Kamada S, Sakanoue M, Takeuchi M, Shimpo K, Tanabe T
J Toxicol Sci. 1984 Jun;9 Suppl 1:53-72. doi: 10.2131/jts.9.supplementi_53.
The effects of ranitidine hydrochloride, a histamine H2-receptor antagonist, on delivery, lactation, postnatal development of F1 generation of Crj:CD (SD) rats were examined. Ranitidine hydrochloride was intravenously administered once daily from day 17 of gestation to day 21 after delivery at dose levels of 5, 15 and 40 mg/kg in base weight respectively. All females were allowed to litter naturally, and postnatal development of offsprings was observed. Tachypnea, prone position and transient tremor were observed for approximately one minute directly after an intravenous administration of ranitidine in the dose of 40 mg/kg, which were probably induced by a rapid fall in blood pressure. In delivery and postpartum observation, there occurred no influence of the ranitidine administration on maternal body weight, delivery and lactation. In studies on general behavior of F1 rats, no abnormal changes were observed on postnatal development and various functions such as reflex response and learning. Ranitidine treatment did not affect reproductive performances of F1 generation. A slight inhibition in body weight gain and a slight decrease in average weight of liver were observed in F1 females of 40 mg/kg group, but no other influence attributable to the ranitidine administration was observed on the general state and development of offsprings. In necropsy of offsprings, hydronephrosis, transitional epithelial carcinoma, kinky tail, unilateral absence of testis and epididymis were observed in one case of ranitidine-treated groups. But they were not attributable to administration of ranitidine. In summary, it was concluded that ranitidine hydrochloride had no effects on delivery and lactation of dams, and also on viability, development and various functions of F1 generation at the dose of 40 mg/kg/day or less.
研究了组胺H2受体拮抗剂盐酸雷尼替丁对Crj:CD(SD)大鼠F1代分娩、泌乳及产后发育的影响。从妊娠第17天至产后第21天,分别以5、15和40mg/kg体重的剂量水平每日静脉注射一次盐酸雷尼替丁。所有雌性大鼠均自然产仔,并观察后代的产后发育情况。静脉注射40mg/kg剂量的雷尼替丁后,直接观察到约一分钟的呼吸急促、俯卧位和短暂震颤,这可能是由血压快速下降引起的。在分娩和产后观察中,雷尼替丁的给药对母体体重、分娩和泌乳没有影响。在对F1大鼠的一般行为研究中,未观察到产后发育以及反射反应和学习等各种功能的异常变化。雷尼替丁治疗不影响F1代的生殖性能。在40mg/kg组的F1雌性大鼠中观察到体重增加略有抑制,肝脏平均重量略有下降,但未观察到雷尼替丁给药对后代的一般状态和发育有其他影响。在对后代的尸检中,在雷尼替丁治疗组的一例中观察到肾盂积水、移行上皮癌、卷尾、单侧睾丸和附睾缺失,但这些并非由雷尼替丁给药所致。总之,得出的结论是,盐酸雷尼替丁在剂量为40mg/kg/天或更低时,对母鼠的分娩和泌乳以及F1代的活力、发育和各种功能均无影响。