Rower Joseph E, Johnson Michael D, Zorc Joseph J, Shihabuddin Bashar, Dai Mengtao, Barney Bradley J, Finkelstein Yaron
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA.
Center for Human Toxicology, University of Utah, Salt Lake City, UT, USA.
J Clin Pharmacol. 2025 Jun;65(6):665-674. doi: 10.1002/jcph.6179. Epub 2025 Jan 7.
Pediatric asthma exacerbations represent a significant cause of emergency department use and hospitalizations. Despite available treatment options, many children's exacerbations are refractory to standard therapies and require adjunct treatments. The Intravenous Magnesium: Prompt use for Asthma in Children Treated in the Emergency Department study investigated the pharmacology of intravenous magnesium sulfate (IVMg) in treating pediatric asthma exacerbations. Specifically, the objectives of the study included (1) externally validating a previously published population pharmacokinetic model and (2) linking serum magnesium concentrations with outcomes including asthma severity score (efficacy) and hypotension (safety). Data were obtained from 49 children prospectively treated with IVMg (placebo, 50 or 75 mg/kg) after presenting to the pediatric emergency department with an acute asthma exacerbation. Reductions in Pediatric Respiratory Assessment Measure scores were associated with both total and ionized serum magnesium area under the concentration-time curve (AUC). Despite frequent study-specific blood pressure monitoring, hypotension was uncommon in IVMg-treated participants (n = 2/31), and no concentration dependence was observed. The findings signal that IVMg may be an efficacious and safe option for treating moderate-severe pediatric acute asthma exacerbations in the ED. Importantly, this study is the first to suggest a serum exposure target (total serum magnesium AUC >63.1 mg h/L) reflective of effective IVMg dosing in pediatric acute asthma. While further study in a larger clinical trial is needed to refine and validate this exposure target, these findings support the continued study of IVMg therapy as an adjunct therapeutic option in the setting of pediatric asthma exacerbations.
小儿哮喘急性发作是急诊就诊和住院的重要原因。尽管有可用的治疗方案，但许多儿童的急性发作对标准疗法无效，需要辅助治疗。“急诊科治疗儿童哮喘时静脉注射镁的及时应用”研究调查了静脉注射硫酸镁（IVMg）治疗小儿哮喘急性发作的药理学。具体而言，该研究的目标包括：（1）对外验证先前发表的群体药代动力学模型；（2）将血清镁浓度与包括哮喘严重程度评分（疗效）和低血压（安全性）在内的结果联系起来。数据来自49名因急性哮喘发作到儿科急诊科就诊后接受IVMg（安慰剂、50或75mg/kg）前瞻性治疗的儿童。儿科呼吸评估量表评分的降低与血清总镁和离子化镁浓度-时间曲线下面积（AUC）均相关。尽管频繁进行特定研究的血压监测，但在接受IVMg治疗的参与者中低血压并不常见（n = 2/31），且未观察到浓度依赖性。这些发现表明，IVMg可能是急诊科治疗中重度小儿急性哮喘发作的一种有效且安全的选择。重要的是，本研究首次提出了一个血清暴露目标（血清总镁AUC>63.1mg·h/L），该目标反映了小儿急性哮喘中IVMg有效给药情况。虽然需要在更大规模的临床试验中进一步研究以完善和验证这一暴露目标，但这些发现支持继续研究IVMg疗法作为小儿哮喘急性发作时的辅助治疗选择。
