Becker Sarah M, Job Kathleen M, Lima Kelly, Forbes Ty J, Wagstaff Jadon, Tran Nam K, Sherwin Catherine M, Nelson Douglas S, Johnson Michael D, Rower Joseph E
Primary Children's Hospital, Intermountain Healthcare, Salt Lake City, UT, USA.
Division of Pediatric Emergency Medicine, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
Eur J Clin Pharmacol. 2019 Jan;75(1):59-66. doi: 10.1007/s00228-018-2557-7. Epub 2018 Sep 26.
Intravenous (IV) magnesium sulfate (MgSO) is clinically useful as adjunct therapy in treating acute asthma exacerbations. Despite its clinical utility, the disposition of magnesium in children is poorly described. The purpose of this study is to describe the pharmacokinetics (PK) of ionized and total serum magnesium following IV MgSO administration in children with severe acute asthma.
Thirty-two children receiving 50 mg/kg IV MgSO for acute asthma exacerbations at Primary Children's Hospital in Salt Lake City, UT, were prospectively enrolled in the study. Blood samples were collected before, as well as 30 min and 2 h after each child's IV MgSO dose, and used to determine total serum and ionized magnesium concentrations. The collected data were analyzed using population PK techniques using NONMEM® software.
Total serum magnesium concentrations were used to externally validate our previously published model constructed with retrospective data (median prediction error 10.3%, median absolute prediction error 18.1%). The mean (%CV) observed endogenous ionized magnesium concentration was calculated to be 6.0 mg/L (12%), approximately one third of the same value for endogenous total serum magnesium (17.6 mg/L (22%)) in this dataset. Weight was a significant predictor of both clearance and volume in a population PK model describing ionized magnesium concentrations. No adverse events were observed in this pediatric cohort.
This prospective study supports and extends our previous PK analysis of total serum magnesium concentrations. Ionized and total serum magnesium followed similar PK profiles following IV MgSO administration in children. A single bolus infusion of IV MgSO was safe in this small sample of children receiving it for acute asthma.
静脉注射硫酸镁在治疗急性哮喘发作时作为辅助疗法具有临床应用价值。尽管其具有临床实用性，但镁在儿童体内的处置情况却鲜有描述。本研究的目的是描述重度急性哮喘患儿静脉注射硫酸镁后血清离子镁和总镁的药代动力学（PK）。
前瞻性纳入了32名在犹他州盐湖城 Primary Children's Hospital因急性哮喘发作接受50mg/kg静脉注射硫酸镁的儿童。在每个儿童静脉注射硫酸镁剂量前、给药后30分钟和2小时采集血样，用于测定血清总镁和离子镁浓度。使用NONMEM®软件，采用群体PK技术对收集的数据进行分析。
血清总镁浓度用于外部验证我们之前利用回顾性数据构建的模型（中位预测误差10.3%，中位绝对预测误差18.1%）。在该数据集中，观察到的内源性离子镁浓度的平均值（%CV）计算为6.0mg/L（12%），约为内源性血清总镁相同值（17.6mg/L（22%））的三分之一。在描述离子镁浓度的群体PK模型中，体重是清除率和容积的显著预测因子。在这个儿科队列中未观察到不良事件。
这项前瞻性研究支持并扩展了我们之前对血清总镁浓度的PK分析。儿童静脉注射硫酸镁后，离子镁和血清总镁的PK曲线相似。在这个因急性哮喘接受静脉注射硫酸镁的小样本儿童中，单次大剂量输注是安全的。
