Population pharmacokinetics and pharmacodynamics of piperaquine in children with uncomplicated falciparum malaria.
Population pharmacokinetics and pharmacodynamics of piperaquine in children with uncomplicated falciparum malaria.
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DOI：
10.1038/clpt.2011.254
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发表时间：
2012-03
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
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作者：
双氢青蒿素-哌喹越来越多地用作治疗疟疾的一线青蒿素联合疗法。本研究的目的是描述哌喹在布基纳法索 236 名患有单纯性恶性疟疾的儿童中的药代动力学和药效学特性。他们接受了基于标准体重的为期 3 天的口服固定剂量双氢青蒿素-哌喹疗法。使用非线性混合效应模型来表征毛细血管血浆浓度-时间曲线。通过二隔室吸收模型和三隔室分布模型准确地描述了哌喹的群体药代动力学。体重是影响清除率和体积参数的显着协变量。单独预测的第 7 天哌喹毛细血管血浆浓度是治疗后疟疾感染复发的重要预测因子 (P < 0.0001)。幼儿（2-5岁）接受的体重标准化剂量显着高于年龄较大的儿童（P = 0.025），但第7天哌喹浓度（P = 0.024）和总哌喹暴露量（P = 0.021）显着较低，这表明应评估幼儿增加剂量方案。
Dihydroartemisinin-piperaquine is being increasingly used as a first-line artemisinin combination treatment for malaria. The aim of this study was to describe the pharmacokinetic and pharmacodynamic properties of piperaquine in 236 children with uncomplicated falciparum malaria in Burkina Faso. They received a standard body weight–based oral 3-day fixed-dose dihydroartemisinin-piperaquine regimen. Capillary plasma concentration–time profiles were characterized using nonlinear mixed-effects modeling. The population pharmacokinetics of piperaquine were described accurately by a two-transit-compartment absorption model and a three-compartment distribution model. Body weight was a significant covariate affecting clearance and volume parameters. The individually predicted day 7 capillary plasma concentration of piperaquine was an important predictor (P < 0.0001) of recurrent malaria infection after treatment. young children (2–5 years of age) received a significantly higher body weight-normalized dose than older children (P = 0.025) but had significantly lower day 7 piperaquine concentrations (P = 0.024) and total piperaquine exposures (P = 0.021), suggesting that an increased dose regimen for young children should be evaluated.
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DOI：
10.1093/cid/ciq249
发表时间：
2011-03-01
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Douglas NM;Nosten F;Ashley EA;Phaiphun L;van Vugt M;Singhasivanon P;White NJ;Price RN
通讯作者：
Price RN
影响因子：
4.9
作者：
Tarning, J.;Ashley, E. A.;White, N. J.
通讯作者：
White, N. J.
影响因子：
4.9
作者：
Price, R. N.;Hasugian, A. R.;Tjitra, E.
通讯作者：
Tjitra, E.
影响因子：
6.4
作者：
Ashley, EA;Krudsood, S;White, NJ
通讯作者：
White, NJ
影响因子：
6.7
作者：
Barnes, Karen I.;Little, Francesca;White, Nicholas J.
通讯作者：
White, Nicholas J.