NEPHROTOXICITY OF AMPHOTERICIN-B IN RATS - EFFECTS OF THE TIME OF ADMINISTRATION

Amphotericin B is a potentially nephrotoxic agent used for the treatme nt of severe mycoses and numerous fungal infections. Temporal variatio n in the nephrotoxicity of amphotericin B was studied in rats maintain ed on a light-dark period of 14 hrs of light and 10 hrs of darkness (l ight 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) give n 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 da y 10, the cellular regeneration ([H-3]-thymidine incorporation into DN A 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 amph otericin B at 07h00 than at any other time of day. Immunogold labeling showed a similar subcellular localization of amphotericin B in the pr oximal tubular cells of the renal cortex. These results showed a tempo ral variation in the nephrotoxicity of amphotericin B (peak toxicity o ccurred at 07h00) which is different from that of other nephrotoxic an tibiotics such as aminoglycosides.