Clinical pharmacokinetics of magnesium sulfate in the treatment of children with severe acute asthma

Purpose: Intravenous (IV) magnesium sulfate (MgSO₄) is used as adjunct therapy to treat acute asthma exacerbations. Despite its clinical use, there is a limited understanding of the disposition of magnesium in children.

Methods: To explore the pharmacokinetics (PK) of IV MgSO₄ in this population, we collected retrospective data from 54 children who received IV MgSO₄ for treatment of an acute asthma exacerbation at Primary Children's Hospital in Salt Lake City, UT. These data were analyzed using population PK modeling techniques in NONMEM® to determine sources of variability affecting the disposition of magnesium, as well as to predict the dose of IV MgSO₄ needed to achieve clinical benefit.

Results: The covariate analysis found that only weight was a significant predictor of magnesium concentrations in children. Estimated model parameters suggested that magnesium exhibits a short serum half-life (2.7 h) in children. The average endogenous magnesium concentration (prior to administration of IV MgSO₄) was estimated to be 21 mg/L. Simulated data suggested that doses between 50 and 75 mg/kg are required to achieve concentration-time profiles within a hypothesized target therapeutic range between 25 and 40 mg/L.

Conclusions: These results provide new insight into the disposition of IV MgSO₄ in children and provide dosing guidelines for future prospective studies of IV MgSO₄ in children with acute asthma.