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

  • BJOG. 2016 Feb;123(3):356-66. doi: 10.1111/1471-0528.13753.
B O Okusanya  1 ,  O T Oladapo  2 ,  Q Long  2 ,  P Lumbiganon  3 ,  G Carroli  4 ,  Z Qureshi  5 ,  L Duley  6 ,  J P Souza  7 ,  A M Gülmezoglu  2
Affiliations
  • 1. Experimental and Maternal Medicine (EMM) Unit, Department of Obstetrics and Gynaecology, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria.
  • 2. 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.
  • 3. Department of Obstetrics and Gynaecology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
  • 4. Centro Rosarino de Estudios Perinatales, Rosario, Argentina.
  • 5. Department of Obstetrics and Gynaecology, School of Medicine, College of Health Sciences, University of Nairobi, Nairobi, Kenya.
  • 6. Nottingham Clinical Trials Unit, Queens Medical Centre, Nottingham, UK.
  • 7. Department of Social Medicine, Ribeirao Preto School of Medicine, University of Sao Paulo, Ribeirao Preto, São Paulo, Brazil.
PMID: 26599617 DOI: 10.1111/1471-0528.13753
Abstract

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.

Keywords
Eclampsia; magnesium sulphate; pharmacokinetics; pre-eclampsia; serum magnesium.
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