title: Tropically stable novel oral lipid formulation of amphotericin B (iCo-010): biodistribution and toxicity in a mouse model.
abstract: BACKGROUND
  The purpose of this study was to evaluate the biodistribution and toxicity of amphotericin B (AmB) following multiple oral administrations of a novel tropically stable lipid-based formulation (iCo-010).
  
  
  METHODS
  BALB/c mice were allocated into six groups: oral iCo-010 twice daily for 5 days in the dose of 20, 10, 5 and 2.5 mg/kg; vehicle control; and intravenous boluses of Fungizone 2 mg/kg once daily for 5 days. The animals were sacrificed 12 h following the last administration and blood and tissues were collected.
  
  
  RESULTS
  The plasma concentrations of AmB were similar to previously reported after administration of iCo-009. Somewhat lower concentrations of AmB were detected in reticulo-endothelial system in the case of iCo-010 when compared with iCo-009. The concentration in kidney was higher with iCo-010 than with iCo-009. The creatinine levels in all oral treatment groups were in a normal range as in the case of iCo-009. Administration of Fungizone resulted in elevated plasma creatinine levels. Histopathology analysis detected no GI, liver or kidney toxicity following multiple dose oral administration of iCo-010. Fungizone treatment induced necrotic changes in hepatic and kidney tissues.
  
  
  CONCLUSIONS
  Given the tropical stability of iCo-010, near identical activity against visceral leishmaniasis and significant concentrations in target organs this formulation has a potential to become a treatment of choice in tropical developing countries.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC, Canada V6T 1Z3.
authors.forename: Olena
authors.initials: O
authors.lastname: Sivak
authors.forename: Pavel
authors.initials: P
authors.lastname: Gershkovich
authors.forename: Molly
authors.initials: M
authors.lastname: Lin
authors.forename: Ellen K
authors.initials: EK
authors.lastname: Wasan
authors.forename: Jinying
authors.initials: J
authors.lastname: Zhao
authors.forename: David
authors.initials: D
authors.lastname: Owen
authors.forename: John G
authors.initials: JG
authors.lastname: Clement
authors.forename: Kishor M
authors.initials: KM
authors.lastname: Wasan
mesh_terms: D000284:Administration, Oral; D000666:Amphotericin B / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D002626:Chemistry, Pharmaceutical; D003404:Creatinine / Q000097:blood; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D005260:Female; D007668:Kidney / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D014329:Tropical Climate
chemical_list: D000981:Antiprotozoal Agents; D000666:Amphotericin B; D003404:Creatinine