Prevention of Cephalosporin Nephrotoxicity by Other Cephalosporins and by Penicillins Without Significant Inhibition of Renal Cortical Uptake

Prevention of cephalosporin nephrotoxicity in animal models by probenecid or p-aminohippurate requires treatment regimens that produce sustained inhibition of cortical accumulation of the toxic antibiotic. In contrast, cephaloridine nephrotoxicity in the rabbit can be prevented by a limited single d...

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Bibliographic Details
Published in:The Journal of infectious diseases 1982-02, Vol.145 (2), p.174-180
Main Authors: Tune, Bruce M., Browning, Marc C., Hsu, Chieh-Yin, Fravert, Doris
Format: Article
Language:English
Subjects:
Animals
Antibiotics
Body weight
Cefazolin - toxicity
Cephaloglycin - toxicity
Cephaloridine - toxicity
Cephalosporins
Cephalosporins - antagonists & inhibitors
Cephalosporins - pharmacology
Cephalosporins - toxicity
Dosage
Female animals
Kidney Cortex - drug effects
Kidneys
Necrosis
Neomycin - toxicity
Nephrotoxicity
Penicillin
Penicillin G - analogs & derivatives
Penicillin G - pharmacology
Penicillins - pharmacology
Rabbits
T tests
Therapeutics
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Summary:Prevention of cephalosporin nephrotoxicity in animal models by probenecid or p-aminohippurate requires treatment regimens that produce sustained inhibition of cortical accumulation of the toxic antibiotic. In contrast, cephaloridine nephrotoxicity in the rabbit can be prevented by a limited single dose of cephalothin. In the present report further studies were done in which it was demonstrated that cephaloridine nephrotoxicity can be prevented by doses of other cephalosporins or penicillins that produce little or no reduction of the cortical concentrations of the toxic cephalosporin. More limited studies revealed similar protection by benzylpenicillin against cephaloglycin, also without reduction of cortical concentration. Finally, similar limited-dose administration of penicillin eliminated the additive toxicity of cefazolin and neomycin. This selective protection against the toxic cephalosporins by the less toxic or nontoxic cephalosporins and by the penicillins, without inhibition of overall cortical accumulation of the toxic antibiotic, may provide a subcellular probe for the study of the molecular basis of cephalosporin nephrotoxicity.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/145.2.174