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  • Title: Safety evaluation of cimetidine: 54 month interim report on long-term study in dogs.
    Author: Crean GP, Leslie GB, Walker TF, Whitehead SM, Roe FJ.
    Journal: J Appl Toxicol; 1981 Jun; 1(3):159-64. PubMed ID: 7185881.
    Abstract:
    Cimetidine [N"-cyano-N-methyl-N'-2[(5-methylimidazol-4-yl)methylthio]ethyl guanidine] was administered orally to eight male and four female beagle dogs at a dose level of 144 mg per kg bodyweight per day. Four males and two females received placebo tablets. Dosing began in March 1976. During the first 26 months of dosing the animals became obese--the control animals more so than the cimetidine-treated. Since month 27 feeding time was restricted and there has been an overall weight loss. Some control animals are still obese. One control male and one dosed female have been killed because they developed convulsions. No treatment-related effects on haematology, clinical biochemistry, urinalysis, electrocardiography or clinical condition have been seen. Three out of the five surviving control animals but none of the 11 surviving cimetidine-dosed animals have developed cataracts. Biopsies of gastric mucosa taken during endoscopy in months 41, 47 and 53 have shown no changes attributable to cimetidine treatment.
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