[6-week intravenous toxicity test of cefpiramide in rhesus monkeys]

A subchronic toxicity of cefpiramide (CPM) was studied in rhesus monkeys. The drug was administered intravenously to 4 groups of 2 males and 2 females each at a daily dose of 0, 100, 300 mg/kg and 1,000 mg/kg, respectively, for 6 weeks. Vomiting and diarrhea were observed at every dose of CPM, more frequently at the beginning of the treatment period. In addition, salivation was observed at 300 mg/kg or more and a transient subdued mood and inappetence at 1,000 mg/kg. A slight decrease of body weight was noted in a female given 1,000 mg/kg. There were no treatment-related changes in fecal occult blood test and electrocardiograms. Ophthalmological examinations showed no abnormalities being attributable to the treatment. A transient or slight anemia was observed in 2 monkeys receiving 1,000 mg/kg. Examination of bone marrow revealed no abnormalities. There were no effects on plasma biochemical parameters. In urinalysis, a female in the 1,000 mg/kg group showed a glycosuria. Kidneys of 3 animals given 1,000 mg/kg were pale at necropsy. Liver and kidneys were heavier in some animals at 300 mg/kg or more and at 1,000 mg/kg, respectively. Histological examination revealed a multifocal degeneration and regeneration of the proximal renal tubular epithelium in all animals receiving 1,000 mg/kg. No treatment-related changes were encountered in other organs and tissues. From these results, the maximum non-effective dose level of CPM was considered to be 300 mg/kg.