///2014 Abstract Details
2014 Abstract Details2019-07-18T14:34:47+00:00

Pharmacokinetics and Placental Transfer of Magnesium Sulfate in Pregnant Women

Abstract Number: GM-05
Abstract Type: Original Research

Kathleen F Brookfield MD, PhD, MPH1 ; Felice Su MD2; David R. Drover MD3; Maria L. Adelus BA4; Deirdre J. Lyell MD5; Brendan Carvalho MD6

Introduction: Magnesium sulfate (MS) is one of the most commonly prescribed intravenous medications in obstetrics, and is used for seizure prophylaxis in preeclampsia, tocolysis in threatened preterm labor, and neuroprotection of extreme preterm (< 32 wks gestation) fetuses (1). Maternal and fetal harm may result from under- or over-dosing of MS (2). Despite wide-spread use, there is limited data about MS pharmacokinetics (PK). The aim of this study was to characterize the PK and placental transfer of MS in pregnant women.

Methods: Pregnant women admitted to the hospital with preeclampsia, preterm labor or extreme prematurity, and prescribed MS were consented to participate in this prospective, IRB-approved study. Women received a 4g loading dose (over 20 min) and a 2g/hr maintenance dose of MS as clinically indicated. Maternal blood samples were obtained prior to MS administration; 30 min, 1 hr, 2 hr, 4 hr, and every 6 hr during MS administration; and 1 hr, 3 hr, 6 hr, 9 hr, and 12 hr after MS was discontinued. Cord blood was also sampled for MS at delivery. A population PK approach was used to analyze MS levels. A two-compartment linear disposition model with nonlinear mixed-effects modeling and visual predictive check was used for PK modeling of observed and predicted serum MS concentrations.

Results: PK profiles of 56 pregnant women in this ongoing study were analyzed. Maternal data was best described using a two-compartment model. The model adequately predicted the individual serum MS concentrations after MS administration (Figure A). The mean population parameter estimates were: clearance 2.92 mL/min; inter-compartmental clearance 5.05 mL/min central volume of distribution 0.93 L; and peripheral volume of distribution 7.04 L. MS readily crossed the placenta; maternal serum and umbilical cord MS levels were highly correlated (Figure B).

Conclusions:

The study accurately characterizes the PK of MS administered to pregnant women. Covariate PK analysis and maternal/neonatal pharmacodynamics (PD) determinations are currently ongoing. These reported PK findings are a key first step to creating PK-PD optimized treatment protocols. Tailoring MS treatment protocols will advance the management of preeclampsia seizure prophylaxis, preterm tocolysis, and fetal neuroprotection by maximizing the benefits of MS exposure while minimizing unwanted maternal and neonatal side effects.

References:

1. Obstet Gynecol 2009;114: 669-73

2. Obstet Gynecol 2007;110: 61-7



SOAP 2014