title: Ocular absorption of topically applied FK506 from liposomal and oil formulations in the rabbit eye.
abstract: OBJECTIVE
  To investigate the use of topically applied FK506, a new immunosuppressive compound, systemic and ocular absorption was determined in serum and various ocular tissues.
  
  
  METHODS
  Two drops of 20 microliters FK506 were applied using oil dissolved (OD-FK506) or liposome-bound (LIP-FK506) drug. FK506 concentrations were measured at intervals of 30, 60, and 120 minutes by immunoassay.
  
  
  RESULTS
  After application of OD-FK506, the highest concentrations of FK506 were found in the cornea and the conjunctiva (200-1200 ng/g) with substantial drug also present in anterior and posterior sclera. Relatively low concentrations were measured in the aqueous and vitreous humors (0.2-1.0 ng/g) of these animals. Using the same treatment regimen, LIP-FK506 was effective in delivering significantly higher drug concentrations (P < 0.05) to all ocular tissues and particularly aqueous humor (5-28 ng/g) and vitreous humor (12-22 ng/g) at all time points. During the observation period drug concentrations produced by LIP-FK506 remained well above the therapeutic range. FK506 levels were not detectable in serum (< 0.2 ng/ml) with either drug formulation.
  
  
  CONCLUSIONS
  These findings indicate that liposomes may be a promising formulation for topical use of FK506 in ocular immune-mediated diseases.
authors.affiliation: Jules Stein Eye Institute, UCLA School of Medicine.
authors.forename: U
authors.initials: U
authors.lastname: Pleyer
authors.forename: S
authors.initials: S
authors.lastname: Lutz
authors.forename: W J
authors.initials: WJ
authors.lastname: Jusko
authors.forename: K D
authors.initials: KD
authors.lastname: Nguyen
authors.forename: M
authors.initials: M
authors.lastname: Narawane
authors.forename: D
authors.initials: D
authors.lastname: Rückert
authors.forename: B J
authors.initials: BJ
authors.lastname: Mondino
authors.forename: V H
authors.initials: VH
authors.lastname: Lee
authors.forename: K
authors.initials: K
authors.lastname: Nguyen
mesh_terms: D000042:Absorption; D000287:Administration, Topical; D000818:Animals; D004337:Drug Carriers; D005123:Eye / Q000378:metabolism*; D005260:Female; D005614:Freeze Fracturing; D007118:Immunoassay; D008081:Liposomes; D011817:Rabbits; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D016559:Tacrolimus