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Background: Brinzolamide as a carbonic anhydrase inhibitor could be combined with other intraocular pressure (IOP) lowering drugs for glaucoma and ocular hypertension (OHT), but the efficacy was controversial. So, this study was used to assess the efficacy and safety of brinzolamide as add-on to prostaglandin analogues (PGAs) or β-blocker in treating patients with glaucoma or OHT who fail to adequately control IOP.Methods: We searched PubMed, Embase, MEDLINE, Cochrane Library, and clinicaltrials.gov from inception to October 4, 2018. Randomized controlled trials of brinzolamide as add-on to PGAs or β-blocker for glaucoma and OHT were included. Meta-analysis was conducted by RevMan 5.3 software.Results: A total of 26 trials including 5,583 patients were analyzed. Brinzolamide produced absolute reductions of IOP as an adjunctive therapy for patients with glaucoma or OHT. Brinzolamide and timolol were not significantly different in lowering IOP as add-on to PGAs (9 am: P = 0.07; 12 am: P = 0.66; 4 pm: P = 0.66). Likewise, brinzolamide was as effective as dorzolamide in depressing IOP (9 am: P = 0.59; 12 am: P = 0.94; 4 pm: P = 0.95). For the mean diurnal IOP at the end of treatment duration, there were no statistical differences in above comparisons (P > 0.05). Compared with brimonidine (b.i.d.), there was a significant reduction of IOP in brinzolamide (b.i.d.) at 9 am (P < 0.0001); however, the difference was cloudy in thrice daily subgroup (P = 0.44); at 12 am, brinzolamide (b.i.d.) was similar to brimonidine (b.i.d.) in IOP-lowering effect (P = 0.23), whereas brimonidine (t.i.d.) led to a greater effect than brinzolamide (t.i.d.) (P = 0.02). At 4 pm, brinzolamide (b.i.d.) was superior IOP-lowering effect compared with brimonidine (b.i.d.) (P = 0.0003); conversely, the effect in brinzolamide (t.i.d.) was lower than brimonidine (t.i.d.) (P < 0.0001). For the mean diurnal IOP, brinzolamide was lower in twice daily subgroup (P < 0.00001); brimonidine was lower in thrice daily subgroup (P < 0.00001). With regard to the safety, brinzolamide and dorzolamide had a higher incidence of taste abnormality; moreover, brinzolamide resulted in more frequent blurred vision; dorzolamide resulted in more frequent ocular discomfort and eye pain. Timolol resulted in more frequent blurred vision and less conjunctival hyperemia. Brimonidine resulted in more frequent ocular hyperemia. As to other adverse events (AEs) (conjunctivitis, eye pruritus, foreign body sensation in eyes, and treatment-related AEs), brinzolamide was similar to other three active comparators.Conclusions: Brinzolamide, as add-on to PGAs or β-blocker, significantly decreased IOP of patients with refractory glaucoma or OHT and the AEs were tolerable.

