Joseph E Rower1, Xiaoxi Liu2, Tian Yu2, Michael Mundorff3, Catherine M T Sherwin2, Michael D Johnson3,4. 1. 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. 2. Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, 295 Chipeta Way 1S100, Salt Lake City, UT, 84108, USA. 3. Primary Children's Medical Center, Intermountain Healthcare, Salt Lake City, UT, USA. 4. Division of Emergency Medicine, Department of Pediatrics, University of UT, Salt Lake City, UT, USA.
Abstract
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.
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.
Entities:
Keywords:
Acute asthma; Intravenous magnesium sulfate; Population pharmacokinetics; Serum magnesium
Authors: Suzanne Schuh; Stephen B Freedman; Roger Zemek; Amy C Plint; David W Johnson; Francine Ducharme; Jocelyn Gravel; Graham Thompson; Sarah Curtis; Derek Stephens; Allan L Coates; Karen J Black; Darcy Beer; Judy Sweeney; Maggie Rumantir; Yaron Finkelstein Journal: JAMA Netw Open Date: 2021-07-01