The effect of maternal administration of enalapril on fetal development in the rat.
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.
al-Harbi
M M
MM
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
al-Shabanah
O A
OA
al-Gharably
N M
NM
Islam
M W
MW
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D004656:Enalapril / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D008297:Male; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D004656:Enalapril