Influence of novel CYP2C-haplotype on proton pump inhibitor pharmacokinetics in children

Clin Transl Sci. 2024 Apr;17(4):e13782. doi: 10.1111/cts.13782.

Abstract

In this brief report, we provide an analysis of the influence of a novel CYP2C haplotype (CYP2C:TG) on proton pump inhibitor (PPI) pharmacokinetics (PK) in children. The CYP2C:TG haplotype has been proposed to be associated with increased CYP2C19 activity. We sought to determine if this CYP2C:TG haplotype resulted in similar alterations in metabolism for proton pump inhibitors, which are primarily metabolized by CYP2C19. In a cohort of 41 children aged 6-21 participating in a PPI pharmacokinetic study, effects of the CYP2C:TG allele were assessed by fitting two linear regression models for each of the six PK outcomes assessed, the second of which accounted for the presence of the CYP2C:TG allele. The difference in R2 values between the two models was computed to quantify the variability in the outcome that could be accounted for by the CYP2C:TG allele after adjustment for the CYP2C19 genotype. We found the CYP2C:TG haplotype to have no measurable additive impact on CYP2C19-mediated metabolism of PPIs in vivo in older children and adolescents. The findings of this study do not support the clinical utility of routine testing for the CYP2C:TG haplotype to guide PPI dose adjustments in children.

MeSH terms

  • Adolescent
  • Aryl Hydrocarbon Hydroxylases* / genetics
  • Child
  • Cytochrome P-450 CYP2C19 / genetics
  • Cytochrome P-450 Enzyme System*
  • Genotype
  • Haplotypes
  • Humans
  • Proton Pump Inhibitors* / pharmacokinetics

Substances

  • cytochrome P-450 CYP2C subfamily
  • Proton Pump Inhibitors
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 Enzyme System