Magnesium sulphate for prevention of eclampsia: are intramuscular and intravenous regimens equivalent? A population pharmacokinetic study

BJOG. 2013 Jun;120(7):894-900. doi: 10.1111/1471-0528.12222. Epub 2013 Mar 26.

Abstract

Objective: To compare magnesium sulphate concentrations achieved by intramuscular and intravenous regimens used for the prevention of eclampsia.

Setting: Low-resource obstetric hospitals in Nagpur and Vellore, India.

Population: Pregnant women at risk for eclampsia due to hypertensive disease.

Methods: A pharmacokinetic study was performed as part of a randomised trial that enrolled 300 women comparing intramuscular and intravenous maintenance regimens of magnesium dosing. Data from 258 enrolled women were analysed in the pharmacokinetic study. A single sample was drawn per woman with the expectation of using samples in a pooled data analysis.

Main outcome measures: Pharmacokinetic parameters of magnesium distribution and clearance.

Results: Magnesium clearance was estimated to be 48.1 dl/hour, volume of distribution to be 156 dl and intramuscular bioavailability to be 86.2%. The intramuscular regimen produced higher initial serum concentrations, consistent with a substantially larger loading dose. At steady state, magnesium concentrations in the intramuscular and intravenous groups were comparable. With either regimen, a substantial number of women would be expected to have serum concentrations lower than those generally held to be therapeutic.

Conclusions: Clinical implications were that a larger loading dose for the intravenous regimen should be considered; where feasible, individualised dosing of magnesium sulphate would reduce the variability in serum concentrations and might result in more women with clinically effective magnesium concentrations; and lower dose magnesium sulphate regimens should be considered with caution.

Trial registration: ClinicalTrials.gov NCT00666133.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / pharmacokinetics*
  • Anticonvulsants / therapeutic use
  • Biological Availability
  • Drug Administration Schedule
  • Eclampsia / prevention & control*
  • Female
  • Humans
  • Infusions, Intravenous
  • Injections, Intramuscular
  • Magnesium Sulfate / administration & dosage
  • Magnesium Sulfate / pharmacokinetics*
  • Magnesium Sulfate / therapeutic use
  • Metabolic Clearance Rate
  • Pre-Eclampsia / drug therapy*
  • Pregnancy
  • Young Adult

Substances

  • Anticonvulsants
  • Magnesium Sulfate

Associated data

  • ClinicalTrials.gov/NCT00666133