title: Biopharmaceutical explanation for the topical activity of 6-hydroxyethoxy-2-benzothiazolesulfonamide in the rabbit eye.
abstract: 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.
authors.affiliation: Liquid Formulation Section, Wyeth-Ayerst Research, Rouses Point, New York.
authors.forename: D Y
authors.initials: DY
authors.lastname: Lee
authors.forename: R D
authors.initials: RD
authors.lastname: Schoenwald
authors.forename: C F
authors.initials: CF
authors.lastname: Barfknecht
mesh_terms: D000287:Administration, Topical; D000818:Animals; D052160:Benzothiazoles; D002257:Carbonic Anhydrase Inhibitors / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005016:Ethoxzolamide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005123:Eye / Q000378:metabolism*; D005260:Female; D008297:Male; D011485:Protein Binding; D011817:Rabbits; D013449:Sulfonamides / Q000493:pharmacokinetics; D013844:Thiazoles / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D052160:Benzothiazoles; D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D013844:Thiazoles; C078551:2-benzothiazolesulfonamide; C043694:6-hydroxyethoxzolamide; D005016:Ethoxzolamide