Conroy C W, Maren T H
Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville 32610, USA.
J Ocul Pharmacol Ther. 1999 Apr;15(2):179-87. doi: 10.1089/jop.1999.15.179.
The accession to cornea, aqueous humor and ultimately ciliary process was studied for a series of 6 sulfonamides which differed in their free acid lipophilicities. The drugs were applied as 5 mM solutions at pH 5 in unionized form or in chiefly ionized form at pH 8.4-9.4. These latter solutions contained 10% unionized drug. At 30 minutes post dose corneal drug levels were 2-3 fold higher for ionized compared to unionized application for a given drug. For ionized application there was a direct correlation between corneal drug accumulation and the lipophilicity of the unionized form of the drug. Cornea and aqueous humor drug levels were nearly equal 30 minutes following unionized application but significantly higher in cornea compared to aqueous humor after ionized application, suggesting drug was being retained in the cornea in ionized form. The efficiency of drug accession to ciliary process from cornea was assessed for the different drugs. The greatest accession to ciliary process from cornea as measured by the ratio of the two drug levels was found to correspond to compounds with free acid CHCl3/buffer partition coefficients approximately equal to unity. These results are discussed in terms of possible pathways of drug diffusion in the eye and the known intraocular pressure effects of topically applied sulfonamides.
研究了一系列6种游离酸亲脂性不同的磺胺类药物对角膜、房水以及最终对睫状体的渗透情况。这些药物以5 mM溶液的形式给药，在pH 5时呈非离子化形式，在pH 8.4 - 9.4时主要呈离子化形式。后一种溶液含有10%的非离子化药物。给药后30分钟，对于给定的药物，离子化给药时角膜药物水平比非离子化给药时高2 - 3倍。对于离子化给药，角膜药物蓄积与药物非离子化形式的亲脂性之间存在直接相关性。非离子化给药后30分钟，角膜和房水药物水平几乎相等，但离子化给药后角膜中的药物水平明显高于房水，这表明药物以离子化形式滞留在角膜中。评估了不同药物从角膜向睫状体渗透的效率。通过两种药物水平的比值衡量，发现从角膜向睫状体的最大渗透对应于游离酸氯仿/缓冲液分配系数约等于1的化合物。根据药物在眼内可能的扩散途径以及局部应用磺胺类药物已知的眼压效应讨论了这些结果。
