Population Pharmacokinetics of Magnesium Sulfate in Preeclampsia and Associated Factors

• Published in: Drugs in R&D 2020-09, Vol.20 (3), p.257-266
• Main Authors: da Costa, Tatiana Xavier, Azeredo, Francine Johansson, Ururahy, Marcela Abbott Galvão, da Silva Filho, Miguel Adelino, Martins, Rand Randall, Oliveira, Antonio Gouveia
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anticonvulsants - administration & dosage; Anticonvulsants - blood; Anticonvulsants - pharmacokinetics; Clinical Protocols; Cohort Studies; Female; Humans; Infusions, Intravenous; Internal Medicine; Magnesium Sulfate - administration & dosage; Magnesium Sulfate - blood; Magnesium Sulfate - pharmacokinetics; Medicine; Medicine & Public Health; Original; Original Research Article; Pharmacology/Toxicology; Pharmacotherapy; Pre-Eclampsia - blood; Pre-Eclampsia - drug therapy; Pre-Eclampsia - prevention & control; Pregnancy; Prospective Studies; Young Adult
• ISSN: 1174-5886; 1179-6901
• DOI: 10.1007/s40268-020-00315-2

Background and Objective The pharmacokinetic basis of magnesium sulphate (MgSO 4 ) 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 MgSO 4 in PE, and to determine key covariates having an effect in MgSO 4 pharmacokinetics in preeclampsia (PE) and to determine key covariates having an effect in MgSO 4 PK. Methods A prospective cohort study was conducted from June 2016 to February 2018 in patients with PE administered MgSO 4 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 MgSO 4 [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 MgSO 4 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 MgSO 4 CL and V , respectively. The model was parameterized as CL and V . Conclusion The PK of MgSO 4 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 MgSO 4 . Pregnant women with PE and a higher serum creatinine value show lower CL and, therefore, lower MgSO 4 elimination rate.