Grass G M, Wood R W, Robinson J R
Invest Ophthalmol Vis Sci. 1985 Jan;26(1):110-3.
Corneal penetration studies have been conducted in unanesthetized albino rabbits using various organic compounds representing both polar and nonpolar species. In the presence of calcium chelating agents, polar compounds generally demonstrate an increase in corneal penetration. Evidence that this corneal effect is reversible is presented. Concomitant with an increase in both corneal and aqueous humor drug levels was a decrease in drug concentration in both iris and conjunctival tissues tentatively attributed to chelation effects on vascular permeability of these tissues. EDTA, a known calcium chelator, was shown to penetrate the cornea, conjunctiva, and iris/ciliary body from a topically applied dose. The implications of this observation pertain to both toxicity effects, when EDTA is incorporated into ocular drug products for stability purposes, and novel strategems for improving ocular bioavailability of topically applied drugs.
已使用代表极性和非极性物种的各种有机化合物，在未麻醉的白化兔身上进行了角膜渗透研究。在存在钙螯合剂的情况下，极性化合物通常表现出角膜渗透性增加。文中给出了这种角膜效应是可逆的证据。随着角膜和房水中药物水平的增加，虹膜和结膜组织中的药物浓度降低，这初步归因于螯合剂对这些组织血管通透性的影响。已知的钙螯合剂乙二胺四乙酸（EDTA）经局部给药后可穿透角膜、结膜和虹膜/睫状体。这一观察结果的意义既涉及将EDTA用于眼部药物产品以提高稳定性时的毒性影响，也涉及提高局部应用药物眼部生物利用度的新策略。
