Journal
JOURNAL OF CLINICAL PHARMACOLOGY
Volume 59, Issue 3, Pages 374-385Publisher
WILEY
DOI: 10.1002/jcph.1328
Keywords
alternative dosing regimens; magnesium sulfate; modeling and simulation; population pharmacokinetics; preeclampsia
Categories
Funding
- Merck for Mothers (a philanthropic initiative of Merck & Co., Inc., Kenilworth, N.J., USA)
- UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland
- MRC [G116/98] Funding Source: UKRI
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Magnesium sulfate is the standard therapy for prevention and treatment of eclampsia. Twostandard 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 92pregnant 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 2standard 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 6hours 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.
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