NEPHROTOXICITY OF CEFODIZIME SODIUM IN RATS : Single and 14-day repeated intravenous administration

Abstract

Nephrotoxicity of cefodizime sodium (THR-221), a new cephem antibiotic, was studied in rats by comparing its toxic effect with those of other cephem antibiotics including cephaloridine (CER), cefazolin (CEZ) and cefmetazol (CMZ). Each drug was administered single and consecutive 14-day dosage with its alone or in combination with either furosemide or gentamicin. The results are summarized as follows : 1. In the single dosage study, the rats treated with THR-221 at dose levels of 1200mg/kg and more showed slight changes in urinary protein and glucose. In rats treated with CER at a dose of 1200mg/kg, creatinine level in plasma and weights of kidneys were increased, and degeneration and/or necrosis of the renal proximal tubular epithelia were observed. Furthermore, by the consecutive dosage of CER at a dose of 1000mg/kg, remarkable renal responses including increase in urinary protein and glucose, and weights of kidneys, were observed. In addition, histopathological examinations showed degeneration and/or regeneration of the renal proximal tubular epithelia. 2. No enhanced effect of nephrotoxicity by combination with furosemide or gentamicin was observed except in case of combination of CER with furosemide. 3. The above results indicate that the nephrotoxic potency among these four antibiotics on the single and consecutive dosage studies is CER>>THR-221≥CEZ ≒CMZ and CER>>THR-221≒CEZ≒CMZ, in the decreasing order.