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Population Pharmacokinetic Modeling to Evaluate Standard Magnesium Sulfate Treatments and Alternative Dosing Regimens for Women With Preeclampsia.

Publication ,  Journal Article
Du, L; Wenning, L; Migoya, E; Xu, Y; Carvalho, B; Brookfield, K; Witjes, H; de Greef, R; Lumbiganon, P; Sangkomkamhang, U; Titapant, V ...
Published in: Journal of clinical pharmacology
March 2019

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.

Duke Scholars

Published In

Journal of clinical pharmacology

DOI

EISSN

1552-4604

ISSN

0091-2700

Publication Date

March 2019

Volume

59

Issue

3

Start / End Page

374 / 385

Related Subject Headings

  • Pregnancy
  • Pre-Eclampsia
  • Pharmacology & Pharmacy
  • Magnesium Sulfate
  • Injections, Intramuscular
  • Infusions, Intravenous
  • Humans
  • Female
  • Adult
  • 3214 Pharmacology and pharmaceutical sciences
 

Citation

APA
Chicago
ICMJE
MLA
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Du, L., Wenning, L., Migoya, E., Xu, Y., Carvalho, B., Brookfield, K., … Oladapo, O. T. (2019). Population Pharmacokinetic Modeling to Evaluate Standard Magnesium Sulfate Treatments and Alternative Dosing Regimens for Women With Preeclampsia. Journal of Clinical Pharmacology, 59(3), 374–385. https://doi.org/10.1002/jcph.1328
Du, Lihong, Larissa Wenning, Elizabeth Migoya, Yan Xu, Brendan Carvalho, Kathleen Brookfield, Han Witjes, et al. “Population Pharmacokinetic Modeling to Evaluate Standard Magnesium Sulfate Treatments and Alternative Dosing Regimens for Women With Preeclampsia.Journal of Clinical Pharmacology 59, no. 3 (March 2019): 374–85. https://doi.org/10.1002/jcph.1328.
Du L, Wenning L, Migoya E, Xu Y, Carvalho B, Brookfield K, et al. Population Pharmacokinetic Modeling to Evaluate Standard Magnesium Sulfate Treatments and Alternative Dosing Regimens for Women With Preeclampsia. Journal of clinical pharmacology. 2019 Mar;59(3):374–85.
Du, Lihong, et al. “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, Mar. 2019, pp. 374–85. Epmc, doi:10.1002/jcph.1328.
Du L, Wenning L, Migoya E, Xu Y, Carvalho B, Brookfield K, Witjes H, de Greef R, Lumbiganon P, Sangkomkamhang U, Titapant V, Duley L, Long Q, Oladapo OT. Population Pharmacokinetic Modeling to Evaluate Standard Magnesium Sulfate Treatments and Alternative Dosing Regimens for Women With Preeclampsia. Journal of clinical pharmacology. 2019 Mar;59(3):374–385.

Published In

Journal of clinical pharmacology

DOI

EISSN

1552-4604

ISSN

0091-2700

Publication Date

March 2019

Volume

59

Issue

3

Start / End Page

374 / 385

Related Subject Headings

  • Pregnancy
  • Pre-Eclampsia
  • Pharmacology & Pharmacy
  • Magnesium Sulfate
  • Injections, Intramuscular
  • Infusions, Intravenous
  • Humans
  • Female
  • Adult
  • 3214 Pharmacology and pharmaceutical sciences