Toxicity of the novel anti-peptic ulcer agent catena-(S)-[mu-[Na- (3-aminopropionyl)histidinato(2-)-N1,N2,Q:N tau]-zinc in male cynomolgus monkeys.
A preliminary dose-range finding study and a 13-week toxicity study were performed in male cynomolgus monkeys with catena-(S)-[mu-[N a-(3-aminopropionyl) histidinato (2-)-N1,N2,O:N tau]-zinc] (Z-103, CAS 107667-60-7), a novel anti-peptic ulcer agent, as part of a safety evaluation program. In the preliminary ascending dose study emesis was observed in animals treated at 625 mg/kg and transient reductions in food intake with associated body weight loss in a male treated at 625 or 312.5 mg/kg. Plasma zinc levels were also increased in all animals treated at 625 or 312.5 mg/kg. As a result dosages of 0, 20, 63 and 200 mg/kg/day were selected for the 13-week toxicity study. In this study, treatment-related changes were confined to the 200 mg/kg/day dosage and consisted of emesis, piloerection and transient body weight loss in one animal, increased plasma zinc concentrations, and zinc and copper deposition in the liver and kidneys without any associated morphological change. The no observed effect level was estimated to be 63 mg/kg/day in this study.
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Huntingdon Research Centre Ltd, Cambridgeshire, England.
Deoraj
P
P
Gopinath
C
C
Crook
D
D
Matsuda
K
K
D000818:Animals; D000897:Anti-Ulcer Agents / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002336:Carnosine / Q000031:analogs & derivatives*; D003300:Copper / Q000378:metabolism; D004151:Dipeptides / Q000633:toxicity*; D004435:Eating / Q000187:drug effects; D004562:Electrocardiography / Q000187:drug effects; D005128:Eye Diseases / Q000139:chemically induced / Q000473:pathology; D005260:Female; D007501:Iron / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D009942:Organometallic Compounds / Q000633:toxicity*; D010863:Piloerection / Q000187:drug effects; D014839:Vomiting / Q000139:chemically induced; D015032:Zinc / Q000378:metabolism; D017967:Zinc Compounds
D000897:Anti-Ulcer Agents; D004151:Dipeptides; D009942:Organometallic Compounds; D017967:Zinc Compounds; C061957:polaprezinc; D003300:Copper; D002336:Carnosine; D007501:Iron; D015032:Zinc