4.6 Review Book Chapter

Gene-Based Dose Optimization in Children

Journal

Publisher

ANNUAL REVIEWS
DOI: 10.1146/annurev-pharmtox-010919-023459

Keywords

pharmacogenomics; pediatrics; infectious disease; psychiatry; oncology; immunology

Funding

  1. Burroughs Wellcome Innovation in Regulatory Science [1015006]
  2. Doris Duke Clinical Scientist Development award [2017075]

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Phannacogenetics is a key component of precision medicine. Genetic variation in drug metabolism enzymes can lead to variable exposure to drugs and metabolites, potentially leading to inefficacy and drug toxicity. Although the evidence for pharmacogenetic associations in children is not as extensive as for adults, there are several drugs across diverse therapeutic areas with robust pediatric data indicating important, and relatively common, drug gene interactions. Guidelines to assist gene -based dose optimization are available for codeine, thiopurine drugs, selective serotonin reuptake inhibitors, atomoxetine, tacrolimus, and voriconazole. For each of these drugs, there is an opportunity to clinically implement precision medicine approaches with children for whom genetic test results are known or are obtained at the time of prescribing. For many more drugs that are commonly used in pediatric patients, additional investigation is needed to determine the genetic factors influencing appropriate dose.

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