Placental transfer of vigabatrin (gamma-vinyl GABA) and its effect on concentration of amino acids in the embryo of TO mice.
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.
Department of Paediatrics, FMHS, United Arab Emirates University, PO Box 17666, Al Ain, United Arab Emirates. yousef@uaeu.ac.ae
Y M
YM
Abdulrazzaq
R
R
Padmanabhan
S M
SM
Bastaki
A
A
Ibrahim
A
A
Bener
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D004622:Embryo, Mammalian / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D008297:Male; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange / Q000187:drug effects*; D051379:Mice; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020888:Vigabatrin / Q000493:pharmacokinetics / Q000633:toxicity*
D000596:Amino Acids; D004791:Enzyme Inhibitors; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin