Nephrotoxicity of amphotericin B in rats: effects of the time of administration.

Amphotericin B is a potentially nephrotoxic agent used for the treatment of severe mycoses and numerous fungal infections. Temporal variation in the nephrotoxicity of amphotericin B was studied in rats maintained on a light-dark period of 14 hrs of light and 10 hrs of darkness (light on: 06h00). Subgroups of animals were treated with a single daily i.p. dose of either 5% dextrose or amphotericin B (10 mg/kg/day) given at either 07h00, 13h00, 19h00 or 01h00 for 4 and 10 days. On day 4, no significant difference was observed in any parameter studied. On day 10, the cellular regeneration ([3H]-thymidine incorporation into DNA of renal cortex)(p<0.01), BUN levels (p<0.05), serum creatinine (p<0.05), and accumulation of amphotericin B in the renal cortex (p<0.05) were significantly higher when animals were treated with similar subcellular localization of amphotericin B in the proximal tubular cells of the renal cortex. These results showed a temporal variation in the nephrotoxicity of amphotericin B (peak toxicity occurred at 07h00) which is different from that of other nephrotoxic antibiotics such as aminoglycosides.