Fertility and perinatal/postnatal studies in rats with the angiotensin-converting enzyme inhibitor, quinapril.
Quinapril, an inhibitor of angiotensin-converting enzyme (ACE) and an antihypertensive agent, was evaluated in rats for effects on fertility, reproduction, and perinatal and postnatal development. In a fertility study, male rats were treated by gavage for 60 days prior to and during mating and female rats were treated by gavage for 14 days prior to mating, during mating and gestation, and during lactation with doses of 0, 10, 50, or 100 mg quinapril/kg body wt. There were no significant effects on body weight, food consumption, fertility indices, fetal development, or neonatal growth, survival, development, behavior, or reproduction. In a perinatal/postnatal study, administration of quinapril to females at doses of 25, 75, or 150 mg/kg during late gestation and lactation had no effects on parturition, lactation, or postnatal development, but a significant decrease in neonatal body weight during the suckling period was observed at all doses. In a subsequent study, female rats were given 150 mg/kg during late gestation, lactation, or late gestation and lactation. No adverse effects were seen in the dams or the offspring, and no reduction in neonatal body weight was observed. Kidneys from pups whose mothers received quinapril during gestation and/or lactation had minimal juxtaglomerular cell hypertrophy, characteristic of treatment with ACE inhibitors. Low levels of quinaprilat (the major and pharmacologically active metabolite of quinapril) were detected in fetal blood and in neonatal blood, indicating offspring exposure to quinapril. Milk quinaprilat concentrations were 3-5% of the plasma concentrations 3-5 hr after dosing. These studies demonstrate no adverse effects of quinapril on fertility, reproduction, or perinatal and postnatal development.
Dostal
L A
LA
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Kim
S N
SN
Schardein
J L
JL
Anderson
J A
JA
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005298:Fertility / Q000187:drug effects*; D006128:Growth / Q000187:drug effects*; D007546:Isoquinolines / Q000493:pharmacokinetics / Q000633:toxicity*; D007668:Kidney / Q000473:pathology; D007774:Lactation / Q000187:drug effects; D008297:Male; D008431:Maternal-Fetal Exchange; D008892:Milk / Q000378:metabolism; D011247:Pregnancy; D000077583:Quinapril; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects; D012098:Reproduction / Q000187:drug effects; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D000077583:Quinapril