Miyamoto M, Otsu M, Sugisaki T, Sakaguchi T
Nihon Yakurigaku Zasshi. 1975 May;71(4):367-78.
A41 304 at 400 mug/kg produced depression of body weight gains in the rat dams but did not increase the number of the fetuses with gross malformations. At 400 mug/kg of dexamethasone, body weight gains of the rat dams were markedly depressed and fetuses presented cleft palate and depression of the placental weight, body weight and crown-rump length. As for the influence of both drugs upon the fetal skeleton, ossification of the odontoid process and metatarsus was delayed and lumbar ribs increased. Dexamethasone at 400 mug/kg, in addition to these findings, caused prominently delayed ossification to the caudal vertebrae. When A41 304 at 1600 mug/kg and dexamethasone at 400 mug/kg were given to pregnant mice, cleft palate occurred with high incidences, but neither visceral abnormalities nor skeletal malformations attributable to the drug administration were observed. The critical period of cleft palate which was noted in the mice given A41 304 was day 11 through day 15 of pregnancy, mainly 11 approximately 13 of pregnancy. Cleft palate was seen in a dose-related manner in either A41 304-treated groups or dexamethasone-treated groups, but the incidence at the same dosage level was higher in dexamethasome-treated groups than in A41 304-treated groups.
大鼠母体以400微克/千克的剂量给予A41 304会导致体重增加受抑制,但并未增加严重畸形胎儿的数量。以400微克/千克的剂量给予地塞米松时,大鼠母体的体重增加明显受抑制,胎儿出现腭裂,胎盘重量、体重和顶臀长度均降低。至于这两种药物对胎儿骨骼的影响,齿突和跖骨的骨化延迟,腰椎肋骨增多。除了这些结果外,400微克/千克的地塞米松还导致尾椎骨化明显延迟。给怀孕小鼠以1600微克/千克的剂量给予A41 304和以400微克/千克的剂量给予地塞米松时,腭裂发生率很高,但未观察到因给药导致的内脏异常或骨骼畸形。在给予A41 304的小鼠中观察到的腭裂关键期为妊娠第11天至第15天,主要是妊娠第11天至第13天。在A41 304处理组或地塞米松处理组中,腭裂均呈剂量相关方式出现,但在相同剂量水平下,地塞米松处理组的发生率高于A41 304处理组。