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.
['Rower|Joseph E|JE|', 'Liu|Xiaoxi|X|', 'Yu|Tian|T|', 'Mundorff|Michael|M|', 'Sherwin|Catherine M T|CM|', 'Johnson|Michael D|MD|']
D000208:Acute Disease D000293:Adolescent D001249:Asthma D002648:Child D002675:Child, Preschool D005260:Female D006801:Humans D008278:Magnesium Sulfate D008297:Male D012720:Severity of Illness Index
Acute asthma Intravenous magnesium sulfate Population pharmacokinetics Serum magnesium