Subacute intravenous toxicity studies of biapenem in dogs

Abstract

As part of the preclinical safety evaluation of biapenem (BIPM), one month and 3 months intravenous toxicity studies were carried out in dogs. BIPM was administered intravenously with a daily dose of 0, 30, 100 or 300 mg/kg/day for one month in male dogs, and 0, 20, 60 or 200 mg/kg/day for three months in male and female dogs.
1. Drug-related deaths occurred in two of five dogs from the 200 mg/kg/group in the three month toxicity study.
2. There were decreases in body weight in the 100 and 300 mg/kg groups in the one month toxicity study, and in the 60 and 200 mg/kg groups in the three month toxicity study.
3. Abnormal feces such as soft or gelatinous feces were observed in the 100 and 300 mg/kg groups in the one month toxicity study, and in the 60 and 200 mg/kg groups in the three month toxicity study.
4. Decreases in serum total protein and albumin, and increases in triglycerides, phospholipid and total cholesterol were observed in the 300 mg/kg group in the one month toxicity study.
5. Histopathological examination revealed renal tubular hydropic change, mucosal hemorrhage in the large intestine and lymphoid depletion in the thymus and spleen in the 100 and 300 mg/kg groups of the one month toxicity study.
6. In the recovery period of the three month toxicity study, no abnormal findings were found in any examination.
From these results, the non-toxic doses of BIPM in dogs were estimated as 30 mg/kg/day in the one month toxicity study, and 20 mg/kg/day in the three month toxicity study.