Tissue distribution of amphotericin B lipid complex in laboratory animals.
Amphotericin B lipid complex (ABLC), under development for the treatment of serious fungal disease, is not a true liposome but a complex of amphotericin B, dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol with a particle size range of 1.6-6.0 microns. Tissue distribution of ABLC was determined in mice and rats after i.v. or i.p. administration. ABLC resembles typical liposomal preparations with amphotericin B concentrating in the reticuloendothelial system. After a single i.v. treatment with ABLC, amphotericin B was present in high concentrations in liver, lung and spleen of mice and rats while plasma levels were consistently low. Mouse liver contained 48% of the administered dose 1 h after treatment and always contained the largest amount of amphotericin B after ABLC treatment. In mice treated once daily for 7 consecutive days with 10 mg kg-1 ABLC, liver amphotericin B concentration reached 377 micrograms g-1. Tissue concentrations of amphotericin B were substantially lower when ABLC was given i.p. instead of i.v. with reticuloendothelial tissues containing 2- to 7-fold more after i.v. treatment. Animals treated with 10 mg kg-1 ABLC for 14 consecutive days showed no overt signs of toxicity and had only transient changes in liver and kidney function after treatment.
Department of Microbiology, Bristol-Myers Squibb Company, Princeton, New Jersey 08543-4000.
S J
SJ
Olsen
M R
MR
Swerdel
B
B
Blue
J M
JM
Clark
D P
DP
Bonner
D000666:Amphotericin B / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007677:Kidney Function Tests; D008081:Liposomes; D008111:Liver Function Tests; D051379:Mice; D010316:Particle Size; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D008081:Liposomes; D000666:Amphotericin B