title: Clinical pharmacokinetics of magnesium sulfate in the treatment of children with severe acute asthma.
abstract: OBJECTIVE
  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 MgSO4in this population, we collected retrospective data from 54 children who received IV MgSO4for 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 MgSO4needed 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 MgSO4in children and provide dosing guidelines for future prospective studies of IV MgSO4in children with acute asthma.
authors.affiliation: Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, 295 Chipeta Way 1S100, Salt Lake City, UT, 84108, USA. Joseph.Rower@hsc.utah.edu.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Rower
authors.affiliation: Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, 295 Chipeta Way 1S100, Salt Lake City, UT, 84108, USA.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, 295 Chipeta Way 1S100, Salt Lake City, UT, 84108, USA.
authors.forename: Tian
authors.initials: T
authors.lastname: Yu
authors.affiliation: Primary Children's Medical Center, Intermountain Healthcare, Salt Lake City, UT, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mundorff
authors.affiliation: Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, 295 Chipeta Way 1S100, Salt Lake City, UT, 84108, USA.
authors.forename: Catherine M T
authors.initials: CM
authors.lastname: Sherwin
authors.affiliation: Primary Children's Medical Center, Intermountain Healthcare, Salt Lake City, UT, USA.|Division of Emergency Medicine, Department of Pediatrics, University of UT, Salt Lake City, UT, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Johnson
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D001249:Asthma / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008278:Magnesium Sulfate / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D012720:Severity of Illness Index
chemical_list: D008278:Magnesium Sulfate
keywords: Acute asthma; Intravenous magnesium sulfate; Population pharmacokinetics; Serum magnesium