Saperconazole therapy of murine disseminated candidiasis: efficacy and interactions with amphotericin B.
The efficacy of a new triazole antifungal agent, saperconazole, in a murine model of disseminated candidiasis was studied. Mice were intravenously infected with Candida albicans blastoconidia and treated for 14 days with oral saperconazole, intraperitoneal amphotericin B, or a combination of these. Amphotericin B alone was the most efficacious in prolonging survival and in decreasing renal colony counts, usually with complete sterilization of the kidneys by the end of the treatment course. Saperconazole improved survival rates and effected a decrease in renal colony counts, but kidneys were not microbiologically sterilized. Combination therapy with saperconazole and amphotericin B did not result in a decrease in the efficacy of amphotericin B by either end point (survival or renal colony counts). High-pressure liquid chromatographic analysis of saperconazole concentrations in serum indicated low levels of absorption of the drug. We conclude that saperconazole is effective in the treatment of murine invasive candidiasis and that the theoretical concern about adverse interactions between the two drugs does not apply to the dosages studied in these experiments.
Sugar
A M
AM
Evans Memorial Department of Clinical Research, Boston University Medical Center Hospital, Massachusetts.
Salibian
M
M
Goldani
L Z
LZ
D000042:Absorption; D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D001393:Azoles / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D002177:Candidiasis / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004347:Drug Interactions; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D007668:Kidney / Q000382:microbiology; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR
D001393:Azoles; D000666:Amphotericin B; C060571:saperconazole