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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/51843
Title: Population Pharmacokinetic Modeling to Evaluate Standard Magnesium Sulfate Treatments and Alternative Dosing Regimens for Women With Preeclampsia
Authors: Lihong Du
Larissa Wenning
Elizabeth Migoya
Yan Xu
Brendan Carvalho
Kathleen Brookfield
Han Witjes
Rik de Greef
Pisake Lumbiganon
Ussanee Sangkomkamhang
Vitaya Titapant
Lelia Duley
Qian Long
Olufemi T. Oladapo
Duke Kunshan University
Janssen Research & Development
Stanford University School of Medicine
Organisation Mondiale de la Santé
Faculty of Medicine, Khon Kaen University
Oregon Health and Science University
University of Nottingham
Faculty of Medicine, Siriraj Hospital, Mahidol University
Merck & Co., Inc.
Myovant Sciences, Inc.
Certara Strategic Consulting
Keywords: Medicine
Issue Date: 1-Mar-2019
Citation: Journal of Clinical Pharmacology. Vol.59, No.3 (2019), 374-385
Abstract: © 2018, The American College of Clinical Pharmacology Magnesium sulfate is the standard therapy for prevention and treatment of eclampsia. Two standard dosing regimens require either continuous intravenous infusion or frequent, large-volume intramuscular injections, which may preclude patients from receiving optimal care. This project sought to identify alternative, potentially more convenient, but similarly effective dosing regimens that could be used in restrictive clinical settings. A 2-compartment population pharmacokinetic (PK) model was developed to characterize serial PK data from 92 pregnant women with preeclampsia who received magnesium sulfate. Body weight and serum creatinine concentration had a significant impact on magnesium PK. The final PK model was used to simulate magnesium concentration profiles for the 2 standard regimens and several simplified alternative dosing regimens. The simulations suggest that intravenous regimens with loading doses of 8 g over 60 minutes followed by 2 g/h for 10 hours and 12 g over 120 minutes followed by 2 g/h for 8 hours (same total dose as the standard intravenous regimen but shorter treatment duration) would result in magnesium concentrations below the toxic range. For the intramuscular regimens, higher maintenance doses given less frequently (4 g intravenously + 10-g intramuscular loading doses with maintenance doses of 8 g every 6 hours or 10 g every 8 hours for 24 hours) or removal of the intravenous loading dose (eg, 10 g intramusculary every 8 hours for 24 hours) may be reasonable alternatives. In addition, individualized dose adjustments based on body weight and serum creatinine were proposed for the standard regimens.
URI: http://repository.li.mahidol.ac.th/dspace/handle/123456789/51843
metadata.dc.identifier.url: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85056451786&origin=inward
ISSN: 15524604
00912700
Appears in Collections:Scopus 2019

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