Tissue distribution of amphotericin B lipid complex in laboratory animals

J Pharm Pharmacol. 1991 Dec;43(12):831-5. doi: 10.1111/j.2042-7158.1991.tb03189.x.

Abstract

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.

MeSH terms

  • Amphotericin B / administration & dosage
  • Amphotericin B / pharmacokinetics*
  • Animals
  • Chromatography, High Pressure Liquid
  • Female
  • Injections, Intraperitoneal
  • Injections, Intravenous
  • Kidney Function Tests
  • Liposomes
  • Liver Function Tests
  • Mice
  • Particle Size
  • Rats
  • Rats, Inbred Strains
  • Tissue Distribution

Substances

  • Liposomes
  • Amphotericin B