PURPOSE: 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. CONCLUSION: These findings indicate that liposomes may be a promising formulation for topical use of FK506 in ocular immune-mediated diseases.
PURPOSE: 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. CONCLUSION: These findings indicate that liposomes may be a promising formulation for topical use of FK506 in ocular immune-mediated diseases.