Transplacental transfer and biotransformation studies of valproic acid and its glucuronide(s) in the perfused human placenta

Fowler D.W., Eadie M.J. and Dickinson R.G. (1989) Transplacental transfer and biotransformation studies of valproic acid and its glucuronide(s) in the perfused human placenta. Journal of Pharmacology and Experimental Therapeutics, 249 1: 318-323.

Author Fowler D.W.
Eadie M.J.
Dickinson R.G.
Title Transplacental transfer and biotransformation studies of valproic acid and its glucuronide(s) in the perfused human placenta
Journal name Journal of Pharmacology and Experimental Therapeutics   Check publisher's open access policy
ISSN 0022-3565
Publication date 1989-01-01
Sub-type Article (original research)
Open Access Status Not yet assessed
Volume 249
Issue 1
Start page 318
End page 323
Total pages 6
Language eng
Subject 3004 Pharmacology
Abstract 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Scopus Import - Archived
 
Versions
Version Filter Type
Citation counts: Scopus Citation Count Cited 26 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 12 Jul 2016, 11:09:45 EST by System User