Background: Brinzolamide as a carbonic anhydrase inhibitor could be combined with other intraocular pressure (IOP) lowering drugs for glaucoma and ocular hypertension (OHT), but the efficacy was controversial. So, this study was used to assess the efficacy and safety of brinzolamide as add-on to prostaglandin analogues (PGAs) or β-blocker in treating patients with glaucoma or OHT who fail to adequately control IOP. Methods: We searched PubMed, Embase, MEDLINE, Cochrane Library, and clinicaltrials.gov from inception to October 4, 2018. Randomized controlled trials of brinzolamide as add-on to PGAs or β-blocker for glaucoma and OHT were included. Meta-analysis was conducted by RevMan 5.3 software. Results: A total of 26 trials including 5,583 patients were analyzed. Brinzolamide produced absolute reductions of IOP as an adjunctive therapy for patients with glaucoma or OHT. Brinzolamide and timolol were not significantly different in lowering IOP as add-on to PGAs (9 am: P = 0.07; 12 am: P = 0.66; 4 pm: P = 0.66). Likewise, brinzolamide was as effective as dorzolamide in depressing IOP (9 am: P = 0.59; 12 am: P = 0.94; 4 pm: P = 0.95). For the mean diurnal IOP at the end of treatment duration, there were no statistical differences in above comparisons (P > 0.05). Compared with brimonidine (b.i.d.), there was a significant reduction of IOP in brinzolamide (b.i.d.) at 9 am (P < 0.0001); however, the difference was cloudy in thrice daily subgroup (P = 0.44); at 12 am, brinzolamide (b.i.d.) was similar to brimonidine (b.i.d.) in IOP-lowering effect (P = 0.23), whereas brimonidine (t.i.d.) led to a greater effect than brinzolamide (t.i.d.) (P = 0.02). At 4 pm, brinzolamide (b.i.d.) was superior IOP-lowering effect compared with brimonidine (b.i.d.) (P = 0.0003); conversely, the effect in brinzolamide (t.i.d.) was lower than brimonidine (t.i.d.) (P < 0.0001). For the mean diurnal IOP, brinzolamide was lower in twice daily subgroup (P < 0.00001); brimonidine was lower in thrice daily subgroup (P < 0.00001). With regard to the safety, brinzolamide and dorzolamide had a higher incidence of taste abnormality; moreover, brinzolamide resulted in more frequent blurred vision; dorzolamide resulted in more frequent ocular discomfort and eye pain. Timolol resulted in more frequent blurred vision and less conjunctival hyperemia. Brimonidine resulted in more frequent ocular hyperemia. As to other adverse events (AEs) (conjunctivitis, eye pruritus, foreign body sensation in eyes, and treatment-related AEs), brinzolamide was similar to other three active comparators. Conclusions: Brinzolamide, as add-on to PGAs or β-blocker, significantly decreased IOP of patients with refractory glaucoma or OHT and the AEs were tolerable. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the corneal penetration of brinzolamide (BZ) nanoemulsions (NEs) and evaluate their in vitro and ex vivo irritancy potential. Twelve BZ NEs were prepared by the spontaneous emulsification method and ex vivo permeability studies were conducted using excised bovine corneas fixed onto Franz diffusion cells. To confirm the safety of the formulations for ophthalmic use, preparations were examined for potential ocular irritancy using a cell viability assay on retinal cells, the Hen's Egg Test-Chorio-Allantoic Membrane (HET-CAM) and the bovine corneal opacity-permeability (BCOP) test. Seven BZ NEs exhibited superior penetration across isolated bovine cornea compared to the marketed BZ suspension. The half maximal inhibitory concentration (IC50) values of various surfactants and oils determined using the sulforhodamine B cell viability assay on retinal cells showed that Transcutol P, Cremophor RH40 and Triacetin were the least toxic excipients and may be safely used in the eye at various concentrations. HET-CAM and BCOP tests revealed that NE6B and NE4C did not result in any irritation and were thus considered safe for ocular use. Our finding suggests that optimized NEs can be a safe and effective vehicle for ocular delivery of BZ. