title: Visceral leishmaniasis affects liver and spleen concentrations of amphotericin B following administration to mice.
abstract: OBJECTIVE
  To assess the impact of visceral leishmaniasis (VL) on the concentration of amphotericin B (AmB) recovered in the liver and spleen following either intravenous (AmBisome) or oral (iCo-009) AmB administration to mice.
  
  
  METHODS
  Livers and spleens previously obtained from VL-infected BALB/c mice (following intravenous AmBisome or oral AmB treatments) were analysed for AmB concentrations. Then, non-infected BALB/c mice were divided into three treatment groups: a single dose of intravenous AmBisome (2 mg/kg, n = 5); and oral AmB every 12 h for 5 days (10 mg/kg, n = 6 and 20 mg/kg, n = 6). The animals were sacrificed 7 days after the initiation of the treatment and the livers and spleens were harvested for drug analysis by HPLC.
  
  
  RESULTS
  The single intravenous injection of AmBisome resulted in a 77-fold lower concentration of AmB in infected compared with non-infected liver tissue, while the difference in AmB concentration in the spleen was only 5-fold. The multiple dose oral administration of AmB resulted in a 3-fold lower concentration of AmB in infected compared with non-infected livers for both oral doses, while the differences in AmB concentrations in the spleen were not statistically different for the oral treatment groups.
  
  
  CONCLUSIONS
  VL significantly lowered the concentration of AmB in the liver and the spleen when compared with uninfected animals. This effect seems to correlate with the degree of infection of the tissue. In the case of the intravenous liposomal formulation (AmBisome), the differences between the infected and non-infected tissues are of a higher magnitude than in the case of orally administered AmB (iCo-009).
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC, V6T 1Z3, Canada. pgershko@interchange.ubc.ca
authors.forename: Pavel
authors.initials: P
authors.lastname: Gershkovich
authors.forename: Ellen K
authors.initials: EK
authors.lastname: Wasan
authors.forename: Olena
authors.initials: O
authors.lastname: Sivak
authors.forename: Raymond
authors.initials: R
authors.lastname: Li
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zhu
authors.forename: Karl A
authors.initials: KA
authors.lastname: Werbovetz
authors.forename: Richard R
authors.initials: RR
authors.lastname: Tidwell
authors.forename: John G
authors.initials: JG
authors.lastname: Clement
authors.forename: Sheila J
authors.initials: SJ
authors.lastname: Thornton
authors.forename: Kishor M
authors.initials: KM
authors.lastname: Wasan
mesh_terms: D000284:Administration, Oral; D000666:Amphotericin B / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007275:Injections, Intravenous; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008099:Liver / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000737:chemistry*
chemical_list: D000981:Antiprotozoal Agents; D000666:Amphotericin B