title: Study of the toxicity of a new lipid complex formulation of amphotericin B.
abstract: OBJECTIVE
  The aim of this study was to evaluate the toxicity of a new lipid complex formulation of amphotericin B (LC-AmB) produced by a simple process.
  
  
  METHODS
  Toxicity was evaluated after daily administration for 21 consecutive days in female CD1 mice. Doses of LC-AmB up to 20 mg/kg were used, and compared with Fungizone at 0.5 mg/kg and Abelcet at 10 mg/kg. Acute toxicity after a single bolus injection was also determined, as well as the haemolytic activity and toxicity to mouse macrophages in vitro.
  
  
  RESULTS
  LC-AmB reduced both the haemolytic activity of amphotericin B and its toxicity towards mouse peritoneal macrophages. Its acute toxicity (LD50 > 200 mg/kg in CD1 mice) was similar to that in the literature for the least toxic lipid formulations of amphotericin B. The relative liver weight increased slightly in mice treated daily with a dose of 20 mg/kg LC-AmB, as did the kidney weight in this group and the group treated with Fungizone. There was also a dose-dependent decrease in the haematocrit with all formulations. All treatments caused significant increases in transaminase levels. Total hepatic CYP 450 was slightly but not significantly increased in the groups treated with 20 mg/kg LC-AmB, Abelcet and Fungizone. However, expression of some isoforms of CYP 450 was reduced, the most marked being the hepatic CYP 3A1 after treatment with 20 mg/kg LC-AmB, Abelcet and Fungizone. The effects on hepatic function are probably related to accumulation in organs rich in phagocytic cells.
  
  
  CONCLUSIONS
  LC-AmB did not induce any new toxicity compared with Abelcet and Fungizone.
authors.affiliation: Laboratoire de Physico-chimie, Pharmacotechnie, Biopharmacie, UMR CNRS 8612, France.
authors.forename: M
authors.initials: M
authors.lastname: Larabi
authors.forename: N
authors.initials: N
authors.lastname: Pages
authors.forename: F
authors.initials: F
authors.lastname: Pons
authors.forename: M
authors.initials: M
authors.lastname: Appel
authors.forename: A
authors.initials: A
authors.lastname: Gulik
authors.forename: J
authors.initials: J
authors.lastname: Schlatter
authors.forename: S
authors.initials: S
authors.lastname: Bouvet
authors.forename: G
authors.initials: G
authors.lastname: Barratt
mesh_terms: D000666:Amphotericin B / Q000633:toxicity*; D000818:Animals; D000935:Antifungal Agents / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010713:Phosphatidylcholines / Q000633:toxicity*; D010715:Phosphatidylglycerols / Q000633:toxicity*; D018675:Toxicity Tests
chemical_list: D000935:Antifungal Agents; D004338:Drug Combinations; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C068538:liposomal amphotericin B; D000666:Amphotericin B; D003577:Cytochrome P-450 Enzyme System