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the acute effects of brinzolamide, betaxolol, and latanoprost (drugs commonly used in the medical management of glaucoma) on choroidal thickness using enhanced depth imaging optical coherence tomography (EDI-OCT). Methods: Ninety healthy volunteers were evaluated in this prospective study. Participants were randomly divided into 3 groups. Brinzolamide, betaxolol, and latanoprost were administered into the left eyes of the first group (n = 30), second group (n = 30), and third group (n = 30), respectively, and artificial tear (Sodium hyaluronate) was instilled into the right eyes of all participants. Subfoveal choroidal thickness (SFCT) was measured using EDI-OCT before and 45 minutes after administration of the antiglaucomatous drops. Results: SFCT revealed a significant increase in the left eye (administered antiglaucomatous drop) in the brinzolamide (p = 0.001) and betaxolol groups (p = 0.049) and a significant increase also in the right eye (administered artificial drop) in the brinzolamide (p = 0.001) and betaxolol groups (p = 0.001). However, SFCT did not reveal a significant increase in the left eye (p = 0.213) or in the right eye (p = 0.062) in the latanoprost group. Conclusion: Brinzolamide and betaxolol caused an increase in SFCT, while latanoprost had no significant effect on SFCT. [ABSTRACT FROM AUTHOR]

In this study an inclusion complex between Brinzolamide (BRZ) and 2- Hydroxypropyl Beta Cyclodextrin (2-HP-ß- CD) was prepared and incorporated into Chitosan (CS)/Tripolyphosphate (TPP) nanogels to provide sustained release of BRZ with increased retention time in the corneal region. Further to this, an attempt was made to increase the viscosity of the prepared CS/TPP nanogels using CS/PVA (polyvinyl alcohol) biopolymer composite.BRZ, is a second line therapy for glaucoma but suffers from poor aqueous solubility leading to lesser absorption and side effects on its administration in ocular delivery. Thus by increasing the solubility and ocular retention will reduce its frequency of administration and dose followed by increases its absorption.BRZ was complexed with 2-HP-ß-CD by solvent evaporation and confirmed by FTIR, XRD and SEM. The complex was incorporated into chitosan nanogels and evaluated for in vitro drug release, ex vivo mucoadhesive and permeation studies.BRZ-2-HP-ß-CD complex (1:1 molar ratio) showed improved aqueous solubility and dissolution as compared to BRZ aqueous dispersion. Chitosan nanogels showed particle size of 219.1 ± 0.94 nm, zeta potential of +26.63 ± 0.28 mV, entrapment efficiency of 80.2837 ± 1.7635% having sustained release and following Fickian diffusion. CDNG1 exhibited 15.32 fold increases in the in vitro corneal permeability coefficient in comparison with commercial Brinolar® and exhibited mucoadhesive properties. The results imply the potential of BRZ-HP-ß-CD complex loaded Chitosan Nanogels as a novel formulation of BRZ for ocular delivery. [ABSTRACT FROM AUTHOR]

The present work was designed to investigate the antiglaucoma activity of Sesbania grandiflora (SG) aqueous leaf extract against alpha chymotrypsin induced experimental glaucoma in rabbits. The experimental increase in IOP was achieved using alpha chymotrypsin induced glaucoma model. Once the IOP was increased significantly, aqueous leaf extract of SG and standard were given topically every day into the right eye of rabbits. IOP was measured by Schiotz indentation tonometer on every alternate day till a significant reduction of IOP was observed. The results were compared with standard 0.1% brinzolamide. A significant increase in IOP was observed on the 7th day after inducing glaucoma. Significant reduction of IOP was observed on the 6th day after giving plant extract when compared with the standard. The results show that the leaf extract showed significant occulohypotensive activity and this effect was comparable to the standard brinzolamide. Further investigation into the mechanism of action and isolation of compounds which are responsible for antiglaucoma activity is to be established. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The aim of this study is to investigate the potential of D-alpha-tocopheryl poly (ethylene glycol 1000) succinate (TPGS) modified nanoliposomes as an ophthalmic delivery system of brinzolamide (Brz) for glaucoma treatment. The Brz loaded nanoliposomes containing TPGS (T-LPs/Brz) were firstly developed by a thin-film dispersion method. The average particle size was 96.87 ± 4.43 nm. The entrapment efficiency of the Brz was 95.41 ± 3.03% and the drug loading was 4.00 ± 0.13%. T-LPs/Brz exhibited obvious sustained release of Brz; in stark contrast to the normal liposomes of Brz (LPs/Brz) and the commercial formulation AZOPT® (Brz ophthalmic suspension, Brz-Sus). Enhanced trans-corneal transport of Brz was achieved with T-LPs/Brz. Compared with both Brz-Sus and LPs/Brz, the apparent permeability coefficient (P app) of T-LPs/Brz was 10.2 folds and 1.38 