Disease relevance of Brinzolamide

• Dorzolamide and brinzolamide are two topical CA inhibitors which are currently available to treat ocular hypertension and/or glaucoma [1].
• The efficacy and safety of brinzolamide 1% ophthalmic suspension (Azopt, Befardin) as a primary therapy in patients with open-angle glaucoma or ocular hypertension . Brinzolamide Primary Therapy Study Group [2].
• Topical brinzolamide and metabolic acidosis [3].
• Corneal edema in glaucoma patients after the addition of brinzolamide 1% ophthalmic suspension [4].
• There was no significant difference for any adverse event between groups (p>0.05), with the most common side effect being conjunctival hyperemia in 15/97 (16%) brinzolamide and 6/95 (6%) timolol treated patients (p=0.06) [5].

High impact information on Brinzolamide

• Some clinically used compounds, such as acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, topiramate, sulpiride, and indisulam, or the orphan drug benzolamide, showed effective hCA VI inhibitory activity, with inhibition constants of 0.8-79 nM [6].
• Structures of murine carbonic anhydrase IV and human carbonic anhydrase II complexed with brinzolamide: molecular basis of isozyme-drug discrimination [7].
• Binding interactions observed for brinzolamide rationalize the generally weaker affinity of inhibitors used in glaucoma therapy toward CAIV compared with CAII [7].
• Brinzolamide 1% versus apraclonidine 0.5% to prevent intraocular pressure elevation after neodymium:YAG laser posterior capsulotomy [8].
• A randomized, investigator-masked, 4-week study comparing timolol maleate 0.5%, brinzolamide 1%, and brimonidine tartrate 0.2% as adjunctive therapies to travoprost 0.004% in adults with primary open-angle glaucoma or ocular hypertension [9].

Chemical compound and disease context of Brinzolamide

• Adjunctive therapy with brinzolamide 1% ophthalmic suspension (Azopt) in patients with open-angle glaucoma or ocular hypertension maintained on timolol therapy [10].
• Ocular hypotensive efficacy and safety of brinzolamide ophthalmic suspension 1% added to travoprost ophthalmic solution 0.004% therapy in patients with openangle glaucoma or ocular hypertension [11].
• PATIENTS AND METHODS: Fourteen patients with open angle glaucoma (OAG) or ocular hypertension (OH) who had been using latanoprost 0.005% for more than 6 months were initiated on adjunctive brinzolamide therapy [12].

Biological context of Brinzolamide

• Structure-activity relationships rationalize affinity trends observed during the development of brinzolamide (Azopt), the newest carbonic anhydrase inhibitor approved for the treatment of glaucoma [13].
• CONCLUSIONS: Topical ocular CAI treatment for 1 week with either brinzolamide or dorzolamide significantly reduced IOP and significantly increased ONH blood flow in tranquilized Dutch-belted rabbits, while eliciting minimal systemic acid-base balance disturbances [14].
• OBJECTIVES: Using a three-way crossover study design, we compared the effects of brinzolamide 2%, dorzolamide 2%, and placebo (vehicle) on microvascular optic nerve head (ONH) blood flow, intraocular pressure (IOP), blood pressure, heart rate, and acid-base balance in nine acepromazine-tranquilized Dutch-belted rabbits [14].
• These characteristics, along with good ocular bioavailability, make brinzolamide maximally effective in lowering intraocular pressure (IOP) by locally inhibiting CA-II in the ciliary processes and suppressing aqueous humor secretion [15].
• Neither brinzolamide nor placebo changed visual field global indices after treatment [16].

Anatomical context of Brinzolamide

• Results of studies in animals show that brinzolamide has promise for increasing blood flow to the optic nerve head; however, this requires further assessment in the clinic [15].
• Brinzolamide therapy alone resulted in a significant reduction of AVP compared to baseline (p<0.05), while peripapillary retinal vessels diameters remained unaffected [16].
• In this study, the various antiglaucoma drugs including betaxolol, timolol, levobunolol, carteolol, brimonidine, dipivefrin, dorzolamide, brinzolamide, latanoprost, unoprostone, and pilocarpine were used to investigate the effects of cellular cytotoxicity in cultured bovine corneal endothelial cells [17].

Associations of Brinzolamide with other chemical compounds

• Four to 6 hours postoperatively, the acetazolamide group (P=.002) and brinzolamide group (P=.001) had significantly lower IOP than the control group [18].
• PURPOSE: To compare the effectiveness of brinzolamide 1% (Azopt, Befardin) and brimonidine 0.2% (Alphagan) with a placebo in preventing an early increase in intraocular pressure (IOP) after phacoemulsification [19].
• CONCLUSION: Both travoprost and brinzolamide significantly lowered IOP after small incision phacoemulsification cataract surgery within the first 24 h without any side effect [20].
• CONCLUSIONS: In terms of intraocular pressure reduction, brinzolamide 1% twice daily was equivalent to dorzolamide 2% twice daily, each added to timolol 0.5% twice daily, but brinzolamide produced significantly less ocular burning and stinging [21].
• The topical carbonic anhydrase inhibitors brinzolamide (Azopt; Alcon, at $0.96/day) and dorzolamide (Trusopt; Merck, at $1.02/day) were dosed three times daily and were similar on a cost-per-day basis [22].

Gene context of Brinzolamide

• The inhibition of the tumor-associated transmembrane carbonic anhydrase IX (CA IX) isozyme has been investigated with a series of aromatic and heterocyclic sulfonamides, including the six clinically used derivatives acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide and brinzolamide [23].

Analytical, diagnostic and therapeutic context of Brinzolamide

• Brinzolamide has been shown by the laser Doppler flowmetry technique to improve blood flow to the optic nerve head in pigmented rabbits after topical administration, without producing an increase of blood pCO2, indicating a potential for a local vasodilatory effect involving the optic nerve head circulation [15].
• CONCLUSION: Brinzolamide 1% and apraclonidine 0.5% given prophylactically before Nd:YAG laser capsulotomy were effective in preventing IOP spikes after treatment [8].
• This was substantiated in clinical trials, which showed that twice-daily brinzolamide provides as significant an IOP reduction as three-times-daily brinzolamide or dorzolamide in a relatively high percentage of patients [15].
• METHODS: One hundred fifteen patients who had Nd:YAG laser posterior capsulotomy for posterior capsule opacification were prospectively randomized to receive brinzolamide 1% (57 patients) or apraclonidine 0.5% (58 patients) approximately 1 hour before laser surgery [8].
• Intraocular pressures were measured by pneumatonometry and aqueous flow was determined by fluorophotometry before and after three twice-daily drops of 1% brinzolamide to both eyes per monkey and after similar treatment to one eye per rabbit [24].

References