Prospective study of serum and ionized magnesium pharmacokinetics in the treatment of children with severe acute asthma
Intravenous (IV) magnesium sulfate (MgSO4) 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 MgSO4 administration in children with severe acute asthma.
Thirty-two children receiving 50 mg/kg IV MgSO4 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 MgSO4 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 MgSO4 administration in children. A single bolus infusion of IV MgSO4 was safe in this small sample of children receiving it for acute asthma.
KeywordsIntravenous magnesium sulfate Serum magnesium Ionized magnesium Population pharmacokinetics Acute asthma
We would like to acknowledge the patients who participated in the study, as well as the University of California, Davis, Clinical Chemistry Section for performing the analysis of magnesium concentrations.
Contribution of authors
SB facilitated the IRB application and participant recruitment for the prospective clinical study, provided clinical care to the study participants, and was involved in the preparation of the manuscript. KJ facilitated the IRB application and participant recruitment for the prospective clinical study. KL and NKT did the laboratory analysis of the collected samples. TF and JW contributed to data cleaning, formatting, and analysis. CMS and DN were involved with study concept/design, and DN contributed to the clinical care of study participants. MDJ was involved with study concept/design, provided clinical care to study participants, and participated in preparing the manuscript. JER was involved with study concept/design, completed the described PK analysis, and wrote the manuscript. All authors participated in editing the manuscript prior to submission.
Funding for this study was provided by the Primary Children’s Hospital Foundation, as well as the Division of Pediatric Clinical Pharmacology and the Division of Pediatric Emergency Medicine at the University of Utah.
Compliance with ethical standards
Study approval was granted by the University of Utah, Intermountain Health, and Primary Children’s Hospital Institutional Review Board.
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