Donald B Wiest1, Eugene Chang2, Deanna Fanning3, Sandra Garner4, Toby Cox4, Dorothea D Jenkins3. 1. Department of Clinical Pharmacy & Outcome Sciences, Medical University of South Carolina, Charleston, SC. Electronic address: wiestdb@musc.edu. 2. Department of Obstetrics & Gynecology, Medical University of South Carolina, Charleston, SC. 3. Department of Pediatrics, Medical University of South Carolina, Charleston, SC. 4. Department of Clinical Pharmacy & Outcome Sciences, Medical University of South Carolina, Charleston, SC.
Abstract
OBJECTIVE: To determine the pharmacokinetics (PK) and placental transfer of intravenous (i.v.) N-acetylcysteine (NAC) in mothers with a clinical diagnosis of chorioamnionitis (CA) and determine the PK of i.v. NAC in their infants. STUDY DESIGN: In this prospective, double-blind study i.v. NAC 100 mg/kg/dose or saline was administered within 4 hours of CA diagnosis to pregnant women ≥24 weeks' gestation and then every 6 hours until delivery. Maternal PK and placental transfer were determined with maternal blood and matched maternal and cord venous blood. Neonatal PK estimates were determined from i.v. NAC (12.5-25 mg/kg/dose) administered every 12 hours for 5 doses. Noncompartmental analyses were performed for maternal and neonatal PK estimates. RESULTS:Eleven mothers (5 preterm, 6 near-term) and 12 infants (1 set of twins) receivedNAC. Maternal clearance (CL) of NAC was faster than in nonpregnant adults, with a terminal elimination half-life of 1.2 ± 0.2 hours. The NAC cord to maternal ratio was 1.4 ± 0.8, suggesting rapid placental transfer and slower rate of fetal CL. Neonatal PK estimates for near-term compared with preterm infants showed a significantly shorter terminal elimination half-life (5.1 vs 7.5 hours, respectively) and greater CL (53.7 vs 45.0 mL/h/kg, respectively). CONCLUSIONS:Maternal CL and placental transfer of NAC was rapid, with umbilical cord concentrations frequently exceeding maternal concentrations. The administration of NAC to mothers with CA achieves predictable NAC plasma concentrations in the fetus, indicating that antenatal neuroprotection may be possible for these newborns at high risk for neuroinflammation.
RCT Entities:
OBJECTIVE: To determine the pharmacokinetics (PK) and placental transfer of intravenous (i.v.) N-acetylcysteine (NAC) in mothers with a clinical diagnosis of chorioamnionitis (CA) and determine the PK of i.v. NAC in their infants. STUDY DESIGN: In this prospective, double-blind study i.v. NAC 100 mg/kg/dose or saline was administered within 4 hours of CA diagnosis to pregnant women ≥24 weeks' gestation and then every 6 hours until delivery. Maternal PK and placental transfer were determined with maternal blood and matched maternal and cord venous blood. Neonatal PK estimates were determined from i.v. NAC (12.5-25 mg/kg/dose) administered every 12 hours for 5 doses. Noncompartmental analyses were performed for maternal and neonatal PK estimates. RESULTS: Eleven mothers (5 preterm, 6 near-term) and 12 infants (1 set of twins) received NAC. Maternal clearance (CL) of NAC was faster than in nonpregnant adults, with a terminal elimination half-life of 1.2 ± 0.2 hours. The NAC cord to maternal ratio was 1.4 ± 0.8, suggesting rapid placental transfer and slower rate of fetal CL. Neonatal PK estimates for near-term compared with preterm infants showed a significantly shorter terminal elimination half-life (5.1 vs 7.5 hours, respectively) and greater CL (53.7 vs 45.0 mL/h/kg, respectively). CONCLUSIONS: Maternal CL and placental transfer of NAC was rapid, with umbilical cord concentrations frequently exceeding maternal concentrations. The administration of NAC to mothers with CA achieves predictable NAC plasma concentrations in the fetus, indicating that antenatal neuroprotection may be possible for these newborns at high risk for neuroinflammation.
Authors: Manjeet K Paintlia; Ajaib S Paintlia; Miguel A Contreras; Inderjit Singh; Avtar K Singh Journal: Exp Neurol Date: 2007-12-23 Impact factor: 5.330
Authors: Henry L Galan; Anna Maria Marconi; Cinzia L Paolini; Alex Cheung; Frederick C Battaglia Journal: Am J Obstet Gynecol Date: 2008-11-18 Impact factor: 8.661
Authors: Elizabeth Nance; Michael Porambo; Fan Zhang; Manoj K Mishra; Markus Buelow; Rachel Getzenberg; Michael Johnston; Rangaramanujam M Kannan; Ali Fatemi; Sujatha Kannan Journal: J Control Release Date: 2015-07-13 Impact factor: 9.776
Authors: Robert S B Clark; Philip E Empey; Hülya Bayır; Bedda L Rosario; Samuel M Poloyac; Patrick M Kochanek; Thomas D Nolin; Alicia K Au; Christopher M Horvat; Stephen R Wisniewski; Michael J Bell Journal: PLoS One Date: 2017-07-07 Impact factor: 3.240
Authors: Dorothea D Jenkins; Donald B Wiest; Denise M Mulvihill; Anthony M Hlavacek; Sarah J Majstoravich; Truman R Brown; Joseph J Taylor; Jason R Buckley; Robert P Turner; Laura Grace Rollins; Jessica P Bentzley; Kathryn E Hope; Andrew B Barbour; Danielle W Lowe; Renee H Martin; Eugene Y Chang Journal: J Pediatr Date: 2015-11-03 Impact factor: 4.406