Teratogenic effect of diphenylhydantoin and/or fluphenazine in mice

Diphenylhydantoin and fluphenazine are two drugs that act on the central nervous system. Many patients are taking these two drugs together and sometimes during pregnancy. Therefore, this study was conducted to determine the safety or the teratogenic effect of these two drugs alone or in combination. Pregnant mice were administered diphenylhydantoin at 50 mg kg-1 body wt. and/or fluphenazine at 1 mg kg-1 body wt. by gavage. The control group was administered the vehicle of diphenylhydantoin (water containing 0.6% alcohol). All pregnant animals were treated from day 6 to day 15 of gestation. The females were sacrificed on day 18. A significant reduction of fetal weight and length was found in all treatment groups when compared to the control. As regards to skeletal anomalies, it was found that the incidence of incomplete ossification of sternebrae and skull bones was significantly increased in the combination group when compared to the control group. Examination of visceral anomalies showed that dilated cerebral ventricles were observed in the fluphenazine-treated group, with the incidence of these malformations increasing significantly when diphenylhydantoin was administered in combination with fluphenazine. In summary, the administration of diphenylhydantoin and fluphenazine in combination was shown to be more teratogenic than each drug alone.