Preclinical toxicology studies with the angiotensin-converting enzyme inhibitor quinapril hydrochloride (Accupril).
Acute, subacute, and chronic toxicity studies, carcinogenicity bioassays, and reproductive and genetic toxicology studies were performed with quinapril, an ACE inhibitor used in the treatment of hypertension. Acute toxicity is minimal in rodents, and repeated dosing elicits gastric irritation, juxtaglomerular apparatus (JGA) hypertrophy and hyperplasia and tubular degenerative changes in the kidney, and reduced red cell parameters and heart weights in rodents and/or dogs. Other manifestations of toxicity, including hepatic lesions in dogs, reduced offspring weights in rats, marked sensitivity of the rabbit, and clastogenic effects at cytotoxic doses in the in vitro V79 chromosome aberration assay, have been reported with other drugs of this class.
McGuire
E J
EJ
Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, Michigan 48105, USA.
Anderson
J A
JA
Gough
A W
AW
Herman
J R
JR
Pegg
D G
DG
Theiss
J C
JC
de la Iglesia
F A
FA
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000633:toxicity*; D000818:Animals; D000959:Antihypertensive Agents / Q000633:toxicity*; D015197:Carcinogenicity Tests; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D005260:Female; D007546:Isoquinolines / Q000633:toxicity*; D008297:Male; D011355:Prodrugs / Q000633:toxicity*; D000077583:Quinapril; D012098:Reproduction / Q000187:drug effects; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007546:Isoquinolines; D011355:Prodrugs; D044005:Tetrahydroisoquinolines; D000077583:Quinapril