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175: Pharmacokinetics of magnesium sulfate in pregnant women
Poster Session I
175 Pharmacokinetics of magnesium sulfate in pregnant women
Kathleen Brookfield1, Felice Su2, David Drover3, Maria Adelus3, Deirdre Lyell1, Brendan Carvalho3
ajog.org
Figure A: Observed versus individual predicted magnesium concentrations in pregnant women receiving intravenous MgSO4
1 Stanford University School of Medicine, Department of Obstetrics & Gynecology, Stanford, CA, 2Stanford University, Pediatrics, Stanford, CA, 3 Stanford University, Anesthesiology, Stanford, CA
OBJECTIVE: Under or over-dosing of magnesium sulfate (MgSO4) may result in fetal/maternal harm. Data are limited on MgSO4 pharmacokinetics (PK) and related pharmacodynamics (PD), which are key to establishing optimized treatment regimens. We sought to characterize the PK of MgSO4 in pregnant women so that optimal, PK/PD-derived dosing schedules can be determined for women receiving MgSO4 for obstetric indications. STUDY DESIGN: From 10/2012 - 5/2014, pregnant women with preeclampsia, preterm labor, or prematurity (< 32 wks) and prescribed MgSO4 were consented to participate in this prospective, IRBapproved study. Women received a 4g loading dose, and a 2g/h maintenance dose. Maternal blood samples were obtained at baseline, 30 min, 1 h, 2 h, 4 h, and q6 h during MgSO4 infusion; and at 1 h, 3 h, 6 h, 9 h, and 12 h after MgSO4 was discontinued. Neonatal and cord blood were also sampled. A two-compartment linear disposition model was used to describe PK data with nonlinear mixed-effects modeling and visual predictive check for estimated modeling of observed and predicted serum MgSO4 concentrations. RESULTS: 1,156 serum magnesium samples were collected from 151 pregnant women, neonates, and cord blood. The base model adequately predicted the maternal serum magnesium concentrations after MgSO4 administration.(Figure A) The mean population parameter estimates were: clearance 2.8 L/h; intercompartmental clearance 244 L/h central volume of distribution 14.1 L; and peripheral volume of distribution 96.4 L. The model predictions changed significantly with additional covariates (age, BMI, creatinine). Maternal and umbilical cord Mg levels were highly correlated (p<0.001).(Figure B) CONCLUSION: The study accurately characterizes the PK of MgSO4 administered to pregnant women. Further PK exploration will include evaluation of how predicted serum Mg concentrations change with alterations in covariates. These PK findings are a crucial step in creating PK/PD optimized treatment protocols to facilitate MgSO4 dosing to optimize therapeutic efficacy while minimizing harm.
Figure B: Correlation of maternal serum and umbilical cord magnesium levels. Pearson correlation coefficient ¼ 0.888 (p<0.001)
176 Recent center level data may be more appropriate for periviable counseling versus the historic NICHD cohort
Kathryn Davidson1, David Burchfield2, Oluseyi Ogunleye1, Anushka Chelliah1, Monique Ho1, Robert Egerman1, Anthony Gregg1
1 University of Florida, Maternal Fetal Medicine, Gainesville, FL, 2University of Florida, Neonatology, Gainesville, FL
OBJECTIVE: Recent periviable survival rates at our institution seemed higher than rates calculated from the multi-center data utilized in the NICHD calculator. Therefore, we sought to analyze our own recent outcomes to determine if our mortality rates differed significantly from this historic cohort. STUDY DESIGN: We performed a retrospective analysis of recent (2011-2013) periviable births (22+0 to 25+6) at our tertiary academic institution reported to the Vermont Oxford Network versus
S102 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2015
175 Pharmacokinetics of magnesium sulfate in pregnant women
Kathleen Brookfield1, Felice Su2, David Drover3, Maria Adelus3, Deirdre Lyell1, Brendan Carvalho3
ajog.org
Figure A: Observed versus individual predicted magnesium concentrations in pregnant women receiving intravenous MgSO4
1 Stanford University School of Medicine, Department of Obstetrics & Gynecology, Stanford, CA, 2Stanford University, Pediatrics, Stanford, CA, 3 Stanford University, Anesthesiology, Stanford, CA
OBJECTIVE: Under or over-dosing of magnesium sulfate (MgSO4) may result in fetal/maternal harm. Data are limited on MgSO4 pharmacokinetics (PK) and related pharmacodynamics (PD), which are key to establishing optimized treatment regimens. We sought to characterize the PK of MgSO4 in pregnant women so that optimal, PK/PD-derived dosing schedules can be determined for women receiving MgSO4 for obstetric indications. STUDY DESIGN: From 10/2012 - 5/2014, pregnant women with preeclampsia, preterm labor, or prematurity (< 32 wks) and prescribed MgSO4 were consented to participate in this prospective, IRBapproved study. Women received a 4g loading dose, and a 2g/h maintenance dose. Maternal blood samples were obtained at baseline, 30 min, 1 h, 2 h, 4 h, and q6 h during MgSO4 infusion; and at 1 h, 3 h, 6 h, 9 h, and 12 h after MgSO4 was discontinued. Neonatal and cord blood were also sampled. A two-compartment linear disposition model was used to describe PK data with nonlinear mixed-effects modeling and visual predictive check for estimated modeling of observed and predicted serum MgSO4 concentrations. RESULTS: 1,156 serum magnesium samples were collected from 151 pregnant women, neonates, and cord blood. The base model adequately predicted the maternal serum magnesium concentrations after MgSO4 administration.(Figure A) The mean population parameter estimates were: clearance 2.8 L/h; intercompartmental clearance 244 L/h central volume of distribution 14.1 L; and peripheral volume of distribution 96.4 L. The model predictions changed significantly with additional covariates (age, BMI, creatinine). Maternal and umbilical cord Mg levels were highly correlated (p<0.001).(Figure B) CONCLUSION: The study accurately characterizes the PK of MgSO4 administered to pregnant women. Further PK exploration will include evaluation of how predicted serum Mg concentrations change with alterations in covariates. These PK findings are a crucial step in creating PK/PD optimized treatment protocols to facilitate MgSO4 dosing to optimize therapeutic efficacy while minimizing harm.
Figure B: Correlation of maternal serum and umbilical cord magnesium levels. Pearson correlation coefficient ¼ 0.888 (p<0.001)
176 Recent center level data may be more appropriate for periviable counseling versus the historic NICHD cohort
Kathryn Davidson1, David Burchfield2, Oluseyi Ogunleye1, Anushka Chelliah1, Monique Ho1, Robert Egerman1, Anthony Gregg1
1 University of Florida, Maternal Fetal Medicine, Gainesville, FL, 2University of Florida, Neonatology, Gainesville, FL
OBJECTIVE: Recent periviable survival rates at our institution seemed higher than rates calculated from the multi-center data utilized in the NICHD calculator. Therefore, we sought to analyze our own recent outcomes to determine if our mortality rates differed significantly from this historic cohort. STUDY DESIGN: We performed a retrospective analysis of recent (2011-2013) periviable births (22+0 to 25+6) at our tertiary academic institution reported to the Vermont Oxford Network versus
S102 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2015