folds higher, respectively. Moreover, T-LPs/Brz extended the cornea residence of Brz. White New Zealand rabbits treated with T-LPs/Brz had 3.18 folds and 1.57 folds Brz concentration 2 h after treatment than Brz-Sus and LPs/Brz, respectively. Further pharmacodynamic studies showed that T-LPs/Brz maintained an effective intraocular pressure (IOP) reduction from 3 h to 11 h after administration, while Brz-Sus and LPs/Brz presented effective IOP decreases from 3 h to 6 h and 3 h to 8 h respectively. The preliminary safety evaluation demonstrated that T-LPs/Brz had no significant side effects; specifically, no cornea damage and eye irritation. All the results indicated that TPGS modified nanoliposomes were a promising ocular delivery carriers for Brz to treat glaucoma. As such, T-LPs/Brz might be worthy of further translational study. [ABSTRACT FROM AUTHOR]

The two β-carbonic anhydrases (CAs, EC 4.2.1.1) recently cloned and purified from the ascomycete fungus Sordaria macrospora, CAS1 and CAS2, were investigated for their inhibition with a panel of 39 aromatic, heterocyclic, and aliphatic sulfonamides and one sulfamate, many of which are clinically used agents. CAS1 was efficiently inhibited by tosylamide, 3-fluorosulfanilamide, and 3-chlorosulfanilamide (KIs in the range of 43.2-79.6 nM), whereas acetazolamide, methazolamide, topiramate, ethoxzolamide, dorzolamide, and brinzolamide were medium potency inhibitors (KIs in the range of 360-445 nM). CAS2 was less sensitive to sulfonamide inhibitors. The best CAS2 inhibitors were 5-amino-1,3,4-thiadiazole-2-sulfonamide (the deacetylated acetazolamide precursor) and 4-hydroxymethyl-benzenesulfonamide, with KIs in the range of 48.1-92.5 nM. Acetazolamide, dorzolamide, ethoxzolamide, topiramate, sulpiride, indisulam, celecoxib, and sulthiame were medium potency CAS2 inhibitors (KIs of 143-857 nM). Many other sulfonamides showed affinities in the high micromolar range or were ineffective as CAS1/2 inhibitors. Small changes in the structure of the inhibitor led to important differences of the activity. As these enzymes may show applications for the removal of anthropically generated polluting gases, finding modulators of their activity may be crucial for designing environmental-friendly CO2 capture processes. [ABSTRACT FROM AUTHOR]

Introduction: To simplify the medical treatment of glaucoma for patients on multiple drops by introducing brinzolamide/brimonidine tartrate fixed combination (BBFC) ophthalmic suspension 1%/0.2% (SIMBRINZA®; Alcon Laboratories, Inc., Fort Worth, TX, USA) to the drop regimen and to establish its efficacy. To demonstrate that fixed combination (FC) therapies are associated with improvements in treatment adherence and persistence with reduced exposure to preservative-related ocular surface problems.Methods: Retrospective study: 76 patients were identified as taking BBFC following a switch in treatment regimen. Intraocular pressure (IOP) prior to and 2-17.5 months (average 5.4 months) after the introduction of BBFC was measured. The change in the average number of bottles used per eye was recorded. The rate of adverse effects (AEs) of BBFC was recorded. A two-tailed paired sample t test was used to compare IOP prior to and after the introduction of BBFC for each eye.Results: Mean change in IOP after BBFC introduction BBFC: − 2.76 mmHg (p < 0.0001). BBFC intolerance: 13%. On average there was a 0.24 reduction in the number of bottles of IOP-lowering medication used per eye (p < 0.0064).Conclusion: A switch to BBFC in the drop regimen is associated with a significant drop in IOP with reduced drop burden. Instead of a third IOP-lowering medication and bottle, a practitioner should consider using BBFC + prostaglandin analogue/FC drop for effective IOP control, reduced drop burden, reduced preservative load and increased likelihood of adherence. This study promotes the concept that any treatment should principally be assessed from the patients’ perspective and quality of life. [ABSTRACT FROM AUTHOR]

Keywords: allergic contact dermatitis; brinzolamide; case report; glaucoma; periocular; Simbrinza EN allergic contact dermatitis brinzolamide case report glaucoma periocular Simbrinza 274 276 3 03/22/21 20210401 NES 210401 CASE REPORT A 52-year-old woman was referred to our Contact Eczema Department with right-sided, chronic, periocular eczema that had developed over the past 12 months. DISCUSSION Ophthalmic topical drug preparations include active ingredients and excipients. [Extracted from the article]