Pathology of the forestomach in rats treated for 1 year with a new histamine H2-receptor antagonist, SK&F 93479 trihydrochloride.
The new long acting histamine H2-receptor antagonist was administered to rats at doses of 1000, 200 and 40 mg/kg body weight. Forestomach lesions of marked focal hyperplasia and hyperkeratosis were observed at a 48% incidence after 1 year daily gavage dosing with 1000 mg/kg. Lesions of this type were not seen in mid- and low-dose groups. The basal epithelium was convoluted and showed frequent mitotic figures. Two cases (4%) showed hyperplastic epithelium penetrating the muscularis mucosae. Recovery high-dose animals left untreated for a further 20-22 weeks were examined by endoscopy and necropsy and showed the hyperplasia and associated hyperkeratosis to be reversible. As penetration of the muscularis mucosae was only present in two cases at 1 year, the reversibility of this stage could not be assessed and the significance of the lesion will be determined by the results of a 2 year carcinogenicity study.
D000818:Animals; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005260:Female; D006635:Histamine H2 Antagonists / Q000633:toxicity*; D006965:Hyperplasia; D008297:Male; D011744:Pyrimidinones / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors
D006635:Histamine H2 Antagonists; D011744:Pyrimidinones; C033275:SK&F 93479