NEPHROTOXICITY OF CEFPIROME SULFATE IN RABBITS : Single and Multiple Intravenous Administration

Abstract

Nephrotoxic potential of cefpirome sulfate (CPR) was examined by single and multiple intravenous administrations to Japanese white male rabbits. In single administration studies, no nephrotoxic symptoms were observed at the dose level of 320 mg/kg of CPR or less. At the dose level of 500 mg/kg or more, nephrotoxic findings were noted in both CPR and cefazolin sodium(CEZ) groups, such as proteinuria, glucosuria, increase in serum level of urea nitrogen, creatinine and uric acid, and necrosis and calcification in the proximal tubular epithelium of kidney. Renal phenolsulfonphthalein(PSP) excretion was suppressed at the dose level of 500 mg/kg of CPR or more, and 2000 mg/kg of CEZ. In 14 and 21 days repeated administration studies, no nephrotoxic symptoms were observed at the dose level of 100 mg/kg of CPR and CEZ or less. At the dose level of 200 mg/kg of CPR or more, urinary and serum biochemical findings mentioned above were observed, and histopathological changes in the kidney described above were added in 400 mg/kg group. The similar nephrotoxic symptoms including histopathological changes of the kidney were observed in the groups of 100 mg/kg of cefaloridine(CER) and 200 mg/kg of CEZ. In addition, renal PSP excretion was suppressed in the group of 200 mg/kg of CEZ. The results would suggest that CPR is less nephrotoxic than CER and that the nephrotoxic potential of CPR is comparable to CEZ because CPR caused more severe renal failures in single administration study and less severe renal failures in multiple administration study than CEZ.