Lee D Y, Schoenwald R D, Barfknecht C F
Liquid Formulation Section, Wyeth-Ayerst Research, Rouses Point, New York.
J Ocul Pharmacol. 1992 Fall;8(3):247-65. doi: 10.1089/jop.1992.8.247.
6-Hydroxyethoxy-2-benzothiazolesulfonamide (compound 1), 6-hydrogen-2-benzothiazolesulfonamide (compound 2) and ethoxzolamide (compound 3) are carbonic anhydrase inhibitors, of which only compound 1 is active in lowering intraocular pressure when administered to the rabbit eye. They were compared for potency by inhibiting carbonic anhydrase I (CAase I) using the pH stat procedure. No differences were detected. Binding affinity and number of binding sites were identical; only a single binding site was operative. 14C-labelled compound 1 was used to measure the presence of an ocular metabolite which ranged from 17 to 57% in cornea, iris/ciliary body and aqueous humor. By maintaining drug solutions on either the corneal or conjunctival/scleral surfaces of the eye of anesthetized rabbits for 120 minutes, steady state concentrations of compounds 1-3 were determined in cornea, aqueous humor and iris/ciliary body. It was concluded that compound 1 penetrated both routes equally well and also accumulated at the active site in considerably higher concentrations than compounds 2 and 3. Compounds 2 and 3 did not accumulate in the iris/ciliary body nor did compound 3 penetrate the conjunctival/scleral route very well, approximately 5-20 fold lower than from the corneal route.
6-羟基乙氧基-2-苯并噻唑磺酰胺（化合物1）、6-氢-2-苯并噻唑磺酰胺（化合物2）和乙氧唑胺（化合物3）均为碳酸酐酶抑制剂，其中仅化合物1在对兔眼给药时具有降低眼压的活性。通过使用pH计程序抑制碳酸酐酶I（CAase I）来比较它们的效力。未检测到差异。结合亲和力和结合位点数量相同；只有一个结合位点起作用。使用14C标记的化合物1来测量眼内代谢物的存在情况，其在角膜、虹膜/睫状体和房水中的含量为17%至57%。通过在麻醉兔眼的角膜或结膜/巩膜表面维持药物溶液120分钟，测定了化合物1 - 3在角膜、房水和虹膜/睫状体中的稳态浓度。得出的结论是，化合物1通过两种途径的渗透效果相同，并且在活性部位的积累浓度比化合物2和3高得多。化合物2和3在虹膜/睫状体中不积累，化合物3通过结膜/巩膜途径的渗透效果也不佳，比通过角膜途径低约5 - 20倍。
