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Perspectives from the Society for Pediatric Research: pharmacogenetics for pediatricians

Abstract

This review evaluates the pediatric evidence for pharmacogenetic associations for drugs that are commonly prescribed by or encountered by pediatric clinicians across multiple subspecialties, organized from most to least pediatric evidence. We begin with the pharmacogenetic research that led to the warning of increased risk of death in certain pediatric populations (“ultrarapid metabolizers”) who are prescribed codeine after tonsillectomy or adenoidectomy. We review the evidence for genetic testing for thiopurine metabolism, which has become routine in multiple pediatric subspecialties. We discuss the pharmacogenetic research in proton pump inhibitors, for which clinical guidelines have recently been made available. With an increase in the prevalence of behavioral health disorders including attention deficit hyperactivity disorder (ADHD), we review the pharmacogenetic literature on selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors, and ADHD medications. We will conclude this section on the current pharmacogenetic data on ondansetron. We also provide our perspective on how to integrate the current research on pharmacogenetics into clinical care and what further research is needed. We discuss how institutions are managing pharmacogenetic test results and implementing them clinically, and how the electronic health record can be leveraged to ensure testing results are available and taken into consideration when prescribing medications.

Impact

  • While many reviews of pharmacogenetics literature are available, there are few focused on pediatrics.

  • Pediatricians across subspecialties will become more comfortable with pharmacogenetics terminology, know resources they can use to help inform their prescribing habits for drugs with known pharmacogenetic associations, and understand the limitations of testing and where further research is needed.

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Fig. 1: The relationship between prodrugs, active drugs, inactivated drug metabolites, and metabolizer status.
Fig. 2: A timeline of pharmacogenetic testing to demonstrate preemptive vs. reactive testing.

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Acknowledgements

We thank Brendan (Tex) Armstreet for assistance with designing Fig. 1, and Drs. Catherine Forster and Todd Florin for critical feedback on this manuscript. Figures were created with Biorender.com. S.C.T.G. was supported by the National Institute of Child Health and Development Cincinnati Pediatric Clinical Pharmacology Postdoctoral Training Program [5T32HD069054–09] and K.M.R. was supported by the National Institute of Child Health and Development & National Institute of General Medical Sciences Vanderbilt Pediatric Clinical Pharmacology Postdoctoral Training Program [5T32GM007569–43].

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Tang Girdwood, S.C., Rossow, K.M., Van Driest, S.L. et al. Perspectives from the Society for Pediatric Research: pharmacogenetics for pediatricians. Pediatr Res 91, 529–538 (2022). https://doi.org/10.1038/s41390-021-01499-2

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