Acute, subchronic and chronic toxicity of the new angiotensin converting enzyme inhibitor ramipril.
Acute, subchronic and chronic toxicity studies of 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S, 3S, 5S)-2-azabicyclo[3.3.0]octane-3-carboxylic acid (ramipril, Hoe 498) were conducted in mice, rats, dogs and monkeys. The acute toxicity in mice, rats, and dogs after oral and intravenous administration is very low. There were no significant differences in LD50 values between male and female animals. Treatment periods up to 6 months in rats and monkeys and up to 12 months in dogs revealed consistent compound-related effects with respect to the kidneys and the hemopoietic system probably due to exaggerated pharmacological activity. Species-specific lesions in the gastric fundal mucosa were noted exclusively in rats. No adverse effects were seen at doses of 0.25 mg/kg/d in rats, 2.5 mg/kg/d in dogs, and 0.5 mg/kg/d in monkeys. It is concluded that ramipril can be safely used in humans.
Donaubauer
H H
HH
Department of Toxicology and Pathology, Hoechst Aktiengesellschaft, Frankfurt/Main, Fed. Rep. of Germany.
Mayer
D
D
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000633:toxicity*; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000633:toxicity*; D001952:Bridged-Ring Compounds / Q000633:toxicity*; D004285:Dogs; D005753:Gastric Mucosa / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology; D007928:Lethal Dose 50; D008253:Macaca mulatta; D051379:Mice; D008813:Mice, Inbred ICR; D017257:Ramipril; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D017257:Ramipril