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Challenges of pediatric pharmacotherapy: A narrative review of pharmacokinetics, pharmacodynamics, and pharmacogenetics

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Abstract

Purpose

Personalized pharmacotherapy, including for the pediatric population, provides optimal treatment and has emerged as a major trend owing to advanced drug therapeutics and diversified drug selection. However, it is essential to understand the growth and developmental characteristics of this population to provide appropriate drug therapy. In recent years, clinical pharmacogenetics has accumulated knowledge in pediatric pharmacotherapy, and guidelines from professional organizations, such as the Clinical Pharmacogenetics Implementation Consortium, can be consulted to determine the efficacy of specific drugs and the risk of adverse effects. However, the existence of a large knowledge gap hinders the use of these findings in clinical practice.

Methods

We provide a narrative review of the knowledge gaps in pharmacokinetics (PK) and pharmacodynamics (PD) in the pediatric population, focusing on the differences from the perspective of growth and developmental characteristics. In addition, we explored PK/PD in relation to pediatric clinical pharmacogenetics.

Results

The lack of direct and indirect biomarkers for more accurate assessment of the effects of drug administration limits the current knowledge of PD. In addition, incorporating pharmacogenetic insights as pivotal covariates is indispensable in this comprehensive synthesis for precision therapy; therefore, we have provided recommendations regarding the current status and challenges of personalized pediatric pharmacotherapy. The integration of clinical pharmacogenetics with the health care system and institution of educational programs for health care providers is necessary for its safe and effective implementation. A comprehensive understanding of the physiological and genetic complexities of the pediatric population will facilitate the development of effective and personalized pharmacotherapeutic strategies.

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  1. Department of Pediatrics and Child Health, Nihon University School of Medicine, 30-1 Kami-cho Ooyaguchi, Itabashi-ku, Tokyo, 173-8610, Japan

    Hirofumi Watanabe, Nobuhiko Nagano, Nobutaka Noto, Mamoru Ayusawa & Ichiro Morioka

  2. Laboratory of Clinical Pharmacometrics, School of Pharmacy, Nihon University, Chiba, Japan

    Yasuhiro Tsuji

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Writing—original draft preparation: Hirofumi Watanabe; Supervision: Nobuhiko Nagano, Yasuhiro Tsuji, Nobutaka Noto, Mamoru Ayusawa, and Ichiro Morioka.

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Watanabe, H., Nagano, N., Tsuji, Y. et al. Challenges of pediatric pharmacotherapy: A narrative review of pharmacokinetics, pharmacodynamics, and pharmacogenetics. Eur J Clin Pharmacol 80, 203–221 (2024). https://doi.org/10.1007/s00228-023-03598-x

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