OCULAR ABSORPTION OF TOPICALLY APPLIED FK506 FROM LIPOSOMAL AND OIL FORMULATIONS IN THE RABBIT EYE

Purpose. To investigate the use of topically applied FK506, a new immu nosuppressive compound, systemic and ocular absorption was determined in serum and various ocular tissues. Methods. Two drops of 20 mul FK50 6 were applied using oil dissolved (OD-FK506) or liposome-bound (LIP-F K506) drug. FK506 concentrations were measured at intervals of 30, 60, and 120 minutes by immunoassay. Results. After application of OD-FK50 6, the highest concentrations of FK506 were found in the cornea and th e conjunctiva (200-1200 ng/g) with substantial drug also present in an terior and posterior sclera. Relatively low concentrations were measur ed 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 deliveri ng significantly higher drug concentrations (P < 0.05) to all ocular t issues and particularly aqueous humor (5-28 ng/g) and vitreous humor ( 12-22 ng/g) at all time points. During the observation period drug con centrations produced by LIP-FK506 remained well above the therapeutic range. FK506 levels were not detectable in serum (<0.2 ng/ml) with eit her drug formulation. Conclusion. These findings indicate that liposom es may be a promising formulation for topical use of FK506 in ocular i mmune-mediated diseases.