PMID- 11283969
OWN - NLM
STAT- MEDLINE
DCOM- 20010607
LR  - 20131121
IS  - 0040-3709 (Print)
IS  - 0040-3709 (Linking)
VI  - 63
IP  - 3
DP  - 2001 Mar
TI  - Placental transfer of vigabatrin (gamma-vinyl GABA) and its effect on 
      concentration of amino acids in the embryo of TO mice.
PG  - 127-33
AB  - BACKGROUND: The mechanism of the teratogenicity of vigabatrin (VGB) is unknown. 
      The objectives of this study were to determine the placental transfer of VGB and 
      to evaluate the effect of VGB on maternal, placental, and fetal concentrations of 
      amino acids. METHODS: A single dose of 400 mg/kg VGB in physiological saline was 
      administered intraperitoneally to a group of Theiler outbred (TO) mice on 
      gestational day (GD) 10. The controls received a proportionate volume of saline. 
      Maternal blood samples, embryos, and placentas were collected at 3.5, 6.0, and 
      9.0 hr after treatment and their total amino acid concentrations determined in an 
      ion-exchange amino acid analyzer. RESULTS: At 3.5 hr, there was a decrease in 
      concentrations of some amino acids in the blood, placenta, and embryos of 
      VGB-treated mice, but the decrease in methionine was most marked. 
      gamma-aminobutyric acid (GABA) was significantly higher in the VGB group in both 
      the embryos and the placentas at 3.5 hr but at 6.0 and 9.0 hr the differences 
      were not significant. Vigabatrin levels were higher in the placenta than in the 
      embryo at 3.5 hr, but at 6.0 hr there was an overlap of the VGB peak with that of 
      tryptophan with very much lower levels than at 3.5 hr. At 9.0 hr, there was no 
      vigabatrin peak in either the placenta or the embryo. CONCLUSIONS: Maternal 
      exposure to VGB results in peak levels of the drug after 3.5 hr in the placenta 
      and embryo. Methionine concentration is most severely affected in VGB-treated 
      mothers, placentas, and fetuses. We speculate that this deficiency could be a 
      possible mechanism for the teratogenic effects of vigabatrin.
CI  - Copyright 2001 Wiley-Liss, Inc.
FAU - Abdulrazzaq, Y M
AU  - Abdulrazzaq YM
AD  - Department of Paediatrics, FMHS, United Arab Emirates University, PO Box 17666, 
      Al Ain, United Arab Emirates. yousef@uaeu.ac.ae
FAU - Padmanabhan, R
AU  - Padmanabhan R
FAU - Bastaki, S M
AU  - Bastaki SM
FAU - Ibrahim, A
AU  - Ibrahim A
FAU - Bener, A
AU  - Bener A
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Teratology
JT  - Teratology
JID - 0153257
RN  - 0 (Amino Acids)
RN  - 0 (Enzyme Inhibitors)
RN  - EC 2.6.1.19 (4-Aminobutyrate Transaminase)
RN  - GR120KRT6K (Vigabatrin)
SB  - IM
MH  - 4-Aminobutyrate Transaminase/antagonists & inhibitors
MH  - Amino Acids/*metabolism
MH  - Animals
MH  - Embryo, Mammalian/*metabolism
MH  - Enzyme Inhibitors/pharmacokinetics/*toxicity
MH  - Female
MH  - Male
MH  - Maternal Exposure
MH  - Maternal-Fetal Exchange/*drug effects
MH  - Mice
MH  - Placenta/*metabolism
MH  - Pregnancy
MH  - Pregnancy, Animal/blood/*drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Vigabatrin/pharmacokinetics/*toxicity
EDAT- 2001/04/03 10:00
MHDA- 2001/06/19 10:01
CRDT- 2001/04/03 10:00
PHST- 2001/04/03 10:00 [pubmed]
PHST- 2001/06/19 10:01 [medline]
PHST- 2001/04/03 10:00 [entrez]
AID - 10.1002/tera.1023 [pii]
AID - 10.1002/tera.1023 [doi]
PST - ppublish
SO  - Teratology. 2001 Mar;63(3):127-33. doi: 10.1002/tera.1023.