Clinical Pharmacokinetics

, Volume 38, Issue 4, pp 305–314 | Cite as

Magnesium Sulfate in Eclampsia and Pre-Eclampsia

Pharmacokinetic Principles
  • Jian F. Lu
  • Charles H. Nightingale
Review Article Drug Disposition


Magnesium sulfate (MgSC4) is the agent most commonly used for treatment of eclampsia and prophylaxis of eclampsia in patients with severe pre-eclampsia. It is usually given by either the intramuscular or intravenous routes. The intramuscular regimen is most commonly a 4g intravenous loading dose, immediately followed by 10g intramuscularly and then by 5g intramuscularly every 4 hours in alternating buttocks. The intravenous regimen is given as a 4g dose, followed by a maintenance infusion of 1 to 2 g/h by controlled infusion pump.

After administration, about 40% of plasma magnesium is protein bound. The unbound magnesium ion diffuses into the extravascular-extracellular space, into bone, and across the placenta and fetal membranes and into the fetus and amniotic fluid. In pregnant women, apparent volumes of distribution usually reach constant values between the third and fourth hours after administration, and range from 0.250 to 0.442 L/kg. Magnesium is almost exclusively excreted in the urine, with 90% of the dose excreted during the first 24 hours after an intravenous infusion of MgSO4. The pharmacokinetic profile of MgSO4 after intravenous administration can be described by a 2-compartment model with a rapid distribution (α) phase, followed by a relative slow β phase of elimination.

The clinical effect and toxicity of MgSO4 can be linked to its concentration in plasma. A concentration of 1.8 to 3.0 mmol/L has been suggested for treatment of eclamptic convulsions. The actual magnesium dose and concentration needed for prophylaxis has never been estimated. Maternal toxicity is rare when MgSO4is carefully administered and monitored. The first warning of impending toxicity in the mother is loss of the patellar reflex at plasma concentrations between 3.5 and 5 mmol/L. Respiratory paralysis occurs at 5 to 6.5 mmol/L. Cardiac conduction is altered at greater than 7.5 mmol/L, and cardiac arrest can be expected when concentrations of magnesium exceed 12.5 mmol/L. Careful attention to the monitoring guidelines can prevent toxicity. Deep tendon reflexes, respiratory rate, urine output and serum concentrations are the most commonly followed variables.

In this review, we will outline the currently available knowledge of the pharmacokinetics of MgSO4 and its clinical usage for women with pre-eclampsia and eclampsia.


Magnesium Concentration Eclampsia Deep Tendon Reflex Maintenance Infusion Seizure Prophylaxis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors would like to thank Xiaomei Cao and Jinqiu Xu for their assistance in preparing the manuscript, and Dr Cyprian O. Onyeji for his review.


