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

Creator(s)

Kathyrn Kyler, Children's Mercy HospitalFollow
Andrea Gaedigk, Children's Mercy Kansas CityFollow
Susan Abdel-Rahman
Vincent S. Staggs
Robin E. Pearce
Paul C. Toren, Children's Mercy HospitalFollow
J Steven Leeder, Children's Mercy HospitalFollow
Valentina Shakhnovich

Document Type

Article

Publication Date

4-2024

Identifier

DOI: 10.1111/cts.13782; PMCID: PMC11022290

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.

Journal Title

Clin Transl Sci

Volume

17

Issue

4

First Page

13782

Last Page

13782

MeSH Keywords

Child; Humans; Adolescent; Proton Pump Inhibitors; Haplotypes; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C19; Genotype; Cytochrome P-450 Enzyme System

Keywords

Proton Pump Inhibitors; Haplotypes; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C19; Genotype; Cytochrome P-450 Enzyme System

Comments

Grants and funding

• K23 DK115827/DK/NIDDK NIH HHS/United States
• T32 HD069038/HD/NICHD NIH HHS/United States

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Publisher's Link: https://ascpt.onlinelibrary.wiley.com/doi/10.1111/cts.13782

Recommended Citation

Kyler KE, Gaedigk A, Abdel-Rahman S, et al. Influence of novel CYP2C-haplotype on proton pump inhibitor pharmacokinetics in children. Clin Transl Sci. 2024;17(4):e13782. doi:10.1111/cts.13782