Ocular absorption of topically applied FK506 from liposomal and oil formulations in the rabbit eye.
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.
Pleyer
U
U
Jules Stein Eye Institute, UCLA School of Medicine.
Lutz
S
S
Jusko
W J
WJ
Nguyen
K D
KD
Narawane
M
M
Rückert
D
D
Mondino
B J
BJ
Lee
V H
VH
Nguyen
K
K
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
D004337:Drug Carriers; D008081:Liposomes; D016559:Tacrolimus