Clinical pharmacokinetic properties of magnesium sulphate in women with pre-eclampsia and eclampsia

Background: The pharmacokinetic basis of magnesium sulphate (MgSO4 ) dosing regimens for eclampsia prophylaxis and treatment is not clearly established.

Objectives: To review available data on clinical pharmacokinetic properties of MgSO4 when used for women with pre-eclampsia and/or eclampsia.

Search strategy: MEDLINE, EMBASE, CINAHL, POPLINE, Global Health Library and reference lists of eligible studies.

Selection criteria: All study types investigating pharmacokinetic properties of MgSO4 in women with pre-eclampsia and/or eclampsia.

Data collection and analysis: Two authors extracted data on basic pharmacokinetic parameters reflecting the different aspects of absorption, bioavailability, distribution and excretion of MgSO4 according to identified dosing regimens.

Main results: Twenty-eight studies investigating pharmacokinetic properties of 17 MgSO4 regimens met our inclusion criteria. Most women (91.5%) in the studies had pre-eclampsia. Baseline serum magnesium concentrations were consistently <1 mmol/l across studies. Intravenous loading dose between 4 and 6 g was associated with a doubling of this baseline concentration half an hour after injection. Maintenance infusion of 1 g/hour consistently produced concentrations well below 2 mmol/l, whereas maintenance infusion at 2 g/hour and the Pritchard intramuscular regimen had higher but inconsistent probability of producing concentrations between 2 and 3 mmol/l. Volume of distribution of magnesium varied (13.65-49.00 l) but the plasma clearance was fairly similar (4.28-5.00 l/hour) across populations.

Conclusion: The profiles of Zuspan and Pritchard regimens indicate that the minimum effective serum magnesium concentration for eclampsia prophylaxis is lower than the generally accepted level. Exposure-response studies to identify effective alternative dosing regimens should target concentrations achievable by these standard regimens.

Tweetable abstract: Minimum effective serum magnesium concentration for eclampsia prophylaxis is lower than the generally accepted therapeutic level.