The use of commercially available lipid emulsions for the preparation of amphotericin B-lipid admixtures.
The use of Intralipid as a dilution medium for Fungizone, previously proposed by several groups to reduce the toxicity of amphotericin B, is limited by the instability of amphotericin B-lipid admixtures. We have shown that Fungizone-lipid admixtures with three different lipid emulsions can be stabilized by vigorous agitation. Unlike in preparations made by gentle shaking, in stable emulsions made by agitation for 18 h, most of the amphotericin B remains associated with the lipid phase for at least 1 month at 4 degrees C. The MICs of all the admixtures against various Candida spp. were similar to that of Fungizone and did not change following storage for at least 2 weeks at 4 degrees C. Furthermore, the toxicity of the admixtures, as evaluated by their haemolytic activity and amphotericin B-induced K+-leakage from human red blood cells, was much lower than that of Fungizone. Hence, amphotericin B-containing lipid emulsions made by extended agitation may be advantageous in clinical practice as they are efficient, stable, non-toxic and can be easily produced at low cost from commercially available ingredients approved for clinical use.
Shadkhan
Y
Y
Department of Physiology, Rabin Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
Segal
E
E
Bor
A
A
Gov
Y
Y
Rubin
M
M
Lichtenberg
D
D
D000666:Amphotericin B / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D000935:Antifungal Agents / Q000008:administration & dosage*; D004655:Emulsions; D006801:Humans; D008055:Lipids / Q000008:administration & dosage; D008826:Microbial Sensitivity Tests
D000935:Antifungal Agents; D004655:Emulsions; D008055:Lipids; D000666:Amphotericin B