  1. 1.
    Pritchard JA. Management of pre-eclampsia and eclampsia. Kidney Int 1980; 18: 259–66PubMedCrossRefGoogle Scholar
  2. 2.
    Saftlas AF, Olson DR, Franks AL, et al. Epidemiology of preeclampsia and eclampsia in the United States, 1979–1986. Am J Obstet Gynecol 1990; 163: 460–5PubMedGoogle Scholar
  3. 3.
    Rosenfield A, Maine D. Maternal mortality — a neglected tragedy. Where is the M in MCH? Lancet 1985; II (8446): 83–5Google Scholar
  4. 4.
    Duley L. Maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, Latin America and Caribbean. Br J Obstet Gynaecol 1992; 99: 547–53PubMedCrossRefGoogle Scholar
  5. 5.
    Redman CWG, Jefferies M. Revised definition of pre-eclampsia. Lancet; 1988: 1: 809–12PubMedCrossRefGoogle Scholar
  6. 6.
    Australasian Society for the Study of Hypertension in Pregnancy. Consensus statement: management of hypertension in pregnancy: executive summary. Med J Aust 1993; 158: 700–2Google Scholar
  7. 7.
    Brown MA, Buddie ML. What’s in a name? Problems with the classification of hypertension in pregnancy. J Hypertens 1997; 15: 1049–54PubMedCrossRefGoogle Scholar
  8. 8.
    Lazard EM. Apreliminary report on the intravenous use of magnesium sulphate in puerperal eclampsia. Am J Obstet Gynecol 1925; 9: 178–88Google Scholar
  9. 9.
    The Eclampsia Trial Collaborative Group. Which anticonvulsant for women with eclampsia? Evidence from the collaborative eclampsia trial. Lancet 1995; 345: 1455–63Google Scholar
  10. 10.
    Lucas MJ, Leveno KJ, Cunningham FG. A comparison of magnesium sulfate with phenytoin for the prevention of eclampsia. N Engl J Med 1995; 333: 201–5PubMedCrossRefGoogle Scholar
  11. 11.
    Coetzee EJ, Dommisse J, Anthony J. A randomised controlled trial of intravenous magnesium sulphate versus placebo in the management of women with pre-eclampsia. Br J Obstet Gynaecol 1998; 105: 300–3PubMedCrossRefGoogle Scholar
  12. 12.
    Sibai BM. Management of preeclampsia. Clin Perinatol 1991; 18: 793–808PubMedGoogle Scholar
  13. 13.
    Duley L, Neilson JP. Magnesium sulphate and pre-eclampsia. Trial needed to see whether it’s as valuable in pre-eclampsia as in eclampsia. BMJ 1999; 319: 3–4PubMedCrossRefGoogle Scholar
  14. 14.
    Sibai BM, Spinnato JA, Watson DL, et al. Effect of magnesium sulfate on electroencephalographic findings in pre-eclampsia-eclampsia. Obstet Gynecol 1984; 64: 261–6PubMedGoogle Scholar
  15. 15.
    Del Castillo J, Engbaek L. The nature of neuromuscular block produced by magnesium. J Physiol 1954; 124: 370–3Google Scholar
  16. 16.
    Idama TO, Lindow SW Magnesium sulphate: areview of clinical pharmacology applied to obstetrics. Br J Obstet Gynecol 1998; 105: 260–8CrossRefGoogle Scholar
  17. 17.
    Villar MA, Sibai BM. Eclampsia. Obstet Gynecol Clin North Am 1988; 15: 355–77PubMedGoogle Scholar
  18. 18.
    Friedman SA. Pre-eclampsia: areview oftheroleofprostaglandins. Obstet Gynecol 1988; 71: 122–37PubMedGoogle Scholar
  19. 19.
    Watson KV, Moldow CF, Ogburn PL, et al. Magnesium sulfate: rationale for its use in pre-eclampsia. Proc Natl Acad Sci USA 1986; 83: 1075–8PubMedCrossRefGoogle Scholar
  20. 20.
    Sipes LS, Weiner CP, Gellhaus TM, et al. Effect of magnesium sulphate infusion upon plasma prostaglandins in pre eclamptic and pre term labour. Hypertens Preg 1994; 13: 293–302CrossRefGoogle Scholar
  21. 21.
    Belfort MA, Moise Jr KJ. Effect of magnesium sulfate on maternal brain blood flow in pre-eclampsia: a randomized, placebo-controlled study. Am J Obstet Gynecol 1992; 167: 661–6PubMedGoogle Scholar
  22. 22.
    Naidu S, Payne AJ, Moodley J, et al. Randomized study assessing the effect of phenytoin and magnesium sulphate on maternal cerebral circulation in eclampsia using transcranial Doppler ultrasound. Br J Obstet Gynaecol 1996; 103: 111–6PubMedCrossRefGoogle Scholar
  23. 23.
    Watkins JC, Evans RH. Excitatory amino acids transmitters. Annu Rev Pharmacol Toxicol 1981; 21: 165–204PubMedCrossRefGoogle Scholar
  24. 24.
    Watkins JC. Excitatory amino acids and central synaptic transmission. Trends Pharmacol 1984; 5: 373–76CrossRefGoogle Scholar
  25. 25.
    Cotton DB, Hallak M, Janusz C, et al. Central anticonvulsant effects of magnesium sulphate on N-methyl-D-aspartate-induced seizures. Am J Obstet Gynecol 1993; 168: 974–8PubMedGoogle Scholar
