Document Detail


Transplacental transfer and biotransformation studies of valproic acid and its glucuronide(s) in the perfused human placenta.
MedLine Citation:
PMID:  2496226     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Transplacental transfer and biotransformation of valproic acid (VPA) and its acyl glucuronide conjugate (VPA-G) were investigated in the isolated perfused term human placenta. In peripheral lobules perfused under dual (maternal and fetal) recirculation for 6 hr, VPA was readily transferred, reaching equilibrium (stable maternal and fetal VPA concentrations with no transplacental gradient of unbound VPA) within 1.5 hr. Metabolism of VPA was not detected. VPA-G was transferred more slowly. After 6 hr of dual recirculation, equilibrium had not been reached and VPA-G had undergone extensive hydrolysis to VPA (34%) and rearrangement via acyl migration to structural isomers (collectively VPA-GR, 9%). Hydrolysis of VPA-G occurred, at least in part, in the perfusates contaminated with placental blood and/or with enzymes leached from placental tissue. Reliable transfer data for VPA-G were obtained using the dual single pass perfusion method. Steady state was achieved within 15 min and VPA, VPA-G and VPA-GR were transferred from maternal to fetal perfusates at 95, 13 and 17%, respectively, of antipyrine clearance. Transfer was positively correlated with lipophilicity as measured by the logarithm of the octanol/water partition coefficient: 0.204, -1.85, -1.66 for VPA, VPA-G and VPA-GR, respectively.
Authors:
D W Fowler; M J Eadie; R G Dickinson
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  249     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1989 Apr 
Date Detail:
Created Date:  1989-06-01     Completed Date:  1989-06-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  318-23     Citation Subset:  IM    
Affiliation:
Department of Medicine University of Queensland, Royal Brisbane Hospital, Australia.
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MeSH Terms
Descriptor/Qualifier:
Biotransformation
Female
Humans
Metabolic Clearance Rate
Perfusion
Placenta / metabolism*
Pregnancy
Solubility
Valproic Acid / analogs & derivatives*,  pharmacokinetics*
Chemical
Reg. No./Substance:
60113-83-9/valproic acid glucuronide; 99-66-1/Valproic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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