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Pharmacogenetic Aspects of Drug Metabolizing Enzymes and Transporters in Pediatric Medicine: Study Progress, Clinical Practice and Future Perspectives

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Abstract

As the activity of certain drug metabolizing enzymes or transporter proteins can vary with age, the effect of ontogenetic and genetic variation on the activity of these enzymes is critical for the accurate prediction of treatment outcomes and toxicity in children. This makes pharmacogenetic research in pediatrics particularly important and urgently needed, but also challenging. This review summarizes pharmacogenetic studies on the effects of genetic polymorphisms on pharmacokinetic parameters and clinical outcomes in pediatric populations for certain drugs, which are commonly prescribed by clinicians across multiple therapeutic areas in a general hospital, organized from those with the most to the least pediatric evidence among each drug category. We also further discuss the research status of the gene-guided dosing regimens and clinical implementation of pediatric pharmacogenetics. More and more drug–gene interactions are demonstrated to have clinical validity for children, and pharmacogenomics in pediatrics have shown evidence-based benefits to enhance the efficacy and precision of existing drug dosing regimens in several therapeutic areas. However, the most important limitation to the implementation is the lack of high-quality, rigorous pediatric prospective clinical studies, so adequately powered interventional clinical trials that support incorporation of pharmacogenetics into the care of children are still needed.

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Authors and Affiliations

  1. Department of Pharmacy, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China

    Jinxia Zhao, Jialu Bian, Yinyu Zhao, Yuanyuan Li, Boyu Liu, Xu Hao, Shiyu He & Lin Huang

  2. Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China

    Jinxia Zhao, Jialu Bian, Yinyu Zhao & Shiyu He

  3. School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211198, China

    Yuanyuan Li & Xu Hao

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  1. Jinxia Zhao
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This work was supported by the Beijing Municipal Natural Science Foundation (grant number 7192218).

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Jinxia Zhao, Jialu Bian, Yinyu Zhao, Yuanyuan Li, Boyu Liu, Xu Hao, Shiyu He, and Lin Huang declare that they have no conflict of interest that might be relevant to the contents of this article.

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LH contributed to the study conception and design. Material preparation, data collection and analysis were performed by JZ, JB and YZ. The first draft of the manuscript was written by JZ and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Zhao, J., Bian, J., Zhao, Y. et al. Pharmacogenetic Aspects of Drug Metabolizing Enzymes and Transporters in Pediatric Medicine: Study Progress, Clinical Practice and Future Perspectives. Pediatr Drugs 25, 301–319 (2023). https://doi.org/10.1007/s40272-023-00560-3

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