Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA.
Department of Pediatric Critical Care, Stanford University School of Medicine, Stanford, CA.
Am J Obstet Gynecol. 2016 Jun;214(6):737.e1-9. doi: 10.1016/j.ajog.2015.12.060. Epub 2016 Jan 6.
Magnesium sulfate is one of the most commonly prescribed intravenous medications in obstetrics. Despite its widespread use, there are limited data about magnesium pharmacokinetics, and magnesium is prescribed empirically without dose adjustment for different indications.
The aim of this study was to characterize the pharmacokinetics and placental transfer of magnesium sulfate in pregnant women and to determine key covariates that impact the pharmacokinetics.
This is a prospective pharmacokinetic cohort study of pregnant women who were prescribed magnesium sulfate for preeclampsia, preterm labor, or extreme prematurity. Women received a 4-g loading dose and 2 g/h maintenance dose as clinically indicated. Maternal blood samples were obtained before and at multiple time points during and after magnesium administration. Cord blood also was sampled at delivery. A population pharmacokinetic approach that used a nonlinear mixed-effects modeling was used to characterize magnesium disposition.
Pharmacokinetic profiles of 111 pregnant women were analyzed. Magnesium clearance was 3.98 L/h in preeclamptic women and 5.88 L/h non-preeclamptic women. Steady-state concentration of magnesium was 7.2 mg/dL in preeclamptic women compared with 5.1 mg/dL in non-preeclamptic women. Maternal weight significantly impacted time to steady state. The ratio of the mean umbilical vein magnesium level to the mean maternal serum magnesium level at the time of delivery was 0.94 ± 0.15.
The study accurately characterizes the pharmacokinetics of magnesium administered to pregnant women. Preeclamptic status and maternal weight significantly impact serum magnesium levels. This pharmacokinetic model could be applied to larger cohorts to help tailor magnesium treatment and account for these covariates.
硫酸镁是产科最常用的静脉内给药药物之一。尽管它的应用广泛，但关于镁的药代动力学数据有限，并且镁是根据不同的适应证经验性给药而不进行剂量调整。
本研究旨在描述硫酸镁在孕妇中的药代动力学和胎盘转运，并确定影响药代动力学的关键协变量。
这是一项针对因子痫前期、早产或极早产而接受硫酸镁治疗的孕妇的前瞻性药代动力学队列研究。根据临床指征，孕妇接受 4g 负荷剂量和 2g/h 维持剂量。在硫酸镁给药前、给药期间和给药后多个时间点采集母体血样，并在分娩时采集脐血样。采用非线性混合效应模型进行群体药代动力学分析，以描述镁的处置。
分析了 111 名孕妇的药代动力学特征。子痫前期孕妇的镁清除率为 3.98 L/h，非子痫前期孕妇为 5.88 L/h。子痫前期孕妇的镁稳态浓度为 7.2mg/dL，而非子痫前期孕妇为 5.1mg/dL。母体体重显著影响达到稳态的时间。分娩时脐带静脉镁水平与母体血清镁水平的平均值比值为 0.94±0.15。
本研究准确描述了硫酸镁在孕妇中的药代动力学。子痫前期状态和母体体重显著影响血清镁水平。该药代动力学模型可应用于更大的队列，以帮助调整镁的治疗并考虑这些协变量。
