title: Pharmacokinetics, tissue distribution and immunomodulatory effect of intralipid formulation of nystatin in mice.
abstract: OBJECTIVE
  We developed a novel lipid formulation of nystatin suitable for parenteral administration, nystatin-intralipid (NYT-IL), with antifungal activity and reduced toxicity in mice. We investigated the pharmacokinetics, tissue distribution and immunomodulatory effect of NYT-IL in mice.
  
  
  METHODS
  Nystatin levels in serum and organs were determined using HPLC after NYT-IL or nystatin administration in mice. The levels of the pro-inflammatory cytokines tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) and the anti-inflammatory cytokine interleukin 10 (IL-10) produced by splenocytes from mice injected with NYT-IL or nystatin were evaluated by an ELISA assay.
  
  
  RESULTS
  Injection of NYT-IL resulted in similar levels and similar kinetics of nystatin in serum, higher concentrations in the liver and lower concentrations in the kidneys, in comparison with nystatin injection. Injection of mice with NYT-IL yielded higher levels of IL-10 than that of nystatin, whereas the levels of TNF-α and IFN-γ induced by NYT-IL were lower than those elicited by nystatin.
  
  
  CONCLUSIONS
  Since polyene treatment is associated with nephrotoxicity, lower levels of nystatin in the kidneys following NYT-IL injection suggest the possibility of reduced toxicity. As the acute infusion-related adverse effects associated with polyene treatment are considered to be induced by pro-inflammatory cytokines, a higher level of anti-inflammatory and lower levels of pro-inflammatory cytokines elicited by NYT-IL administration suggest the possibility of amelioration of such effects. In summary, the altered pharmacokinetics, tissue distribution and immune response due to the use of this intralipid formulation of nystatin merit further research towards the development of a therapeutic agent against invasive mycoses.
authors.affiliation: Department of Clinical Microbiology and Immunology, Sackler School of Medicine,  Tel-Aviv University, Tel-Aviv,  Israel.
authors.forename: Rita
authors.initials: R
authors.lastname: Semis
authors.forename: Shai Shmuel
authors.initials: SS
authors.lastname: Nili
authors.forename: Ariel
authors.initials: A
authors.lastname: Munitz
authors.forename: Zeev
authors.initials: Z
authors.lastname: Zaslavsky
authors.forename: Itzhack
authors.initials: I
authors.lastname: Polacheck
authors.forename: Esther
authors.initials: E
authors.lastname: Segal
mesh_terms: D000825:Animal Structures / Q000737:chemistry; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D016207:Cytokines / Q000378:metabolism; D004655:Emulsions / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008813:Mice, Inbred ICR; D009761:Nystatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D010743:Phospholipids / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D044967:Serum / Q000737:chemistry; D013024:Soybean Oil / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D013154:Spleen / Q000276:immunology; D014018:Tissue Distribution
chemical_list: D000935:Antifungal Agents; D016207:Cytokines; D004655:Emulsions; D007155:Immunologic Factors; D010743:Phospholipids; C545823:soybean oil, phospholipid emulsion; D009761:Nystatin; D013024:Soybean Oil