Severe Acute Malnutrition Results in Lower Lumefantrine Exposure in Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria
Severe Acute Malnutrition Results in Lower Lumefantrine Exposure in Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria
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DOI：
10.1002/cpt.1531
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发表时间：
2019-07-23
影响因子：
6.7
通讯作者：
Tarning, Joel
中科院分区：
文献类型：
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作者：
Chotsiri, Palang;Denoeud-Ndam, Lise;Tarning, Joel
据报道，严重急性营养不良（SAM）与撒哈拉以南非洲儿童疟疾发病率增加有关，并可能影响抗疟药物的药理学。这项群体药代动力学 (PK)-药效学研究纳入了 131 名 SAM 儿童和 266 名非 SAM 儿童，每天两次服用蒿甲醚-本芴醇，持续 3 天。苯芴醇毛细血管血浆浓度通过两个转运吸收室和随后的两个分配室充分描述。 PK 模型中包括异速生长体重和酶促成熟效应。中上臂围与本芴醇吸收减少相关（每减少 1 厘米，吸收减少 25.4%）。疟疾复发（即再次感染）的风险通过间隔删失事件时间模型和描述本芴醇作用的 S 形最大效应模型来表征。与营养良好的儿童相比，SAM 儿童面临苯芴醇暴露不足的风险，并且疟疾再次感染的风险增加。应考虑研究优化营养不良儿童疟疾治疗方案。
Severe acute malnutrition (SAM) has been reported to be associated with increased malaria morbidity in Sub-Saharan African children and may affect the pharmacology of antimalarial drugs. This population pharmacokinetic (PK)-pharmacodynamic study included 131 SAM and 266 non-SAM children administered artemether-lumefantrine twice daily for 3 days. Lumefantrine capillary plasma concentrations were adequately described by two transit-absorption compartments followed by two distribution compartments. Allometrically scaled body weight and an enzymatic maturation effect were included in the PK model. Mid-upper arm circumference was associated with decreased absorption of lumefantrine (25.4% decreased absorption per 1 cm reduction). Risk of recurrent malaria episodes (i.e., reinfection) were characterized by an interval-censored time-to-event model with a sigmoid maximum-effect model describing the effect of lumefantrine. SAM children were at risk of underexposure to lumefantrine and an increased risk of malaria reinfection compared with well-nourished children. Research on optimized regimens should be considered for malaria treatment in malnourished children.