Malaria PK/PD and the Role Pharmacometrics Can Play in the Global Health Arena: Malaria Treatment Regimens for Vulnerable Populations.
Malaria PK/PD and the Role Pharmacometrics Can Play in the Global Health Arena: Malaria Treatment Regimens for Vulnerable Populations.
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DOI：
10.1002/cpt.2238
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发表时间：
2021-10
影响因子：
6.7
通讯作者：
Savic RM
中科院分区：
文献类型：
--
作者：
Hughes E;Wallender E;Mohamed Ali A;Jagannathan P;Savic RM
疟疾是一种传染病，对儿童和孕妇的影响尤为严重。这些易受伤害的人群经常被排除在临床试验之外，导致基于非怀孕成人人群的治疗方案的“一应俱全”。药代动力学/药效学（PK/PD）模型可用于优化剂量选择，因为它们定义了药物暴露-反应关系。此外，这些模型能够识别导致预期PK/PD变化的患者特征，并通过模拟可以建议改变剂量以补偿差异。在这篇综述中，我们研究了PK/PD模型如何应用于优化幼儿的抗疟疾剂量建议，包括营养不良儿童、孕妇和接受艾滋病治疗等伴随治疗的个体。疟疾领域在利用PK/PD模型作为基础更新治疗指南和提出下一代给药方案以供临床试验研究方面取得了巨大成功。我们建议疟疾领域如何通过进一步将PK数据整合到临床研究中，并在PK/PD模型中包括耐药性和宿主免疫数据，继续使用建模来改进治疗。最后，我们建议其他疾病领域可以通过实施三个关键原则，在应用药物计量学来改善结果方面取得类似的成功。
Malaria is an infectious disease which disproportionately effects children and pregnant women. These vulnerable populations are often excluded from clinical trials resulting in one‐size‐fits‐all treatment regimens based on those established for a nonpregnant adult population. Pharmacokinetic/pharmacodynamic (PK/PD) models can be used to optimize dose selection as they define the drug exposure‐response relationship. Additionally, these models are able to identify patient characteristics that cause alterations in the expected PK/PD profiles and through simulations can recommend changes to dosing which compensate for the differences. In this review, we examine how PK/PD models have been applied to optimize antimalarial dosing recommendations for young children, including those who are malnourished, pregnant women, and individuals receiving concomitant therapies such as those for HIV treatment. The malaria field has had great success in utilizing PK/PD models as a foundation to update treatment guidelines and propose the next generation of dosing regimens to investigate in clinical trials. We propose how the malaria field can continue to use modeling to improve therapies by further integrating PK data into clinical studies and including data on drug resistance and host immunity in PK/PD models. Finally, we suggest that other disease areas can achieve similar success in applying pharmacometrics to improve outcomes by implementing three key principals.
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DOI：
10.1093/jac/dks207
发表时间：
2012-09
期刊：
The Journal of antimicrobial chemotherapy
影响因子：
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作者：
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DOI：
10.1124/jpet.106.112136
发表时间：
2007-01-01
影响因子：
3.5
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
Ezzet, F;van Vugt, M;White, NJ
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White, NJ