An Evaluation Approach for the Performance of Dosing Regimens in Attention-Deficit/Hyperactivity Disorder Treatment
An Evaluation Approach for the Performance of Dosing Regimens in Attention-Deficit/Hyperactivity Disorder Treatment
复制标题
注意力缺陷/多动症治疗中给药方案效果的评估方法
DOI：
10.1089/cap.2016.0108
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发表时间：
2017-05-01
影响因子：
1.9
通讯作者：
Nekka, Fahima
中科院分区：
文献类型：
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作者：
Bonnefois, Guillaume;Robaey, Philippe;Nekka, Fahima
目的：以哌醋甲酯为主要药物的兴奋剂是治疗注意缺陷多动障碍的常用药物。然而，对于关心治疗方案在剂量和时间方面适应儿童日常活动的临床医生来说，真正的挑战仍然存在。本研究的目的是通过基于网络的应用来评估特定方案的性能，从而根据特定儿童的需要来优化短效方案。方法：在本文中，考虑到儿童的日常活动，并利用最新的哌酸甲酯的药代动力学知识，我们提出了一种基于药物浓度和活动时间限制的计算方法来确定最合适的剂量方案。为了评估这些方案的效果，提出了基于时间和浓度的治疗指标，以及过山车效应。结果：基于所提出的给药方案评估方法，开发了一个可作为临床医生和患者教育工具的网络界面。将我们的方法确定的最优方案与NIMH联合多部位多模式治疗儿童注意缺陷/多动障碍研究中定义的被广泛接受的方案进行比较，表明当前的做法仍有改进的空间，特别是最后一剂给药，以避免睡眠障碍等副作用。结论：所开发的方法及其相关的网络界面为评估和调整哌醋酸甲酯方案以适应儿童的日常活动提供了一种有效的方法。此外，该方法还可作为进一步实现长效和短效哌醋酸甲酯组合的概念验证。
Objective: Stimulant medications, with methylphenidate as the main agent, are the most prescribed for the treatment of attention-deficit/hyperactivity disorder. Nevertheless, real challenges still remain for clinicians concerned with adaptation of the therapeutic regimens, in terms of doses and timing, to children's daily activities. The aim of this study was to optimize short-acting methylphenidate regimens according to specific children's needs by evaluating the performance of a particular regimen through a web-based application.Methods: In this article, accounting for day-to-day children's activities and using up-to-date pharmacokinetic knowledge of methylphenidate, we propose a computational approach for the identification of the most suitable dosing regimens of immediate-release formulations of methylphenidate based on constraints on drug concentration and time frame of activities, defined through therapeutic boxes. To assess the performance of these regimens, time- and concentration-based therapeutic indicators, as well as a roller coaster effect, are proposed.Results: A web-based interface that can serve as an educational tool for clinicians and patients has been developed based on the proposed approach for the evaluation of dosing regimens. Comparison of those optimal regimens identified by our method with the well-accepted regimens defined in the NIMH Collaborative Multisite Multimodal Treatment study of Children with attention-deficit/hyperactivity disorder indicates that there is still room for improvement in the current practice especially for the last dose administration to avoid side effects such as sleep disturbance.Conclusion: The developed approach and its associated web-based interface provide an efficient way to evaluate and adapt the methylphenidate regimens to children's daily activities. In addition, this approach could be used as proof of concept to further implement combination of short- and long-acting methylphenidate.