Dose-Response Evaluation of the Ocular Hypotensive Effect of Brinzolamide Ophthalmic Suspension (Azopt^®)

Abstract 

Brinzolamide is a novel carbonic anhydrase inhibitor that elicits an ocular hypotensive effect when instilled topically. A multicenter, double-masked, placebo-controlled, parallel trial was conducted to evaluate the optimal intraocular pressure (IOP)–lowering concentration and ocular tolerability of topically administered brinzolamide (0.3%, 1%, 2%, and 3%) in patients with primary open-angle glaucoma or ocular hypertension. After a washout phase, patients were administered brinzolamide or placebo twice daily for 2 weeks. The IOP was measured on days 8 and 15 at 8:00 a.m., and then 2, 4, 8, and 12 hours after dosing, and these measurements were compared with IOP values obtained at the corresponding times during an off-therapy diurnal baseline. All concentrations of brinzolamide produced significantly greater (P < 0.005) mean percent IOP reductions and mean IOP reductions compared with placebo. Mean percent IOP changes (mean IOP changes) from baseline for brinzolamide 0.3%, 1%, 2%, and 3% were −11.3% (−3.0 mm Hg), −16.1% (−4.3 mm Hg), −16.1% (−4.4 mm Hg), and −15.4% (−4.2 mm Hg), respectively, when pooled over visit and visit time. Comparisons between concentrations demonstrated that the mean percent IOP reduction for brinzolamide 1.0% was significantly greater than that for the 0.3% concentration (P < 0.03), with no difference in efficacy between the 1%, 2%, and 3% concentrations. The incidence of adverse events was dose-dependent, and those related to therapy were usually mild and resolved without treatment. Blurred vision, ocular discomfort, and abnormal taste were the most frequently reported adverse events. Based on these findings, the optimal IOP-lowering concentration of brinzolamide was 1%. When administered twice daily, brinzolamide 1% was well tolerated by patients with primary open-angle glaucoma or ocular hypertension.

Keywords:  Azopt^®, brinzolamide, carbonic anhydrase inhibitor, open-angle glaucoma