Ballard P D, Hearney E F, Smith M B
Teratology. 1977 Oct;16(2):175-80. doi: 10.1002/tera.1420160211.
Three glucocorticoids (dexamethasone, hydrocortisone, and prednisolone), were ocularly applied to pregnant CD-1 mice on days 10-13 of gestation. The drug concentrations were various multiples of the common therapeutic dose levels and were applied to both eyes in 1 microliter drops five times a day. Eighteen-day fetuses were examined for malformations. A significant increase in the incidence of cleft palate was observed in fetuses treated with each of these glucocorticoids. There appeared to be a dose related effect on cleft palate width among fetuses from both dexamethasone and prednisolone treated dams. The incidence of sex organ anomalies, although lower than the incidence of cleft palate, also showed a positive dose relationship. Analysis of variance was used to compare the teratogenic effects of these glucocorticoids ocularly applied in equipotent anti-inflammatory concentrations. Our results indicate that dexamethasone produces a higher incidence of cleft palate, than either of the other two drugs when given in equipotent concentrations. It appears that the teratogenic potency of these ocularly applied glucocorticoids cannot be predicted on the basis of anti-inflammatory potency.
在妊娠第10至13天,对怀孕的CD-1小鼠眼部应用三种糖皮质激素(地塞米松、氢化可的松和泼尼松龙)。药物浓度为常用治疗剂量水平的不同倍数,每天分五次以1微升滴眼液的形式滴入双眼。对18日龄的胎儿进行畸形检查。在用这些糖皮质激素中的每一种治疗的胎儿中,观察到腭裂发生率显著增加。在地塞米松和泼尼松龙处理的母鼠所产胎儿中,腭裂宽度似乎存在剂量相关效应。性器官异常的发生率虽然低于腭裂发生率,但也呈现出正剂量关系。采用方差分析比较这些以等效抗炎浓度眼部应用的糖皮质激素的致畸作用。我们的结果表明,当以等效浓度给药时,地塞米松导致腭裂的发生率高于其他两种药物中的任何一种。看来,这些眼部应用的糖皮质激素的致畸效力不能根据抗炎效力来预测。