[26-week intravenous toxicity test of cefpiramide in cynomolgus monkeys]

A chronic toxicity of cefpiramide (CPM) was studied in Cynomolgus monkeys. Groups of 4 males and 4 females were given daily doses of 100, 300 mg/kg or 600 mg/kg by intravenous administration for 26 weeks. Another group of 4 males and 4 females was given physiological saline and served as the control. In CPM groups, diarrhea or soft feces was observed after the commencement of administration at every doses. The frequency of these signs decreased as the study progressed and animals at lower doses returned to normal earlier. There were no treatment-related changes in body weights, fecal occult blood and electrocardiograms. A female in the 600 mg/kg group died after 13 weeks of treatment. The cause of death was assumed to be an acute myocardial necrosis resulting from thromboarteritis. It was not considered to be treatment-related. Ophthalmological examination revealed no abnormalities attributable to the treatment. Erythrocyte counts, hemoglobin and hematocrit values decreased in 3 animals receiving 600 mg/kg of the drug. The changes, however, were transient at least in 2 of these animals. There were no effects on plasma biochemical and urinalysis parameters. Small yellow spotes were noted in the renal cortex of 2 monkeys in the 600 mg/kg group at necropsy. Liver and kidneys were slightly heavier in animals receiving 600 mg/kg. Histopathological examinations revealed focal nonsuppurative interstitial nephritis in 1 animal given 300 mg/kg and 5 animals given 600 mg/kg. No treatment-related changes were observed in other organs and tissues. From these results, the maximum non-effective dose level of CPM was considered to be 100 mg/kg.