Thirteen-week repeated oral dose toxicity study of ecabapide, a gastroprokinetic drug, in dogs and rats.

Abstract

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.

• Authors: T Jindo, Y Genda, K Kakihata, H Ohno, Y Akiyama
• Journal: The Journal of toxicological sciences (J Toxicol Sci) Vol. 23 Suppl 3 Pg. 561-74 (Jul 1998) ISSN: 0388-1350 [Print] Japan
• PMID: 9760413 (Publication Type: Journal Article)

Chemical References

• Anti-Ulcer Agents
• Benzamides
• Blood Proteins
• ecabapide

Topics

• Administration, Oral
• Anemia, Hemolytic (chemically induced)
• Animals
• Anti-Ulcer Agents (administration & dosage, toxicity)
• Benzamides (administration & dosage, toxicity)
• Blood Proteins (metabolism)
• Body Weight (drug effects)
• Dogs
• Dose-Response Relationship, Drug
• Erythropoiesis (drug effects)
• Female
• Kidney (drug effects)
• Liver (drug effects)
• Male
• No-Observed-Adverse-Effect Level
• Rats
• Rats, Sprague-Dawley
• Salivation (drug effects)
• Spleen (drug effects)
• Time Factors
• Vomiting (chemically induced)