Thirteen-week repeated oral dose toxicity study of ecabapide, a gastroprokinetic drug, in dogs and rats.
Thirteen-week oral repeated dose toxicity of ecabapide, a gastroprokinetic drug, was investigated in dogs at dosage levels of 50, 175 or 600 mg/kg, and in rats at dosage levels of 25, 100, 400 or 1600 mg/kg. In dogs, vomiting, aqueous salivation, body weight gain inhibition, and hemolytic anemia, together with an increase in Heinz body formation, were observed at 175 and/or 600 mg/kg. Histological examination revealed enhanced hemosiderin deposition in the liver and spleen, retention of erythrocytes in the splenic sinus and enhanced erythropoiesis in bone marrow at 175 and/or 600 mg/kg. In the rat study, although increases in serum total protein, albumin and calcium, as well as increased liver and kidney weights, were observed at 400 and/or 1600 mg/kg, no obvious morphological changes were seen. The hemolytic anemia and an increased Heinz body formation were not observed in rats, indicating a species difference. On the basis of these results, the non-toxic dose of ecabapide was considered to be 50 mg/kg in dogs and 100 mg/kg in rats.
Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
T
T
Jindo
Y
Y
Genda
K
K
Kakihata
H
H
Ohno
Y
Y
Akiyama
D000284:Administration, Oral; D000743:Anemia, Hemolytic / Q000139:chemically induced; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000633:toxicity*; D001549:Benzamides / Q000008:administration & dosage / Q000633:toxicity*; D001798:Blood Proteins / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004920:Erythropoiesis / Q000187:drug effects; D005260:Female; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D051381:Rats; D017207:Rats, Sprague-Dawley; D012472:Salivation / Q000187:drug effects; D013154:Spleen / Q000187:drug effects; D013997:Time Factors; D014839:Vomiting / Q000139:chemically induced
D000897:Anti-Ulcer Agents; D001549:Benzamides; D001798:Blood Proteins; C058308:ecabapide