Toxicity studies of the non-sulfhydryl angiotensin converting enzyme inhibitor N-[8-amino-1(S)-carboxyoctyl]-L-alanyl-L-proline in rats.
The acute and subacute toxicities of N-[8-amino-1(S)-carboxyoctyl]-L- alanyl-L-proline (AB-47, CAS 120008-53-9), which is a non-sulfhydryl angiotensin converting enzyme inhibitor, were studied in male and female Fischer 344 rats. In the acute study, male and female rats were orally given 5000 mg/kg of AB-47. No rats were dead during the observation period (14 days) after the administration. The LD50 values of AB-47 were more than 5000 mg/kg in both male and female rats. Although only diarrhoea as toxic sign was observed 2 to 7 h after the administration, this sign disappeared within 24 h after the administration. Necropsy at the termination of observations revealed no macroscopic lesions in any rats. In the subacute study, male and female Fischer 344 rats were orally given 40, 200 or 1000 mg/kg/d of AB-47 for 4 weeks. Neither toxic signs nor death due to drug effects were observed at any dosage levels of AB-47. Furthermore, AB-47 did not influence body weight, food consumption, food efficiency, urinalytical and hematological parameters in both male and female rats. The minor changes of serum parameters, which consisted of very slight increases in serum potassium and decreases in serum albumin/globulin ratio, occurred in male rats given 200 and 1000 mg/kg/d of AB-47. Serum urea nitrogen values were elevated in both male and female rats given 1000 mg/kg/d of AB-47. Slight decreases of heart weight and heart weight/body weight ratios were observed at all dosage levels of AB-47.(ABSTRACT TRUNCATED AT 250 WORDS)
Shirota
M
M
Central Research Laboratories, Asahi Breweries, Ltd., Tokyo, Japan.
Inoue
H
H
Yamamoto
T
T
Kajiwara
Y
Y
Kitabatake
K
K
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000633:toxicity*; D000818:Animals; D001772:Blood Cell Count; D001797:Blood Protein Electrophoresis; D001835:Body Weight / Q000187:drug effects; D004151:Dipeptides / Q000633:toxicity*; D004435:Eating / Q000187:drug effects; D005260:Female; D007928:Lethal Dose 50; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011188:Potassium / Q000097:blood; D051381:Rats; D011916:Rats, Inbred F344
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; C065126:N-(8-amino-1-carboxyoctyl)-alanyl-proline; D011188:Potassium