4-WEEK SAFETY AND EFFICACY STUDY OF DORZOLAMIDE, A NOVEL, ACTIVE TOPICAL CARBONIC-ANHYDRASE INHIBITOR

Objective: To investigate the activity and local and systemic safety o f the topical carbonic anhydrase inhibitor, dorzolamide hydrochloride. Design: Four-week, double-masked, randomized, placebo-controlled, par allel, three-center study. Setting: Referral centers. Patients: Forty- eight patients with bilateral open angle glaucoma or ocular hypertensi on and intraocular pressure (IOP) greater than 22 mm Hg entered the st udy. Two of 28 patients receiving dorzolamide and two of 20 patients r eceiving placebo were withdrawn due to adverse experiences. Interventi on: Dorzolamide (2%) or placebo to each eye three times daily for 4 we eks. Main Outcome Measures: Diurnal IOP curves; ophthalmologic evaluat ions including corneal ultrasound pachymetry and endothelial cell coun t; and systemic evaluations including vital signs, blood chemistries, complete blood cell counts, urinalysis, electrocardiogram, and drug an d carbonic anhydrase activity levels in red blood cells. Results: Mean IOP at morning trough (8 AM) decreased from 27.1 mm Hg at baseline to 23.5 mm Hg on day 29 with dorzolamide (-13.3%) compared with a decrea se from 27.1 mm Hg to 26.4 mm Hg with placebo (-2.3%). Peak activity o ccurred 2 hours after administration, with IOP decreasing from 26.8 mm Hg at baseline to 21.8 mm Hg on day 29 with dorzolamide (-18.4%) vs 2 6.1 mm Hg to 25.5 (-2.4%) with placebo. Mean corneal thickness was sli ghtly increased for the dorzolamide-treated group compared with the pl acebo-treated group (0.009 mm vs 0.001 mm, respectively, P<.05) and ch anges in endothelial cell counts were similar (-24 cells/mm2vs -27 cel ls/mm2, respectively, P>.25). Mean carbonic anhydrase isoenzyme 11 act ivity in red blood cells decreased to 21% of baseline in dorzolamide-t reated patients. There were no clinically significant differences in o cular or laboratory parameters between the dorzolamide and placebo gro ups. Conclusions: Dorzolamide demonstrated significant IOP lowering ac tivity over 4 weeks. It was well tolerated and there were no clinicall y significant changes in ocular or systemic safety parameters.