Abstract:Objective To establish a population pharmacokinetic model of magnesium sulfate for the prevention and treatment of pre-eclampsia and apply it in clinical practice. Methods The medical records of patients who receiving magnesium sulfate treatment for pre-eclampsia in the ICU ward of Obstetrics and Gynecology Hospital of Tongji University from July 2018 to October 2023 were retrospectively reviewed. The data of the patients were collected, such as age, height, weight, serum creatinine, creatinine clearance, body mass index(BMI), body surface area, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, albumin levels, and concurrent use of medicine, including furosemide, insulin, beta-blockers, calcium channel blockers, human albumin, and fibrinogen. The nonlinear mixed effects model(NONMEM) software was used to estimate the pharmacokinetic model parameters and covariates for magnesium sulfate. Goodness-of-fit plots and Bootstrap were used for model evaluation. The final model was used to simulate and estimate magnesium sulfate dosage for different covariate populations. Results A total of 101 patients and 429 magnesium ion concentrations were included in the analysis. A first-order elimination two-compartment model was fitted, with a baseline magnesium concentration of 0.772 mmol/L. The typical values for CL, V1, Q, and V2 was 3.29 L/h, 21.5 L, 4.17 L/h, and 23.3 L, respectively. Serum creatinine was found to be a significant covariate that affected the clearance of magnesium sulfate in patients. Maintenance doses of magnesium sulfate to achieve a target concentration of 2 mmol/L was 2, 1.5, and 1 g/h for serum creatinine values <50, 50-90, and >90 μmol/L, respectively. Conclusion This population pharmacokinetic model can facilitate the precise use of magnesium sulfate for the prevention and treatment of pre-eclampsia in clinical practice.
