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 unkn own. 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 adminis tered intraperitoneally to a group of Theiler outbred (TO) mice on gestatio nal day (GD) 10. The controls received a proportionate volume of saline. Ma ternal blood samples, embryos, and placentas were collected at 3.5, 6.0, an d 9.0 hr after treatment and their total amino acid concentrations determin ed in an ion-exchange amino acid analyzer. Results: At 3.5 hr, there was a decrease in concentrations of some amino ac ids in the blood, placenta, and embryos of VGB-treated mice, but the decrea se in methionine was most marked, gamma -aminobutyric acid (GABA) was signi ficantly 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. Vigabatri n 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 ver y 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 af ter 3.5 hr in the placenta and embryo. Methionine concentration is most sev erely affected in VGB treated mothers, placentas, and fetuses. We speculate that this deficiency could be a possible mechanism for the teratogenic eff ects of vigabatrin.