{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T07:12:39Z","timestamp":1763017959094},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T00:00:00Z","timestamp":1542067200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004423","name":"World Health Organization","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004423","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Magnesium sulfate is the standard therapy for prevention and treatment of eclampsia. Two\u00a0standard dosing regimens require either continuous intravenous infusion or frequent, large\u2010volume 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\u2010compartment population pharmacokinetic (PK) model was developed to characterize serial PK data from 92\u00a0pregnant 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\u00a0standard 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\u2010g intramuscular loading doses with maintenance doses of 8 g every 6\u00a0hours 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.<\/jats:p>","DOI":"10.1002\/jcph.1328","type":"journal-article","created":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T15:55:08Z","timestamp":1542124508000},"page":"374-385","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Population Pharmacokinetic Modeling to Evaluate Standard Magnesium Sulfate Treatments and Alternative Dosing Regimens for Women With Preeclampsia"],"prefix":"10.1002","volume":"59","author":[{"given":"Lihong","family":"Du","sequence":"first","affiliation":[{"name":"PPDM, QP2, Merck &amp; Co., Inc.  West Point PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larissa","family":"Wenning","sequence":"additional","affiliation":[{"name":"PPDM, QP2, Merck &amp; Co., Inc.  West Point PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Migoya","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Myovant Sciences, Inc.  Brisbane CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"Global Clinical Pharmacology Janssen Research &amp; Development, LLC  Spring House PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brendan","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine Stanford University School of Medicine  Stanford CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Brookfield","sequence":"additional","affiliation":[{"name":"Oregon Health &amp; Science University  Portland OR USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Witjes","sequence":"additional","affiliation":[{"name":"Certara Strategic Consulting  Oss Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rik","family":"de Greef","sequence":"additional","affiliation":[{"name":"Certara Strategic Consulting  Oss Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pisake","family":"Lumbiganon","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine Khon Kaen University  Khon Kaen Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ussanee","family":"Sangkomkamhang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine Khon Kaen University  Khon Kaen Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vitaya","family":"Titapant","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Siriraj Hospital Mahidol University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lelia","family":"Duley","sequence":"additional","affiliation":[{"name":"Nottingham Clinical Trials Unit University of Nottingham  Nottingham United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Long","sequence":"additional","affiliation":[{"name":"UNDP\/UNFPA\/UNICEF\/WHO\/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research World Health Organization  Geneva Switzerland"},{"name":"Global Health Research Center Duke Kunshan University  Jiangsu Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olufemi T.","family":"Oladapo","sequence":"additional","affiliation":[{"name":"UNDP\/UNFPA\/UNICEF\/WHO\/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research World Health Organization  Geneva Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08778-0"},{"issue":"1","key":"e_1_2_10_3_1","first-page":"1","article-title":"A brief overview of preeclampsia","volume":"6","author":"Al\u2010Jameil N","year":"2014","journal-title":"J Clin Med Res"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/586578"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2013.08.019"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(78)90816-5"},{"key":"e_1_2_10_7_1","first-page":"CD000025","article-title":"Magnesium sulphate and other anticonvulsants for women with pre\u2010eclampsia","volume":"11","author":"Duley L","year":"2010","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_10_8_1","unstructured":"Program for Appropriate Technology in Health (PATH).Delivery of Magnesium Sulfate. 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