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儿童药物剂量的药物基因组学:当前的使用、知识和差距。

Pharmacogenomics for Drug Dosing in Children: Current Use, Knowledge, and Gaps.

机构信息

Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, USA.

Division of General Internal Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

出版信息

J Clin Pharmacol. 2021 Jun;61 Suppl 1(Suppl 1):S188-S192. doi: 10.1002/jcph.1891.

Abstract

Pharmacogenomics research ranges from the discovery of genetic factors to explain interpatient variability in drug exposure and response to clinical implementation of this knowledge to improve pharmacotherapy. Medications with actionable pharmacogenomic associations are frequently used in children, and therefore pharmacogenomics-guided precision medicine is readily applicable to the pediatric population. Although heritable genetics are considered immutable, the impact of genetic variation in pharmacogenes is modified by other factors such as age-dependent changes in gene expression. Early evidence has emerged indicating that the interaction between ontogeny and pharmacogenomics determines whether or how genetics-based dosing algorithms should be adjusted in children versus adults. However, there is still a paucity of data describing pharmacogenomic associations in patient populations across the life span. Future research is much needed to evaluate the impact of pharmacogenomics on drug dosing specific to the pediatric population, along with consideration of other developmental and physiological factors uniquely related to drug disposition in this population.

摘要

药物基因组学研究范围从发现遗传因素解释药物暴露和反应的个体间变异性到临床实施这些知识以改善药物治疗。具有可操作的药物基因组学关联的药物经常用于儿童,因此药物基因组学指导的精准医学很容易适用于儿科人群。尽管遗传性遗传被认为是不可改变的,但药物基因中的遗传变异的影响会受到其他因素的影响,例如基因表达的年龄依赖性变化。早期证据表明,个体发生和药物基因组学之间的相互作用决定了是否以及如何根据遗传基础调整儿童和成人的剂量算法。然而,仍然缺乏描述整个生命周期患者群体中药物基因组学关联的数据。未来的研究非常有必要评估药物基因组学对儿科人群药物剂量的影响,同时考虑与该人群药物处置相关的其他发育和生理因素。

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