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[Nephrotoxicity of cefpirome sulfate in rabbits--single and multiple intravenous administration]
T Deki1, A Matsuoka, K Marutani
1Research and Development Division, Chugai Pharmaceutical Co., Ltd., Nagano, Japan.
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.
Insights
Cefpirome sulfate (CPR) exhibits dose-dependent nephrotoxicity in rabbits, comparable to cefazolin sodium (CEZ) but less than cefaloridine (CER). Higher doses of CPR caused kidney damage, particularly in single administrations.
Area of Science:
- Pharmacology
- Nephrology
- Toxicology
Background:
- Antibiotic-induced nephrotoxicity is a significant clinical concern.
- Cefpirome sulfate (CPR) is a cephalosporin antibiotic requiring safety evaluation.
- Comparative nephrotoxicity studies are crucial for drug development.
Purpose of the Study:
- To evaluate the nephrotoxic potential of cefpirome sulfate (CPR) in comparison to cefazolin sodium (CEZ) and cefaloridine (CER).
- To determine dose-dependent nephrotoxicity of CPR through single and multiple intravenous administrations in rabbits.
Main Methods:
- Single and repeated intravenous administrations of CPR, CEZ, and CER to male Japanese white rabbits.
- Monitoring of clinical signs, urinalysis (proteinuria, glucosuria), serum biochemistry (urea nitrogen, creatinine, uric acid), and renal phenolsulfonphthalein (PSP) excretion.
- Histopathological examination of kidney tissues for tubular damage, necrosis, and calcification.
Main Results:
- Single administration: CPR and CEZ showed nephrotoxicity at ≥500 mg/kg, with findings including renal function impairment and proximal tubular damage.
- Repeated administration: CPR and CEZ at ≤100 mg/kg showed no nephrotoxicity; higher doses (≥200 mg/kg CPR, ≥200 mg/kg CEZ) induced similar renal biochemical and histopathological changes.
- CPR demonstrated less nephrotoxicity than CER and comparable toxicity to CEZ, with variations between single and multiple dose studies.
Conclusions:
- Cefpirome sulfate exhibits dose-dependent nephrotoxicity in rabbits.
- CPR's nephrotoxic potential is comparable to CEZ but lower than CER.
- The study provides valuable data for assessing the renal safety profile of CPR in clinical settings.