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

ABSTRACT

In this brief report, we provide an analysis of the influence of a novel CYP2C haplotype (CYP2CTG) on proton pump inhibitor (PPI) pharmacokinetics (PK) in children. The CYP2CTG haplotype has been proposed to be associated with increased CYP2C19 activity. We sought to determine if this CYP2CTG 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 CYP2CTG 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 CYP2CTG 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 CYP2CTG allele after adjustment for the CYP2C19 genotype. We found the CYP2CTG 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 CYP2CTG haplotype to guide PPI dose adjustments in children.