TERATOGENIC EFFECT OF DIPHENYLHYDANTOIN AND OR FLUPHENAZINE IN MICE/

Diphenylhydantoin and fluphenazine are two drugs that act on the centr al nervous system, Many patients are taking these two drugs together a nd sometimes during pregnancy, Therefore, this study was conducted to determine the safety or the teratogenic effect of these two drugs alon e 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 diphenylh ydantoin (water containing 0.6% alcohol), All pregnant animals were tr eated from day 6 to day 15 of gestation, The females were sacrificed o n day 18, A significant reduction of fetal weight and length was found in all treatment groups when compared to the control, As regards to s keletal anomalies, it was found that the incidence of incomplete ossif ication of sternebrae and skull bones was significantly increased in t he combination group when compared to the control group, Examination o f visceral anomalies showed that dilated cerebral ventricles were obse rved in the fluphenazine-treated group, with the incidence of these ma lformations increasing significantly when diphenylhydantoin was admini stered in combination with fluphenazine, In summary, the administratio n of diphenylhydantoin and fluphenazine in combination was shown to he more teratogenic than each drug alone.