Subchronic and chronic toxicity of the new antibiotic cefpirome in rats

Subchronic and chronic toxicity studies in rats were performed with 3-[(2,3-Cyclopenteno-1-pyridinium)-methyl]- 7-[2-syn-methoximino-2-(2-aminothiazol-4-yl)-acetamido] -ceph-3-em-4- carboxylate (cefpirome, HR 810), a new cephalosporin derivative. In subchronic (14 day) studies cefpirome was intravenously administered in dose levels up to 1500 mg/kg/d with good kidney tolerance. Signs of renal functional impairment were observed (800 and 1500 mg/kg) but histologically no morphological changes could be detected. The chronic intraperitoneal administration (90 day) of cefpirome at dose levels of 400 or 1600 mg/kg/d resulted in some reversible changes in hematology (slight anemia), serum-chemistry parameters (liver), urinalysis (proteinuria), and histopathology (increased numbers and enlargement of lysosomes in proximal tubular epithelia of the kidneys and pigment deposits in follicle epithelia of the thyroids), predominantly in high-dose animals. The "no effect level" is considered to be 100 mg/kg/d in this study.