Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Epicentre, Paris, France.
Clin Pharmacol Ther. 2019 Dec;106(6):1299-1309. doi: 10.1002/cpt.1531. Epub 2019 Jul 23.
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.
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，并且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，他们接受双氢青蒿素哌喹（ART）每日两次治疗 3 天。卢美酚的毛细血浆浓度可以通过两个转运-吸收隔室，随后是两个分布隔室来很好地描述。根据比例缩放的体重和酶成熟效应纳入 PK 模型。中上臂围与卢美酚的吸收减少相关（每减少 1 厘米，吸收减少 25.4%）。复发性疟疾发作（即再感染）的风险通过时间到事件的间隔censored 模型进行描述，其中卢美酚的效应采用 sigmoid 最大效应模型进行描述。与营养良好的儿童相比，SAM 儿童存在卢美酚暴露不足和疟疾再感染风险增加的情况。应该考虑针对营养不良儿童的优化治疗方案进行研究。
