Experimental studies on the nephrotoxicity of amphotericin B in rats

J Antimicrob Chemother. 1991 Aug;28(2):271-81. doi: 10.1093/jac/28.2.271.

Abstract

The renal effects of amphotericin B alone and in combination with cyclosporin A, tobramycin, fosfomycin, D-glucaro-1,5-lactam and verapamil were studied in rats. The parameters for nephrotoxicity were urinary loss of tubular cells and malate dehydrogenase, as well as creatinine clearance. Repeated intraperitoneal injections of amphotericin B led to an increase of urinary tubular cell elimination and malate-dehydrogenase. After co-administration of amphotericin B and cyclosporin A, the urinary loss of tubular cells increased and creatinine clearance was reduced. A combination of amphotericin B and tobramycin reduced tubular cell elimination but the creatinine clearance improved. When verapamil was combined with amphotericin B, endogenous creatinine clearance increased, though the loss of tubular cells was elevated. Furthermore, fosfomycin reduced the loss of tubular cells and improved renal functional parameters in combination with amphotericin B. In addition, D-glucaro-1,5-lactam was found to reduce the urinary loss of tubular cells induced by amphotericin B.

Publication types

  • Comparative Study

MeSH terms

  • Amphotericin B / toxicity*
  • Animals
  • Creatinine / blood
  • Creatinine / urine
  • Cyclosporine / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Female
  • Kidney Tubules / cytology
  • Kidney Tubules / drug effects*
  • Kidney Tubules / metabolism
  • Rats
  • Rats, Inbred Strains
  • Tobramycin / toxicity
  • Urination / drug effects
  • Verapamil / pharmacology

Substances

  • Amphotericin B
  • Cyclosporine
  • Creatinine
  • Verapamil
  • Tobramycin