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An Evaluation of the Safety of Ranitidine During Seven Years Daily Oral Administration to Beagle Dogs

Division of Pathology and Toxicology, Glaxo Group Research Limited, Ware, Hertfordshire, SG12 0DJ, UK

S.A.M. Selway

Division of Pathology and Toxicology, Glaxo Group Research Limited, Ware, Hertfordshire, SG12 0DJ, UK

D. Poynter

Division of Pathology and Toxicology, Glaxo Group Research Limited, Ware, Hertfordshire, SG12 0DJ, UK

1 Ranitidine hydrochloride was administered orally to Beagles at doses equivalent to 50 mg once daily, or 5 mg twice daily, of ranitidine base/kg for more than 7 years.

2 Apart from looseness of faeces, seen mainly after doses of 50 mg/kg and only rarely after the first year of such treatment, there were no adverse clinical effects. There were no deaths related to treatment.

3 Periodic gastroscopy revealed nothing abnormal.

4 Peak plasma levels of ranitidine occurred within 2 h of dosing; levels were proportional to the doses administered.

5 There were no major differences in fasting plasma gastrin levels between treated and untreated dogs; the expected increase occurred in response to the provision of food and, predictably, this was greater following a dose of ranitidine.

6 A normal histamine-induced gastric secretory response was demonstrated.

7 Necropsy revealed no lesions of toxicological significance. Macroscopically the stomachs appeared normal but microscopic examination showed some gastritis in both treated and control dogs. No changes in enterochromaffin-like (ECL) cells were detected. Electron microscopy showed unimpaired secretory activity of parietal cells.

8 Thus, after more than 7 years administration to beagle dogs of doses in excess of the normal daily therapeutic dose, the stomachs showed no changes attributable to treatment and their secretory capacity was unimpaired.

Human & Experimental Toxicology, Vol. 8, No. 1, 23-32 (1989)
DOI: 10.1177/096032718900800105


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