Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.
University of Basel, Basel, Switzerland.
Clin Pharmacol Ther. 2019 Sep;106(3):661-667. doi: 10.1002/cpt.1456. Epub 2019 May 25.
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.
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。