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持续肾脏替代治疗下危重症儿童的药物剂量优化:从基本概念到床边模型指导的精准给药

Drug dosing optimization in critically ill children under continuous renal replacement therapy: from basic concepts to the bedside model informed precision dosing.

作者信息

Oualha Mehdi, Thy Michael, Bouazza Naïm, Benaboud Sihem, Béranger Agathe

机构信息

Pediatric Intensive Care Unit, Necker Hospital, APHP-Centre, Université of Paris-Cité, Paris, France.

Pharmacology and drug evaluation in children and pregnant women, University of Paris-Cité, Hôpital Tarnier, Paris, France.

出版信息

Expert Opin Drug Metab Toxicol. 2025 Jan-Feb;21(2):173-190. doi: 10.1080/17425255.2024.2422875. Epub 2024 Nov 4.

Abstract

INTRODUCTION

Optimizing drug dosage in critically ill children undergoing Continuous Renal Replacement Therapy (CRRT) is mandatory and challenging, given the many factors impacting pharmacokinetics and pharmacodynamics coupled with the vulnerability of this population.

AREAS COVERED

A good understanding of the mechanisms that determine drug elimination via the CRRT technique is useful to avoid prescription pitfalls, however limited by the high between and within subject variability. The developments of population pharmacokinetic and physiologically based pharmacokinetic models derived from in-vivo and in-vitro studies, are challenging, but remain the most appropriate tool to suggest adjusted dosage regimens for every patient, throughout treatment. We searched PubMed using the search string: 'pediatrics OR children' AN 'continuous renal replacement therapy' AND 'pharmacokinetics' AND 'model informed precision dosing' AND, 'physiologically based pharmacokinetics,' AND 'therapeutic drug monitoring' until January 2024, regardless of language or publication status.

EXPERT OPINION

Familiarizing the pediatric intensivists with the therapeutic drug monitoring and providing clinicians the individualized prescribing software such as Model Informed Precision Dosing would be a significant step forward. The clinical benefit for patients remains to be demonstrated.

摘要

引言

鉴于影响药代动力学和药效学的诸多因素以及危重症儿童的脆弱性,优化接受持续肾脏替代疗法(CRRT)的危重症儿童的药物剂量是必要且具有挑战性的。

涵盖领域

深入了解通过CRRT技术决定药物清除的机制有助于避免处方失误,然而受个体间和个体内高度变异性的限制。源自体内和体外研究的群体药代动力学和基于生理的药代动力学模型的发展具有挑战性,但仍然是在整个治疗过程中为每位患者推荐调整剂量方案的最合适工具。我们在PubMed上使用搜索词:“儿科学或儿童”与“持续肾脏替代疗法”以及“药代动力学”以及“模型指导的精准给药”以及“基于生理的药代动力学”以及“治疗药物监测”进行搜索,截至2024年1月,不考虑语言或出版状态。

专家意见

让儿科重症监护医生熟悉治疗药物监测并为临床医生提供诸如模型指导的精准给药等个性化处方软件将是向前迈出的重要一步。对患者的临床益处仍有待证明。

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