Pleyer U, Lutz S, Jusko W J, Nguyen K D, Narawane M, Rückert D, Mondino B J, Lee V H, Nguyen K
Jules Stein Eye Institute, UCLA School of Medicine.
Invest Ophthalmol Vis Sci. 1993 Aug;34(9):2737-42.
To investigate the use of topically applied FK506, a new immunosuppressive compound, systemic and ocular absorption was determined in serum and various ocular tissues.
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.
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.
These findings indicate that liposomes may be a promising formulation for topical use of FK506 in ocular immune-mediated diseases.
研究局部应用新型免疫抑制化合物FK506时，其在血清和各种眼组织中的全身及眼部吸收情况。
使用油溶型（OD - FK506）或脂质体结合型（LIP - FK506）药物滴入2滴20微升的FK506。通过免疫测定法在30、60和120分钟的时间间隔测量FK506浓度。
应用OD - FK506后，角膜和结膜中FK506浓度最高（200 - 1200纳克/克），在前、后巩膜中也存在大量药物。这些动物的房水和玻璃体液中测得的浓度相对较低（0.2 - 1.0纳克/克）。采用相同的治疗方案，LIP - FK506在所有时间点均能有效地将显著更高的药物浓度（P < 0.05）输送到所有眼组织，尤其是房水（5 - 28纳克/克）和玻璃体液（12 - 22纳克/克）。在观察期内，LIP - FK506产生的药物浓度始终远高于治疗范围。两种药物制剂在血清中均未检测到FK506水平（< 0.2纳克/毫升）。
这些发现表明脂质体可能是FK506在眼部免疫介导疾病局部应用中的一种有前景的制剂。
