Pharmacokinetics and placental transfer of magnesium sulfate in pregnant women

详细信息    查看全文

• 作者：Kathleen F. Brookfield ; MD ; PhD ; MPH^a ; ^{brookfie@ohsu.edu" class="auth_mail" title="E-mail the corresponding author} ; Felice Su ; MD^b ; Mohammed H. Elkomy ; PhD^d ; David R. Drover ; MD^c ; Deirdre J. Lyell ; MD^a ; Brendan Carvalho ; MBBCh ; FRCA^c
• 关键词：magnesium sulfate ; neuroprotection ; NONMEM ; pharmacokinetics ; pregnancy
• 刊名：American Journal of Obstetrics and Gynecology
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：214
• 期：6
• 页码：737.e1-737.e9
• 全文大小：752 K

文摘

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.

Objective

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.

Study Design

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.

Results

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.

Conclusions

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.