在接受造血干细胞移植的泰国儿科患者中,根据模型对静脉注射布舒凡进行精确配药。

IF 2.8 4区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY
Apichaya Puangpetch, Fabienne Thomas, Usanarat Anurathapan, Samart Pakakasama, Suradej Hongeng, Jiratha Rachanakul, Santirhat Prommas, Nutthan Nuntharadthanaphong, Étienne Chatelut, Chonlaphat Sukasem, Félicien Le Louedec
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引用次数: 0

摘要

背景:在造血干细胞移植前,双功能调节剂--丁硫酚通常用于儿童。目前,泰国曼谷拉玛提博迪医院根据年龄和体表面积计算初始剂量,每天采集 7 个样本用于治疗药物监测(TDM)。本研究旨在根据患者特征先验地确定个体剂量的最佳策略,并根据 TDM 后验地确定个体剂量的最佳策略:药代动力学数据集包括135名泰国(n = 135)儿科患者(中位年龄 = 8岁)的2018年血浆浓度,并采用群体方法进行分析:体重、是否患有恶性疾病以及谷胱甘肽S-转移酶α-1(GSTA1)的基因多态性是预测清除率的因素。TDM浓度测量的最佳取样时间为输注3小时后的0.25、2和5小时。这足以获得贝叶斯估计的后验清除率。模拟结果表明,基于先验公式的剂量计算效果不佳,90% 的患者在目标值附近的暴露间隔为 69%-151%。如果仅在第 1 天进行 TDM,这一区间将缩小至 85%-124% ;如果在第 1 天和第 3 天进行 TDM,这一区间将缩小至 90%-116% :这项综合研究加强了治疗药物监测在管理个体间硫丹暴露变异性方面的作用。使用贝叶斯方法,可从 3 个样本中可靠地实施治疗药物监测,最好在 2 天内完成。如果无法使用贝叶斯方法,那么本文所开发的公式可作为泰国患者的替代方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Model-Informed Precision Dosing of Intravenous Busulfan in Thai Pediatrics Undergoing Hematopoietic Stem Cell Transplantation.

Background: Conditioning bifunctional agent, busulfan, is commonly used on children before hematopoietic stem cell transplantation. Currently, at the Ramathibodi hospital, Bangkok, Thailand, initial dosing is calculated according to age and body surface area, and 7 samples per day are used for therapeutic drug monitoring (TDM). This study aimed to identify the best strategies for individual dosages a priori from patient characteristics and a posteriori based on TDM.

Methods: The pharmacokinetic data set consisted of 2018 plasma concentrations measured in 135 Thai (n = 135) pediatric patients (median age = 8 years) and were analyzed using a population approach.

Results: Body weight, presence of malignant disease, and genetic polymorphism of Glutathione S-transferase Alpha-1 (GSTA1) were predictors of clearance. The optimum sampling times for TDM concentration measurements were 0.25, 2, and 5 hours after a 3-hour infusion. This was sufficient to obtain a Bayesian estimate of clearance a posteriori. Simulations showed the poor performance of a priori formula-based dose calculations with 90% of patients demonstrating a 69%-151% exposure interval around the target. This interval shrank to 85%-124% if TDM was carried out only at day 1 and to 90%-116% with TDM at days 1 and 3.

Conclusions: This comprehensive study reinforces the interest of TDM in managing interindividual variability in busulfan exposure. Therapeutic drug monitoring can reliably be implemented from 3 samples using the Bayesian approach, preferably over 2 days. If using the latter is not possible, the formulas developed herein could present an alternative in Thai patients.

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来源期刊
Therapeutic Drug Monitoring
Therapeutic Drug Monitoring 医学-毒理学
CiteScore
5.00
自引率
8.00%
发文量
213
审稿时长
4-8 weeks
期刊介绍: Therapeutic Drug Monitoring is a peer-reviewed, multidisciplinary journal directed to an audience of pharmacologists, clinical chemists, laboratorians, pharmacists, drug researchers and toxicologists. It fosters the exchange of knowledge among the various disciplines–clinical pharmacology, pathology, toxicology, analytical chemistry–that share a common interest in Therapeutic Drug Monitoring. The journal presents studies detailing the various factors that affect the rate and extent drugs are absorbed, metabolized, and excreted. Regular features include review articles on specific classes of drugs, original articles, case reports, technical notes, and continuing education articles.
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