotype
  • Humans
  • Male
  • Multidrug Resistance-Associated Protein 2
  • Pharmacogenetics / methods
  • Pharmacogenomic Testing / methods
  • Polymorphism, Single Nucleotide / genetics
  • Voriconazole / therapeutic use*

Substances

  • ABCC2 protein, human
  • Antifungal Agents
  • Multidrug Resistance-Associated Protein 2
  • Voriconazole