NEPHROTOXICITY OF CEFCLIDIN IN RATS

Repeated intravenous administration for 7, 14 and 21 days

Abstract

Nephrotoxicity of cefclidin (CFCL) was studied and compared with those of cefazolin (CEZ), cephalothin (CET) and cephaloridine (CER). The rats were treated intravenously with 300 or 1, 000mg/kg of CFCL, 1, 000mg/kg of CEZ and CET, and 500 mg/kg of CER (CER dosage was changed from 750mg/kg to 500mg/kg on day 6 or 7) for 7, 14 and 21 days. There were deaths in only rats given 750mg/kg of CER. In the CFCL treated groups, eosinophilic granules in the proximal tubular epithelia showed a dose-related increase. Slightly vacuolar degeneration of the proximal tubular epithelia were observed in the rats treated with 1, 000 mg/kg. A significantly decreased Na⁺, and increased protein and ketone body in the urine were detected in the rats treated with 1, 000mg/kg for 21 days. In CEZ and CET treated groups, swelling of the proximal tubular epithelia and dilatation of the renal tubules in the cortex were observed in addition to the CFCL induced changes. Urinary Clwas decreased in CEZ treated rats and urinary Na⁺was increased in CET treated rats. In CER treated group, elevation of plasma urea nitrogen, decrease of urinary creatinine and endogeneous creatine clearance, and degeneration or necrosis of the tubular epithelia in the cortex were observed. These results indicated that the order of nephrotoxic potential of the four cephem was CER>CEZ>CET>CFCL.