title: Sulfonamides do not reach the retina in therapeutic amounts after topical application to the cornea.
abstract: Retinal drug concentrations were measured in treated and fellow eyes following topical administration of two potent and permeable carbonic anhydrase inhibitors, MK-927 and trifluoromethanesulfonamide (CF3SO2NH2) in the rabbit. Administration of 2 or 5 drops 2% MK-927 or 2% CF3SO2NH2 gave at 1 hr 1.5-9 microM drug in the retinas of treated eyes and 1.3-3.7 microM drug in the retinas of the fellow eye. After allowance was made for the blood content of the retinas (1.4-13%) and drug contained in whole blood due to systemic absorption, little (< 1.4 microM) or no net accumulation in retina could be documented. In a second series of experiments animals were treated with 5 mg/kg i.v. of either MK-927 or CF3SO2NH2 in order to fully saturate red cell carbonic anhydrase prior to topical administration of drug. For MK-927 there was a net accumulation in retina 3 hrs following topical administration in both treated and fellow eyes (3-4 microM) which was approximately 1/4 the concentration in plasma, suggesting that some drug had permeated the blood-retinal barrier. Similar results were obtained with CF3SO2NH2, giving no difference between treated and fellow eyes; retinal concentrations were approximately 90% of plasma concentrations. These results suggest that there is no direct access to retina by posterior or uveoscleral drainage of topically applied sulfonamides other than systemically absorbed drug.
authors.affiliation: University of Florida College of Medicine, Department of Pharmacology and Therapeutics, Gainesville, USA.
authors.forename: C W
authors.initials: CW
authors.lastname: Conroy
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D003315:Cornea / Q000187:drug effects*; D008297:Male; D011817:Rabbits; D012160:Retina / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D013876:Thiophenes; C057921:sezolamide