GRAYBILL JR, NAJVAR LK, BOCANEGRA R, SCOLPINO A, MANNINO RJ, ZARIF L; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1999 Sep 26-29; 39: 583 (abstract no. 2009).
Univ. TX Health Sci. Ctr., San Antonio, TX
Herein are inital in vivo studies of a novel lipid formulation of amphotericin B - cochleate (AMBc) - named for its unique shape and characterized by excellent stability, and ability to target AMB to fungi. Groups of outbred ICR mice were infected intravenously (IV) with approximately 10[6] CFU/mouse of Candida albicans, a dose that is usually lethal in 2 weeks. Groups of 10 mice were treated from day 1 to day 10 post infection with non drug treated Controls, or empty cochleate vehicle Controls (Ctrl) intraperitoneally (IP), AMBc ranging from 0.01 to 20 mg/kg/day IP, or commercial AMB, Fungizone (Fgz), ranging from 0.01 to 4 mg/kg/day IP. Mice were followed for survival through day 30 post infection. For kidney and spleen burdens, groups of 7 mice were treated daily for 7 days and sacrificed on day 8. In study 1 Ctrl mice survived a mean of 8 days, while mice given Fgz at 4 mg/kg/day or AMBc/1 mg/kg/day survived > 30 days (p0.001, Wilcoxon test of life tables). In study 2 Ctrl mice survived a mean of 11 days. AMBc/ Fgz responses were protective in 25/26 mean days survival at 0.1 mg/ kg/day and >30 days at 0.5 mg/kg/day. In a tissue burden study, 3 drugs were compared at 0.1, 1 (Fgz, AMBc and AmBisome) and 10 (AMBc and AmBisome) mg/kg/day. In the kidneys, all regimens were effective, but in the spleen, AMBc was more potent than Fgz at 1 mg/kg/day and equivalent to AmBisome at 10 mg/kg/day. In summary, AMBc is highly effective in murine candidiasis, comparing well with both AmBisome and Fgz. AMBc may have significant clinical potential.
Publication Types:
Keywords:
- AmBisome
- Amphotericin B
- Animals
- Candida albicans
- Candidiasis
- Fat Emulsions, Intravenous
- Kidney
- Lipids
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Spleen
- Vehicles
Other ID:
UI: 102246763
From Meeting Abstracts