我们是否忽视了对儿童靶点药物暴露的研究?文献系统回顾

IF 4.6 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Eline Hermans, Jozefien Meersschaut, Isis Van herteryck, Mathias Devreese, Johan Vande Walle, Peter De Paepe, Pieter A. De Cock
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引用次数: 0

摘要

背景和目的理想情况下,药物剂量应根据目标部位的药物浓度来确定,而对于大多数药物来说,目标部位与组织相对应。生长发育对药物组织分布的确切影响尚不清楚。本系统综述汇编了目前有关儿童全身用药组织分布的知识,旨在确定该人群组织药代动力学(PK)研究的优先事项。大多数研究(83%)采用组织活检作为取样技术。最常检查的是扁桃体和/或腺样组织(占所有纳入患者的 70%)。大多数研究的样本量较小(中位数为 9,范围为 1-93),不包括最小年龄组(新生儿和婴儿),且报告质量较低。由于来自不同研究化合物、给药方案、人群和靶组织的数据各不相同,因此对不同研究的 PK 数据进行比较的可能性有限。随着安全研究儿童药物组织分布的技术的出现,应鼓励未来在这一领域的研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Have We Neglected to Study Target-Site Drug Exposure in Children? A Systematic Review of the Literature

Have We Neglected to Study Target-Site Drug Exposure in Children? A Systematic Review of the Literature

Background and Objective

Drug dosing should ideally be based on the drug concentrations at the target site, which, for most drugs, corresponds to the tissue. The exact influence of growth and development on drug tissue distribution is unclear. This systematic review compiles the current knowledge on the tissue distribution of systemically applied drugs in children, with the aim to identify priorities in tissue pharmacokinetic (PK) research in this population.

Methods

A systematic literature search was performed in the MEDLINE and Embase databases.

Results

Forty-two relevant articles were identified, of which 71% investigated antibiotics, while drug classes from the other studies were anticancer drugs, antifungals, anthelmintics, sedatives, thyreostatics, immunomodulators, antiarrhythmics, and exon skipping therapy. The majority of studies (83%) applied tissue biopsy as the sampling technique. Tonsil and/or adenoid tissue was most frequently examined (70% of all included patients). The majority of studies had a small sample size (median 9, range 1–93), did not include the youngest age categories (neonates and infants), and were of low reporting quality. Due to the heterogeneous data from different study compounds, dosing schedules, populations, and target tissues, the possibility for comparison of PK data between studies was limited.

Conclusion

The influence of growth and development on drug tissue distribution continues to be a knowledge gap, due to the paucity of tissue PK data in children, especially in the younger age categories. Future research in this field should be encouraged as techniques to safely investigate drug tissue disposition in children are available.

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来源期刊
CiteScore
8.80
自引率
4.40%
发文量
86
审稿时长
6-12 weeks
期刊介绍: Clinical Pharmacokinetics promotes the continuing development of clinical pharmacokinetics and pharmacodynamics for the improvement of drug therapy, and for furthering postgraduate education in clinical pharmacology and therapeutics. Pharmacokinetics, the study of drug disposition in the body, is an integral part of drug development and rational use. Knowledge and application of pharmacokinetic principles leads to accelerated drug development, cost effective drug use and a reduced frequency of adverse effects and drug interactions.
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