Jill Durocher

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

June 4th, 2013
Salinger, D.H., Mundle, S., Regi, A., Bracken, H., Winikoff, B., Vicini, P., Easterling, T.

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

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.