Lewis R A, Schoenwald R D, Barfknecht C F
Department of Ophthalmology, University of California, Davis, Sacramento.
J Ocul Pharmacol. 1988 Fall;4(3):215-9. doi: 10.1089/jop.1988.4.215.
Aminozolamide (6-amino-2-benzothiazolesulfonamide) is a carbonic anhydrase inhibitor derived from ethoxzolamide that has been shown in gel formulation to lower IOP in rabbits, primates and humans. This study was designed to determine whether aminozolamide in suspension was also effective in lowering IOP. In separate single dose and multiple dose studies, patients with ocular hypertension were tested over 24 hours. No statistically significant drop in intraocular pressure was noted between the treated and control eye. In addition, conjunctival injection was noted in three of eleven subjects after multiple dosing. These studies suggest that retention of aminozolamide at the active site is inadequate when delivered in a suspension vehicle. In the past 10 years, efforts to develop an effective topical carbonic anhydrase inhibitor have been vigorously pursued. This has been aided by advancements in drug delivery and chemical synthesis involving molecular modification of existing carbonic anhydrase inhibitors. Various compounds have been developed that retain carbonic anhydrase inhibitory activity, penetrate the cornea and optimize the other important pharmacokinetic properties to lower intraocular pressure. One such compound, aminozolamide (6-amino-2-benzothiazolesulfonamide) is derived from ethoxzolamide. In suspension, it has been shown to lower IOP in rabbits and primates. It also has been shown to lower IOP in patients with ocular hypertension when delivered in a gel vehicle. The carbomer gel vehicle, a drug delivery system also used with pilocarpine (Pilopine HS), is used to prolong ocular contact and enhance penetration. The importance of the role of the vehicle in a topical carbonic anhydrase inhibitor has not been assessed.(ABSTRACT TRUNCATED AT 250 WORDS)
氨基唑胺（6-氨基-2-苯并噻唑磺酰胺）是一种源自乙氧唑胺的碳酸酐酶抑制剂，已证实其凝胶制剂可降低兔、灵长类动物和人类的眼压。本研究旨在确定混悬液形式的氨基唑胺是否也能有效降低眼压。在单独的单剂量和多剂量研究中，对高眼压患者进行了24小时的测试。治疗眼与对照眼之间未观察到眼压有统计学意义的下降。此外，11名受试者中有3名在多次给药后出现结膜注射现象。这些研究表明，当以混悬液载体给药时，氨基唑胺在活性部位的滞留不足。在过去10年中，人们一直在大力致力于开发一种有效的局部碳酸酐酶抑制剂。药物递送和化学合成方面的进展，包括对现有碳酸酐酶抑制剂进行分子修饰，对这一工作起到了推动作用。已经开发出了各种化合物，它们保留了碳酸酐酶抑制活性，能够穿透角膜，并优化了其他重要的药代动力学性质以降低眼压。一种这样的化合物，氨基唑胺（6-氨基-2-苯并噻唑磺酰胺）源自乙氧唑胺。在混悬液中，它已被证明可降低兔和灵长类动物的眼压。当以凝胶载体给药时，它也已被证明可降低高眼压患者的眼压。卡波姆凝胶载体是一种也与毛果芸香碱（匹鲁卡品眼膏）一起使用的药物递送系统，用于延长眼部接触时间并增强渗透。载体在局部碳酸酐酶抑制剂中的作用重要性尚未得到评估。（摘要截选至250词）
