Optimal designs for population pharmacokinetic studies of oral artesunate in patients with uncomplicated falciparum malaria.
Optimal designs for population pharmacokinetic studies of oral artesunate in patients with uncomplicated falciparum malaria.
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DOI：
10.1186/1475-2875-10-181
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发表时间：
2011-07-01
期刊：
影响因子：
3
通讯作者：
Simpson JA
中科院分区：
文献类型：
--
作者：
Jamsen KM;Duffull SB;Tarning J;Lindegardh N;White NJ;Simpson JA
目前，抗疟疾药物的群体药代动力学（PK）研究主要是根据从患者身上采集血液样本的后勤和伦理限制来设计的，并且没有正式考虑与数据相适应的统计模型。这可能导致对目标PK参数的不精确估计，和/或设计不足以估计所有参数。优化设计的方法已经开发，以确定血液采样时间表，将产生精确的参数估计在采样研究人群的实际限制。本研究采用优化设计方法确定了双氢青蒿素（口服青蒿琥酯的主要生物活性代谢物）未来典型种群PK研究的抽样设计。使用免费软件推导出最佳设计，并基于对数据或文献分析的适当结构PK模型和发送给活跃疟疾研究人员的问卷中确定的关键抽样约束（每个患者3-4个样本，样本之间至少15分钟）。然后通过仿真估计对得到的最优设计进行评价。得出的最佳采样窗口为17 ~ 29分钟、30 ~ 57分钟、2.5 ~ 3.7小时和5.8 ~ 6.6小时；16至29分钟，31分钟至1小时，2.0至3.4小时，5.5至6.6小时，非怀孕成人和儿童设计35至59分钟，1.2至3.4小时，3.4至4.9小时，6.0至8.0小时，孕妇设计。通过优化设计，得到了可接受的PK参数精度。本文提出的采样设计稳健且高效，在未来口服青蒿琥酯的PK研究中应予以考虑，因为只有三到四个血液样本可以收集。
Currently, population pharmacokinetic (PK) studies of anti-malarial drugs are designed primarily by the logistical and ethical constraints of taking blood samples from patients, and the statistical models that are fitted to the data are not formally considered. This could lead to imprecise estimates of the target PK parameters, and/or designs insufficient to estimate all of the parameters. Optimal design methodology has been developed to determine blood sampling schedules that will yield precise parameter estimates within the practical constraints of sampling the study populations. In this work optimal design methods were used to determine sampling designs for typical future population PK studies of dihydroartemisinin, the principal biologically active metabolite of oral artesunate. Optimal designs were derived using freely available software and were based on appropriate structural PK models from an analysis of data or the literature and key sampling constraints identified in a questionnaire sent to active malaria researchers (3-4 samples per patient, at least 15 minutes between samples). The derived optimal designs were then evaluated via simulation-estimation. The derived optimal sampling windows were 17 to 29 minutes, 30 to 57 minutes, 2.5 to 3.7 hours and 5.8 to 6.6 hours for non-pregnant adults; 16 to 29 minutes, 31 minutes to 1 hour, 2.0 to 3.4 hours and 5.5 to 6.6 hours for designs with non-pregnant adults and children and 35 to 59 minutes, 1.2 to 3.4 hours, 3.4 to 4.9 hours and 6.0 to 8.0 hours for pregnant women. The optimal designs resulted in acceptable precision of the PK parameters. The proposed sampling designs in this paper are robust and efficient and should be considered in future PK studies of oral artesunate where only three or four blood samples can be collected.
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影响因子：
6.7
作者：
Barnes, Karen I.;Little, Francesca;White, Nicholas J.
通讯作者：
White, Nicholas J.
DOI：
10.1007/s10928-005-0026-2
发表时间：
2005-08-01
影响因子：
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作者：
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通讯作者：
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影响因子：
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通讯作者：
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作者：
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通讯作者：
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影响因子：
3.9
作者：
Ilett, KF;Ethell, BT;Edwards, G
通讯作者：
Edwards, G