Magnesium sulfate in eclampsia and pre-eclampsia pharmacokinetic principles

Magnesium sulfate (MgSO4) is the agent most commonly used for treatment of eclampsia and prophylaxis of eclampsia in patients with severe pre-eclampsi a. It is usually given by either the intramuscular or intravenous routes. T he intramuscular regimen is most commonly a 4g intravenous loading dose, im mediately followed by 10g intramuscularly and then by 5g intramuscularly ev ery 4 hours in alternating buttocks. The intravenous regimen is given as a 4g dose, followed by a maintenance infusion of 1 to 2 gk by controlled infu sion pump. After administration, about 40% of plasma magnesium is protein bound. The u nbound magnesium ion diffuses into the extravascular-extracellular space, i nto bone, and across the placenta and fetal membranes and into the fetus an d amniotic fluid. In pregnant women, apparent volumes of distribution usual ly reach constant values between the third and fourth hours after administr ation, 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 ho urs after an intravenous infusion of MgSO4 The pharmacokinetic profile of M gSO4 after intravenous administration can be described by a 2-compartment m odel with a rapid distribution (a) phase, followed by a relative slow beta phase of elimination. The clinical effect and toxicity of MgSO4 can be linked to its concentratio n in plasma. A concentration of 1.8 to 3.0 mmol/L has been suggested for tr eatment of eclamptic convulsions. The actual magnesium dose and concentrati on needed for prophylaxis has never been estimated. Maternal toxicity is ra re when MgSO4 is 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, an d cardiac arrest can be expected when concentrations of magnesium exceed 12 .5 mmol/L. Careful attention to the monitoring guidelines can prevent toxic ity. Deep tendon reflexes, respiratory rate, urine output and serum concent rations are the most commonly followed variables. In this review, we will outline the currently available knowledge of the ph armacokinetics of MgSO4 and its clinical usage for women with pre-eclampsia and eclampsia.