Population Pharmacokinetics and Dose Optimization of Piperacillin in Infants and Children with Pneumonia.

IF 3.4 3区医学 Q1 PEDIATRICS Pediatric Drugs Pub Date : 2024-11-27 DOI:10.1007/s40272-024-00664-4

Totsapol Jirasomprasert, Li-Yuan Tian, Dian-Ping You, Ya-Kun Wang, Lei Dong, Ya-Hui Zhang, Guo-Xiang Hao, John van den Anker, Yue-E Wu, Bo-Hao Tang, Wei Zhao, Yi Zheng

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Abstract

Objective: We aimed to determine the piperacillin disposition and optimize the dosing regimens for infants and children with pneumonia.

Methods: An opportunistic sampling strategy was used in this pharmacokinetic study. High-performance liquid chromatography was used to measure the concentrations of piperacillin in plasma samples. A population pharmacokinetic model was conducted using NONMEM.

Results: The pharmacokinetic data of 90 samples from 64 infants and children with pneumonia (age range: 0.09-1.72 years for infants and 2.12-11.10 years for children) were available. A two-compartment model with first-order elimination was the most suitable model to describe the population pharmacokinetics of piperacillin. A covariate analysis indicated that body weight and age were significant factors affecting clearance. Monte Carlo simulations showed that a 50-mg/kg every 8 h or every 12 h dosing regimen results in underdosing. Results both in infants and children showed that an extended infusion (3 h) of various dosing regimens (80, 100, or 130 mg/kg) three times daily or a 300-mg/kg continuous infusion can reach a therapeutic level based on the chosen target for the probability of target attainment threshold of 70%, 80%, and 90% at minimum inhibitory concentration breakpoints of 8 mg/L and 16 mg/L.

Conclusions: A population pharmacokinetic model was obtained to evaluate the disposition of piperacillin, and the optimal dosing regimens were provided for use in infants and children with pneumonia.

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哌拉西林在婴幼儿肺炎患者中的群体药代动力学与剂量优化

目的我们旨在确定哌拉西林的处置，并优化肺炎婴幼儿的用药方案：方法：本药代动力学研究采用了机会性采样策略。方法：这项药代动力学研究采用了机会性采样策略，使用高效液相色谱法测量血浆样本中哌拉西林的浓度。使用 NONMEM 建立了群体药代动力学模型：结果：64 名患肺炎的婴儿和儿童（年龄范围：婴儿 0.09-1.72 岁，儿童 2.12-11.10 岁）的 90 份样本的药代动力学数据可用。一阶消除的二室模型是描述哌拉西林群体药代动力学的最合适模型。协变量分析表明，体重和年龄是影响清除率的重要因素。蒙特卡洛模拟显示，每 8 小时或每 12 小时给药 50 毫克/千克的方案会导致给药不足。对婴儿和儿童的研究结果表明，在最低抑制浓度断点为 8 毫克/升和 16 毫克/升的情况下，延长输注时间（3 小时），采用不同的给药方案（80、100 或 130 毫克/千克），每天三次，或连续输注 300 毫克/千克，可达到基于所选目标的治疗水平，达到目标的概率阈值分别为 70%、80% 和 90%：结论：我们建立了一个群体药代动力学模型来评估哌拉西林的处置，并提供了用于婴幼儿肺炎患者的最佳给药方案。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pediatric Drugs PEDIATRICS-PHARMACOLOGY & PHARMACY

CiteScore

7.20

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Pediatric Drugs promotes the optimization and advancement of all aspects of pharmacotherapy for healthcare professionals interested in pediatric drug therapy (including vaccines). The program of review and original research articles provides healthcare decision makers with clinically applicable knowledge on issues relevant to drug therapy in all areas of neonatology and the care of children and adolescents. The Journal includes: -overviews of contentious or emerging issues. -comprehensive narrative reviews of topics relating to the effective and safe management of drug therapy through all stages of pediatric development. -practical reviews covering optimum drug management of specific clinical situations. -systematic reviews that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. -Adis Drug Reviews of the properties and place in therapy of both newer and established drugs in the pediatric population. -original research articles reporting the results of well-designed studies with a strong link to clinical practice, such as clinical pharmacodynamic and pharmacokinetic studies, clinical trials, meta-analyses, outcomes research, and pharmacoeconomic and pharmacoepidemiological studies. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Pediatric Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.