Publication: Population Pharmacokinetic Modeling to Evaluate Standard Magnesium Sulfate Treatments and Alternative Dosing Regimens for Women With Preeclampsia
Issued Date
2019-03-01
Resource Type
ISSN
15524604
00912700
00912700
Other identifier(s)
2-s2.0-85056451786
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Clinical Pharmacology. Vol.59, No.3 (2019), 374-385
Suggested Citation
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 Population Pharmacokinetic Modeling to Evaluate Standard Magnesium Sulfate Treatments and Alternative Dosing Regimens for Women With Preeclampsia. Journal of Clinical Pharmacology. Vol.59, No.3 (2019), 374-385. doi:10.1002/jcph.1328 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/51843
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Population Pharmacokinetic Modeling to Evaluate Standard Magnesium Sulfate Treatments and Alternative Dosing Regimens for Women With Preeclampsia
Other Contributor(s)
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
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
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.