Abstract
The nephrotoxicity of cefoxitin was studied in a rat model of impaired renal function. Two levels of renal impairment were produced: "moderate," with blood urea concentrations of 100 to 150 mg/100 ml (16.7 to 25.1 mmol/liter) and glomerular filtration rates 25 to 35% of normal, and "severe," with blood urea concentrations greater than 150 mg/100 ml (greater than 25.1 mmol/liter) and glomerular filtration rates 10 to 20% of normal. Sham-operated animals were used as controls. Three dose schedules of cefoxitin were administered to these controls--500, 1,000, and 2,500 mg/kg per day administered as a divided dose for 5 days. Doses given to the moderately and severely uremic animals were adjusted so that serum levels of cefoxitin were similar to those attained in the sham-operated control animals. Concentrations of urea and creatinine in blood, glomerular filtration rates, and the urinary concentrating capacities of the experimental animals were monitored before and after cefoxitin treatment. There was no evidence of nephrotoxicity in even the most challenging experiment, in which blood serum levels of cefoxitin reached 2,000 microgram/ml in animals, with 15% renal function. These findings support available clinical data, suggesting that cefoxitin can be administered safely to patients with compromised renal function.
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Selected References
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- Bell S. M., Wood R. An antibiotic assay method. J Med Lab Technol. 1968 Jan;25(1):27–32. [PubMed] [Google Scholar]
- Dodds M. G., Foord R. D. Enhancement by potent diuretics of renal tubular necrosis induced by cephaloridine. Br J Pharmacol. 1970 Oct;40(2):227–236. doi: 10.1111/j.1476-5381.1970.tb09916.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lawson D. H., Macadam R. F., Singh M. H., Gavras H., Hartz S., Turnbull D., Linton A. L. Effect of furosemide on antibiotic-induced renal damage in rats. J Infect Dis. 1972 Dec;126(6):593–600. doi: 10.1093/infdis/126.6.593. [DOI] [PubMed] [Google Scholar]
- Layzell D., Miller T. Determination of glomerular filtration rate in the rat using 51Cr-EDTA and a single blood sample. Invest Urol. 1975 Nov;13(3):200–204. [PubMed] [Google Scholar]
- Luft F. C., Patel V., Yum M. N., Kleit S. A. Nephrotoxicity of cephalosporin-gentamicin combinations in rats. Antimicrob Agents Chemother. 1976 May;9(5):831–839. doi: 10.1128/aac.9.5.831. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ormrod D., Miller T. Experimental uremia. Description of a model producing varying degrees of stable uremia. Nephron. 1980;26(5):249–254. doi: 10.1159/000181994. [DOI] [PubMed] [Google Scholar]
- Trollfors B., Norrby R., Kristianson K. Effects on renal function of treatment with cefoxitin sodium alone or in combination with furosemide. J Antimicrob Chemother. 1978 Jul;4(B):85–89. doi: 10.1093/jac/4.suppl_b.85. [DOI] [PubMed] [Google Scholar]