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Observational Study
. 2020 Sep;20(3):257-266.
doi: 10.1007/s40268-020-00315-2.

Population Pharmacokinetics of Magnesium Sulfate in Preeclampsia and Associated Factors

Tatiana Xavier da Costa  1   2   3 , Francine Johansson Azeredo  4 , Marcela Abbott Galvão Ururahy  5 , Miguel Adelino da Silva Filho  6 , Rand Randall Martins  7 , Antonio Gouveia Oliveira  7
Affiliations
Observational Study

Population Pharmacokinetics of Magnesium Sulfate in Preeclampsia and Associated Factors

Tatiana Xavier da Costa et al. Drugs R D. 2020 Sep.

Abstract

Background and objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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Conflict of interest statement

The authors, Tatiana Xavier da Costa, Francine Johansson Azeredo, Marcela Abbott Galvão Ururahy, Miguel Adelino da Silva Filho, Rand Randall Martins, and Antonio Gouveia Oliveira, declare that there is no conflict of interest.

Figures

Fig. 1
Fig. 1
Correlation between observed plasma concentration and population plasma concentration (left) and with individual predicted values (right)
Fig. 2
Fig. 2
Distribution of residuals. a Representation of the normal distribution of residuals. The dashed line represents the theoretical distribution defined in the developed model and the bars the distribution of the observed data. b Homogeneous distribution of weighted residuals in relation to time. c Homogeneous distribution of weighted residuals in relation to predicted plasma concentration. IWRES weighted individual residual, NPDE normalized predicted errors, PWRES weighted population residual
Fig. 3
Fig. 3
Predicted versus observed concentrations of MgSO4 over infusion time (VPC). The dotted lines represent the 5th, 50th, and 95th percentiles of the simulated data. The areas indicate the range of 90% predicted associated with the 5th, 50th, and 95th percentiles of the simulated data. The blue circles correspond to the observed values and the black circles to the predicted values. VPC visual predictive check
See this image and copyright information in PMC

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