Heat-treated Fungizone retains amphotericin B antifungal activity without renal toxicity in rats infected with Aspergillus fumigatus.
OBJECTIVE
The purpose of this study was to assess the antifungal activity and renal and hepatic toxicity of amphotericin B (AmpB) following administration of Fungizone (FZ) and a heat-treated form of FZ (HFZ) to rats infected with Aspergillus fumigatus.


METHODS
Infected rats were administered FZ and HFZ at a dosing regimen of 1 mg/kg i.v. once daily for 4 consecutive days. Following administration the number of colony forming units (CFUs) of Aspergillus fumigatus in different organs and serum creatinine concentrations were determined.


RESULTS
FZ and HFZ had similar overall effectiveness in decreasing the total number of Aspergillus fumigatus CFUs found in all organs analyzed compared to controls. Except for the serum creatinine concentrations reported in the nontreated infected control rats, none of the treatment groups tested displayed a greater than 50% increase in serum creatinine.


CONCLUSIONS
Taken together, these findings suggest that HFZ at 1 mg/kg once daily x 4 days appears to be as effective as FZ as an antifungal agent without renal toxicity.
Sivak
Olena
O
Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
Bartlett
Karen
K
Wasan
Kishor M
KM
D000666:Amphotericin B / Q000737:chemistry* / Q000627:therapeutic use* / Q000633:toxicity; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry* / Q000627:therapeutic use* / Q000633:toxicity; D001228:Aspergillosis / Q000188:drug therapy*; D001232:Aspergillus fumigatus / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D006358:Hot Temperature; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000935:Antifungal Agents; D000666:Amphotericin B