Prospective study of serum and ionized magnesium pharmacokinetics in the treatment of children with severe acute asthma.

ABSTRACT

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.