title: Antenatal pharmacokinetics and placental transfer of N-acetylcysteine in chorioamnionitis for fetal neuroprotection.
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.
  
  
  METHODS
  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: Department of Clinical Pharmacy & Outcome Sciences, Medical University of South Carolina, Charleston, SC. Electronic address: wiestdb@musc.edu.
authors: Donald B
authors: DB
authors: Wiest
authors: Department of Obstetrics & Gynecology, Medical University of South Carolina, Charleston, SC.
authors: Eugene
authors: E
authors: Chang
authors: Department of Pediatrics, Medical University of South Carolina, Charleston, SC.
authors: Deanna
authors: D
authors: Fanning
authors: Department of Clinical Pharmacy & Outcome Sciences, Medical University of South Carolina, Charleston, SC.
authors: Sandra
authors: S
authors: Garner
authors: Department of Clinical Pharmacy & Outcome Sciences, Medical University of South Carolina, Charleston, SC.
authors: Toby
authors: T
authors: Cox
authors: Department of Pediatrics, Medical University of South Carolina, Charleston, SC.
authors: Dorothea D
authors: DD
authors: Jenkins
mesh_terms: D000111:Acetylcysteine / Q000493:pharmacokinetics*; D002821:Chorioamnionitis / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005312:Fetal Blood / Q000187:drug effects; D016166:Free Radical Scavengers / Q000493:pharmacokinetics; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D007262:Infusions, Intravenous; D008297:Male; D008431:Maternal-Fetal Exchange; D009035:Mothers; D018696:Neuroprotective Agents / Q000493:pharmacokinetics*; D010865:Pilot Projects; D010920:Placenta / Q000187:drug effects*; D011247:Pregnancy; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D000111:Acetylcysteine