  26. 26.
    Cotton DB, Janusz CA, Berman R. Anticonvulsant effects of magnesium sulphate on hippocampal seizures. Therapeutic implications in pre eclampsia-eclampsia. Am J Obstet Gynecol 1992; 166: 1127–36PubMedGoogle Scholar
  27. 27.
    Sibai BM, Lipshitz J, Anderson GD, et al. Reassessment of intravenous MgSO4 therapy in pre-eclampsia-eclampsia. Obstet Gynecol 1981; 57: 199–201PubMedGoogle Scholar
  28. 28.
    Pritchard JA. The use of magnesium ion in the management of eclamptogenic toxemias. Surg Gynecol Obstet 1955; 100: 131–40PubMedGoogle Scholar
  29. 29.
    Flowers CE, Eastetrics WE, White FD, et al. Magnesium sulfate in toxemia of pregnancy. Obstet Gynecol 1962; 19: 315–27PubMedGoogle Scholar
  30. 30.
    Chesley LC, Tepper I. Plasma levels of magnesium attained in magnesium sulfate therapy for pre-eclampsia and eclampsia. Surg Clin North Am 1957; 37: 353–67PubMedGoogle Scholar
  31. 31.
    Chesley LC, Tepper I. Some effects of magnesium loading upon renal excretion of magnesium and certain other electrolytes. J Clin Invest 1958; 37: 1362–72PubMedCrossRefGoogle Scholar
  32. 32.
    Handwerker SM, Altura BT, Chi DS, et al. Serum ionized magnesium levels during intravenous MgSO4 therapy of preeclamptic women. Acta Obstet Gynecol Scand 1995; 74: 517–9PubMedCrossRefGoogle Scholar
  33. 33.
    Chesley LC. Parenteral magnesium sulfate and the distribution, plasma levels, and excretion of magnesium. Am J Obstet Gynecol 1979; 133: 1–7PubMedGoogle Scholar
  34. 34.
    Peiker G, Muller B, Erdmanm M, et al. The pharmacokinetics of magnesium sulfate in pregnant women with threatened abortion and fetal retardation. Pharmazie 1987; 42: 531–2PubMedGoogle Scholar
  35. 35.
    Wang YL, Chen G. Pharmacodynamic modeling of cardiovascular effects of magnesium in pregnancy induced hypertensive gravidas. Chin J Clin Pharmacol 1994; 10 (2): 87–92.Google Scholar
  36. 36.
    Flowers CE. Magnesium sulfate in obstetrics. A study of magnesium in plasma, urine, and muscle. Am J Obstet Gynecol 1965; 91: 763–5PubMedGoogle Scholar
  37. 37.
    Hall DG. Serum magnesium in pregnancy. Obstet Gynecol 1957; 9 (2): 158–66.PubMedGoogle Scholar
  38. 38.
    Brandt LJ, Glaser W, Jones A. Soft tissue distribution and plasma disappearance of intravenously administered isotopic magnesium with observations on uptake in bone. Metabolism 1958; 7: 355–61PubMedGoogle Scholar
  39. 39.
    Fong J, Gurewitsch ED, Volpe L, et al. Baseline serum and cerebrospinal fluid magnesium levels in normal pregnancy and pre-eclampsia. Obstet Gynecol 1995; 85 (3): 444–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Thurnau GR, Kemp DB, Jarvis A. Cerebrospinal fluid levels of magnesium in patients with pre-eclampsia after treatment with intravenous magnesium sulfate: a preliminary report. Am J Obstet Gynecol 1987; 157: 1435–8PubMedGoogle Scholar
  41. 41.
    Oppelt WW, Macintyre I, Rail DP. Magnesium exchange between blood and cerebrospinal fluid. Am JPhysiol 1963; 205: 959–62Google Scholar
  42. 42.
    Aikawa J, Bruns PD. Placental transfer and fetal tissue uptake of Mg2+in the rabbit. Proc Soc Exp Biol Med 1960; 105: 957–9Google Scholar
  43. 43.
    Mcguinness GA, Weinstein MM, Cruikshank DP, et al. Effect of magnesium sulfate treatment on perinatal calcium metabolism. II: neonatal responses. Obstet Gynecol 1980; 56: 595–600PubMedGoogle Scholar
  44. 44.
    Cruikshank DP, Varner MW, Pitkin RM. Breast milk magnesium and calcium concentrations following magnesium sulfate treatment. Am J Obstet Gynecol 1982; 143: 685–8PubMedGoogle Scholar
  45. 45.
    Cruikshank DP, Pitkin RM, Donnelly E, et al. Urinary magnesium, calcium, and phosphate excretion during magnesium sulfate infusion. Obstet Gynecol 1981; 58: 430–4PubMedGoogle Scholar
  46. 46.
    Chen G, Li QN, Guo N. Studies on the pharmacokinetics and pharmacodynamics of MgSO4 in the treatment of pregnancyinduced hypertension. Chin J Clin Pharmacol 1991; 7 (2): 108–11.Google Scholar
  47. 47.
    Carney SL. Effect of magnesium deficiency on renal magnesium. J Clin Invest 1980; 65: 180–8PubMedCrossRefGoogle Scholar
  48. 48.
