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伊维菌素剂量策略在儿童和成人中实现等效暴露覆盖。

Ivermectin Dosing Strategy to Achieve Equivalent Exposure Coverage in Children and Adults.

机构信息

Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.

University of Basel, Basel, Switzerland.

出版信息

Clin Pharmacol Ther. 2019 Sep;106(3):661-667. doi: 10.1002/cpt.1456. Epub 2019 May 25.

Abstract

Ivermectin is a commonly used broad-spectrum antiparasitic drug, yet doses that produce consistent exposure coverage across age have not been characterized, and no data are available in children weighing < 15 kg. First, a population pharmacokinetic model is developed based on data from 200 children and 11 adults, treated with 100-600 μg/kg ivermectin. Second, model-based simulations are performed to identify a dosing strategy that achieves equivalent exposure coverage in children and adults. Median (90% confidence interval) clearance of 0.346 (0.12-0.73) L/hour/kg in pre-school-aged (2-5 years) children is similar to 0.352 (0.17-0.69) L/hour/kg in school-aged (6-12 years) children but higher than in adults (0.199 (0.10-0.31) L/hour/kg), resulting in significantly lower exposure in children following a 200 μg/kg dose. Simulations indicate that a dose increase to 300 and 250 μg/kg in children aged 2-5 and 6-12 years, respectively, will achieve equivalent ivermectin exposure coverage in children and adults.

摘要

伊维菌素是一种常用的广谱抗寄生虫药物,但尚未确定能在各年龄段产生一致暴露覆盖的剂量,并且在体重<15kg 的儿童中也没有可用数据。首先,根据 200 名儿童和 11 名成人接受 100-600μg/kg 伊维菌素治疗的数据,建立了群体药代动力学模型。其次,通过模型模拟确定了一种给药策略,该策略可使儿童和成人获得等效的暴露覆盖。2-5 岁学龄前儿童(2-5 岁)的清除率中位数(90%置信区间)为 0.346(0.12-0.73)L/h/kg,与 6-12 岁学龄儿童(6-12 岁)的 0.352(0.17-0.69)L/h/kg 相似,但高于成人(0.199(0.10-0.31)L/h/kg),导致 200μg/kg 剂量后儿童的暴露量明显降低。模拟表明,分别将 2-5 岁和 6-12 岁儿童的剂量增加至 300μg/kg 和 250μg/kg,可使儿童和成人获得等效的伊维菌素暴露覆盖。

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