[Effect of cefodizime sodium on the kidney function in male rabbits--single and 7-day repeated intravenous...

Renal effects of cefodizime sodium (THR-221) administered by the intravenous route singly and for 7 consecutive days to male rabbits, were compared with those of cefazolin sodium (CEZ) and cephalothin sodium (CET). Four animals were used in each group including control groups. In the single-dose study, THR-221 (600 and 1800 mg/kg) and CET (1800 mg/kg) caused no nephrotoxic effects. In the CEZ groups (600 and 1800 mg/kg), findings indicative of the decreased renal function were obtained: serum urea nitrogen and creatinine levels increased over the control values, and phenolsulfonphthalein (PSP) retention test showed a delay in PSP excretion from the blood. In addition, the white surface of the kidney was macroscopically observed, and microscopic examination revealed renal proximal tubular changes such as necrosis, hyaline cast and calcification, suggesting renal disorders. The repeated-dose study also showed similar results to those described above. Administration of THR-221 (200 and 600 mg/kg/day) and CET (600 mg/kg/day) caused no effects on the kidney. In the CEZ groups (200 and 600 mg/kg/day), serum chemical and PSP test results suggested the decreased renal function, and macroscopic and microscopic findings included organic changes in the kidney. These results suggest that under the conditions tested THR-221 dose not elicit signs of nephrotoxicity in contrast to CEZ, and behaves almost equally to CET.