    Cruikshank DP, Pitkin RM, Reynolds WA, et al. Effects of magnesium sulfate treatment on perinatal calcium metabolism. I: maternal and fetal responses. Am J Obstet Gynecol 1979; 134: 243–9PubMedGoogle Scholar
  49. 49.
    Petrie RH. Tocolysis using magnesium sulfate. Semin Perinatal 1981; 5: 266–73Google Scholar
  50. 50.
    Perticone F, Adinolfi L, Bonaduce D. Efficacy of magnesium sulfate in the treatment of torsade de pointes. Am Heart J 1986; 112: 847–9PubMedCrossRefGoogle Scholar
  51. 51.
    Morris ME, LeRoy S, Sutton SC. Absorption of magnesium from orally administered magnesium sulfate in man. Clin Toxicol 1987; 25: 371–82CrossRefGoogle Scholar
  52. 52.
    Zuspan FP Treatment of severe pre-eclampsia and eclampsia. Clin Obstet Gynecol 1966; 9: 945–72Google Scholar
  53. 53.
    Pritchard JA. The use of magnesium sulfate in pre-eclampsiaeclampsia. J Reproduct Med 1979; 23: 107–14Google Scholar
  54. 54.
    Sibai BM, Graham JM, McCubbin JH. A comparison of intravenous and intramuscular magnesium sulfate regimens in preeclampsia. Am J Obstet Gynecol 1984; 150: 728–33PubMedGoogle Scholar
  55. 55.
    Sibai BM. Magnesium sulphate is the ideal anticonvulsant in pre-eclampsia-eclampsia. Am J Obstet Gynecol 1990; 162: 1141–5PubMedGoogle Scholar
  56. 56.
    Winkler AW, Smith PK, Hoff HE. Intravenous magnesium sulphate in the treatment of nephritic convulsions in adults. J Clin Invest 1942; 21: 207–16PubMedCrossRefGoogle Scholar
  57. 57.
    McCubbin JH, Sibai BM, Abdella TN, et al. Cardiorespiratory arrest due to acute maternal hypermagnesaemia. Lancet 1981; I (8228): 1058.CrossRefGoogle Scholar
  58. 58.
    Monif GRG, Savory J. Iatrogenic maternal hypocalcaemia following magnesium sulphate therapy. JAMA 1972; 219: 1469–70PubMedCrossRefGoogle Scholar
  59. 59.
    Eisenbud E, Lobue CC. Hypocalcaemia after therapeutic use of magnesium sulphate. Arch Intern Med 1976; 136: 688–91PubMedCrossRefGoogle Scholar
  60. 60.
    Lipsitz PJ, English IC. Hypermagnesemia in the newborn infant. Pediatrics 1967; 40: 856–62PubMedGoogle Scholar
  61. 61.
    Stone SR, Pritchard JA. Effect of maternally administered magnesium sulfate in the neonate. Obstet Gynecol 1970; 35: 574–7PubMedGoogle Scholar
  62. 62.
    Nelson KB, Grether JK. Can magnesium sulfate reduce the risk of cerebral palsy in very low birthweight infants? Pediatrics 1995; 95: 263–9PubMedGoogle Scholar
  63. 63.
    Schendel DE, Berg CJ, Yeargin-Allsopp M, et al. Prenatal magnesium sulfate exposure and the risk for cerebral palsy or mental retardation among very low-birth-weight children aged 3 to 5 years. JAMA 1996; 276: 1805–11PubMedCrossRefGoogle Scholar
  64. 64.
    Paneth N, Jetton J, Pintomartin J, et al. Magnesium sulfate in labor and risk of neonatal brain lesions and cerebral palsy in low birthweight infants. Pediatrics 1997; 99: Ell–6CrossRefGoogle Scholar
  65. 65.
    Mittendorf R, Covert R, Boman J, et al. Is tocolytic magnesium sulphate associated with increased total paediatric mortality? Lancet 1997; 350: 1517–8PubMedCrossRefGoogle Scholar
  66. 66.
    Ghoneim MM, Long JP The interaction between magnesium and other neuromuscular blocking agents. Anesthesiology 1970; 32: 23–7PubMedCrossRefGoogle Scholar
  67. 67.
    Baraka A, Yazigi A. Neuromuscular interaction of magnesium with succinylcholine-vecuronium sequence in the eclamptic parturient. Anesthesiology 1987; 67: 806–8PubMedCrossRefGoogle Scholar
  68. 68.
    Vincent RD, Chestnut DH, Sipes SL, etal. Magnesium sulphate decreases maternal blood pressure but not uterine blood flow during epidural anaesthesia in gravid ewes. Anesthesiology 1991; 74: 77–82PubMedCrossRefGoogle Scholar
  69. 69.
    Lin CC, Pielet BW, Poon E, et al. Effect of magnesium sulphate on fetal heart rate variability in pre eclamptic patients during labour. Am J Perinatal 1988; 5: 208–13CrossRefGoogle Scholar
  70. 70.
    Fenakel K, Fenakel G, Appleman Z, et al. Nifedipine in the treatment of severe pre-eclampsia. Obstet Gynecol 1991; 77: 331–7PubMedGoogle Scholar

Copyright information

© Adis International Limited 2000

Authors and Affiliations

  1. 1.Department of Clinical PharmacologyJingling HospitalNanjing P.R.China
  2. 2.Pharmacy ResearchHartford HospitalHartfordUSA

Personalised recommendations