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.

中文翻译：

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先兆子痫中硫酸镁的种群药代动力学及相关因素。

背景与目的

尚未明确建立先兆子痫（PE）预防和治疗的硫酸镁（MgSO ₄）给药方案的药代动力学基础。研究的目的是建立PE中MgSO ₄的群体药代动力学（PK）模型，确定先兆子痫（PE）中对MgSO ₄药代动力学有影响的关键协变量，并确定对MgSO ₄ PK有影响的关键协变量。

方法

从2016年6月至2018年2月对前瞻性队列研究进行了研究，对以4克大剂量推注MgSO _4的PE患者以1 g / h的速率连续输注。在治疗给药之前和初始剂量后2、6、12和18小时获得血清镁浓度。Monolix软件用于估计MgSO _4的群体PK参数[清除率（CL），分布量（V），半衰期]，并开发具有基线患者人口统计学，临床和实验室协变量的PK模型。

结果

研究人群包括109名患者。一室PK模型充分描述了MgSO ₄的PK曲线。人口CL的模型估计为1.38 L / h；对于V来说是13.3 L; 基线镁浓度为0.77 mmol / L（1.87 mg / dL）。基线体重和血清肌酐的影响统计学硫酸镁₄ CL和V分别。该模型参数化为CL和V。

结论

肌酐和体重显着影响PE孕妇中MgSO ₄的PK 。PE和体重较高的孕妇的V较高，因此MgSO _4的消除率较低。PE和血清肌酐值较高的孕妇显示出较低的CL，因此，较低的MgSO ₄消除率。