Abdel-Hamid H A, Abdel-Rahman M S, Abdel-Rahman S A
Department of Pharmacology and Toxicology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, USA.
J Appl Toxicol. 1996 May-Jun;16(3):221-5. doi: 10.1002/(SICI)1099-1263(199605)16:3<221::AID-JAT336>3.0.CO;2-Q.
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.
苯妥英和氟奋乃静是两种作用于中枢神经系统的药物。许多患者同时服用这两种药物，有时在孕期也会服用。因此，开展本研究以确定这两种药物单独使用或联合使用时的安全性或致畸作用。通过灌胃给怀孕小鼠按50毫克/千克体重给予苯妥英和/或按1毫克/千克体重给予氟奋乃静。对照组给予苯妥英的赋形剂（含0.6%酒精的水）。所有怀孕动物在妊娠第6天至第15天接受处理。在第18天处死雌性小鼠。与对照组相比，所有处理组的胎儿体重和长度均显著降低。关于骨骼异常，发现联合用药组与对照组相比，胸骨和颅骨不完全骨化的发生率显著增加。内脏异常检查显示，氟奋乃静处理组观察到脑室扩张，当苯妥英与氟奋乃静联合使用时，这些畸形的发生率显著增加。总之，与单独使用每种药物相比，苯妥英和氟奋乃静联合使用显示出更强的致畸性。
