Population Pharmacokinetics of Magnesium Sulfate in Preeclampsia and Associated Factors

The pharmacokinetic basis of magnesium sulphate (MgSO₄) dosing regimens for preeclampsia (PE) prophylaxis and treatment is not clearly established. The aim of study is to develop a population pharmacokinetic (PK) model of MgSO₄ in PE, and to determine key covariates having an effect in MgSO₄ pharmacokinetics in preeclampsia (PE) and to determine key covariates having an effect in MgSO₄ PK.

A prospective cohort study was conducted from June 2016 to February 2018 in patients with PE administered MgSO₄ as a 4-g bolus followed by continuous infusion at a rate of 1 g/h. Serum magnesium concentrations were obtained before treatment administration and 2, 6, 12, and 18 h after the initial dose. The software Monolix was used to estimate population PK parameters of MgSO₄ [clearance (CL), volume of distribution (V), half-life] and to develop a PK model with baseline patient demographic, clinical, and laboratory covariates.

The study population consisted of 109 patients. The PK profile of MgSO₄ was adequately described by a one-compartment PK model. The model estimate of the population CL was 1.38 L/h; for V, it was 13.3 L; and the baseline magnesium concentration was 0.77 mmol/L (1.87 mg/dL). The baseline body weight and serum creatinine statistically influenced MgSO₄ CL and V, respectively. The model was parameterized as CL and V.

The PK of MgSO₄ in pregnant women with PE is significantly affected by creatinine and body weight. Pregnant women with PE and higher body weight have a higher V and, consequently, a lower elimination rate of MgSO₄. Pregnant women with PE and a higher serum creatinine value show lower CL and, therefore, lower MgSO₄ elimination rate.