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

Kathryn E Kyler1,2, Andrea Gaedigk2,3, Susan Abdel-Rahman2

  • 1Division of Hospital Medicine, Children's Mercy Kansas City, Kansas City, Missouri, USA.

Clinical and Translational Science
|April 17, 2024
PubMed

Insights

The CYP2C:TG haplotype does not impact proton pump inhibitor (PPI) metabolism in children. Routine genetic testing for this variant is not clinically useful for guiding PPI dosing in pediatric patients.

Area of Science:

  • Pharmacogenomics
  • Drug Metabolism
  • Pediatric Pharmacology

Background:

  • Proton pump inhibitors (PPIs) are crucial for treating acid-related disorders in children.
  • CYP2C19 is the primary enzyme responsible for metabolizing many PPIs.
  • A novel CYP2C haplotype, CYP2C:TG, has been suggested to increase CYP2C19 activity.

Purpose of the Study:

  • To investigate the influence of the CYP2C:TG haplotype on the pharmacokinetics (PK) of proton pump inhibitors in children.
  • To determine if the CYP2C:TG haplotype alters PPI metabolism mediated by CYP2C19 in a pediatric population.

Main Methods:

  • Analysis of a cohort of 41 children (aged 6-21) enrolled in a PPI pharmacokinetic study.
  • Linear regression models were used to assess the effect of the CYP2C:TG allele on six PK outcomes.
  • Model comparison quantified the variability explained by the CYP2C:TG allele after adjusting for CYP2C19 genotype.

Main Results:

  • The CYP2C:TG haplotype demonstrated no significant additive impact on CYP2C19-mediated PPI metabolism in vivo.
  • The presence of the CYP2C:TG allele did not explain additional variability in PPI pharmacokinetics beyond CYP2C19 genotype.

Conclusions:

  • Findings do not support the routine clinical utility of testing for the CYP2C:TG haplotype to guide PPI dose adjustments in children.
  • The CYP2C:TG haplotype does not appear to be a significant determinant of PPI pharmacokinetics in older children and adolescents.

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