Document Detail

Transplacental transport of N-acetylcysteine in an ovine model.
MedLine Citation:
PMID:  1928876     Owner:  NLM     Status:  MEDLINE    
STUDY OBJECTIVE: Acetaminophen freely crosses the placenta, and acetaminophen ingestion is the most frequent intentional overdose in pregnancy. Although most patients do well after maternal treatment with the antidote N-acetylcysteine (NAC), fetal death with massive hepatic necrosis has occurred. It has never been shown whether NAC crosses the placenta to yield fetal plasma levels equal to those associated with hepatoprotective effects in human beings. Our study objective was to evaluate this in a widely accepted large animal model for maternal-fetal research. DESIGN AND TYPE OF PARTICIPANTS: A nonblinded experiment was performed using four domestic sheep at near-term gestation. INTERVENTIONS: NAC 150 mg/kg IV was administered to the ewe over 15 minutes. After induction of anesthesia, the fetal head was delivered surgically and a neck vein cannulated for blood sampling. Maternal and fetal blood samples were obtained at the end of NAC infusion, at 30- and then at 60-minute intervals for four hours. Plasma NAC levels were determined by gas chromatography/mass spectroscopy (detection limit, 2 micrograms/mL; quantification limit, 5 micrograms/mL). RESULTS: Maternal peak plasma NAC levels were 619, 631, 1,757, and 2,512, micrograms/mL, respectively, within 30 minutes of infusion. However, NAC was only minimally detectable in plasma of two fetal animals and transiently reached quantifiable levels in two others. None of the fetal animals attained serial plasma NAC levels that equalled those associated with therapeutic dosing or hepatoprotective effects in human beings. CONCLUSION: Transplacental transport of NAC is clinically insignificant in a mammalian model resembling the human being. These findings suggest that the human fetal liver is not protected from acetaminophen toxicity by maternal NAC therapy.
B S Selden; S C Curry; R F Clark; B C Johnson; R Meinhart; V B Pizziconi
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Annals of emergency medicine     Volume:  20     ISSN:  0196-0644     ISO Abbreviation:  Ann Emerg Med     Publication Date:  1991 Oct 
Date Detail:
Created Date:  1991-11-13     Completed Date:  1991-11-13     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  8002646     Medline TA:  Ann Emerg Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1069-72     Citation Subset:  AIM; IM    
Department of Medical Toxicology, Good Samaritan Regional Medical Center, Phoenix, Arizona.
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MeSH Terms
Acetylcysteine / blood,  metabolism*
Fetal Blood
Infusions, Intravenous
Maternal-Fetal Exchange*
Models, Biological
Reg. No./Substance:

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