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母体给予依那普利对大鼠胎儿发育的影响。

The effect of maternal administration of enalapril on fetal development in the rat.

作者信息

al-Harbi M M, al-Shabanah O A, al-Gharably N M, Islam M W

机构信息

Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

出版信息

Res Commun Chem Pathol Pharmacol. 1992 Sep;77(3):347-58.

PMID:1455073
Abstract

Enalapril (MK, 421), an angiotensin converting enzyme inhibitor, was tested for teratogenicity using Wistar rats. The drug was given by oral intubation, from 6-15 days of gestation, at the doses of 0, 3, 10 and 30 mg/kg/day. Reduction in body weight and food consumption were observed in the treated dams. However, food efficiency index, assessed at different periods of gestation was found to be unaffected. On day 20 of gestation, all the dams were sacrificed by cervical dislocation and sign of maternal toxicity, reproduction indices and fetal measures were recorded. The dams treated with enalapril at only the doses of 10 and 30 mg/kg, produced significant decrease in numbers of implants, litter size and incidence of reabsorbed fetuses, and also reduced neonatal growth. No such effects were observed at the lowest dose level (3 mg/kg) used. External, visceral and skeletal examinations of the fetuses of enalapril-treated dams showed several types of variations in all groups, but no consistent pattern were observed. However, a slight increase in skeletal variations was seen with the highest dose (30 mg/kg) group. The data of the present study under the conditions described herein and at the doses employed, revealed no evidence of teratogenesis, but numerous deleterious effects on the fetus were evident.

摘要

依那普利(MK,421)是一种血管紧张素转换酶抑制剂,使用Wistar大鼠对其进行致畸性测试。在妊娠第6至15天,通过口服插管给予该药物,剂量分别为0、3、10和30毫克/千克/天。在接受治疗的母鼠中观察到体重减轻和食物摄入量减少。然而,发现妊娠不同时期评估的食物效率指数未受影响。在妊娠第20天,通过颈椎脱臼处死所有母鼠,并记录母体毒性迹象、生殖指数和胎儿测量数据。仅用10和30毫克/千克剂量依那普利治疗的母鼠,着床数、窝仔数和吸收胎儿的发生率显著降低,并且新生儿生长也受到抑制。在使用的最低剂量水平(3毫克/千克)未观察到此类影响。对接受依那普利治疗的母鼠所产胎儿进行的外观、内脏和骨骼检查显示,所有组均有几种类型的变异,但未观察到一致的模式。然而,最高剂量(30毫克/千克)组的骨骼变异略有增加。在本文所述条件下和所采用剂量下的本研究数据显示,没有致畸证据,但对胎儿有许多有害影响是明显的。

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