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 1.5-3.9 μM drug in the retinas of treated eyes and 1.3-3.7 μM drug in retinas of the fellow eye. After allowance was made for the blood content of retinas (1.4-13%) and drug contained in whole blood due to systemic absorption, little (<1.4 μM) 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 μM) 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.