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BACKGROUND: Brinzolamide (BRI) suspensions are used for the treatment of glaucoma; however, sufficient drug delivery to the target tissue after eye drop administration is hampered by poor solubility. To address this issue, we focused on nanocrystal technology, which is expected to improve the bioavailability of poor-solubility drugs, and investigated the effect of BRI nanocrystal formulations on corneal permeability and intraocular pressure (IOP)-reducing effect. METHODS: BRI nanocrystal formulations were prepared by the wet-milling method with beads and additives. The particle size was measured by NANOSIGHT LM10, and the morphology was determined using a scanning probe microscope (SPM-9700) and a scanning electron microscope (SEM). Corneal permeability was evaluated in vitro using a Franz diffusion cell with rat corneas and in vivo using rabbits, and the IOP-reducing effect was investigated using a rabbit hypertensive model. RESULTS: The particle size range for prepared BRI nanocrystal formulation was from 50 to 300 nm and the mean particle size was 135 ± 4 nm. The morphology was crystalline, and the nanoparticles were uniformly dispersed. In the corneal permeability study, BRI nanocrystallization exhibited higher corneal permeability than non-milled formulations. This result may be attributed to the increased solubility of BRI by nanocrystallization and the induction of energy-dependent endocytosis by the attachment of BRI nanoparticles to the cell membrane. Furthermore, the addition of tyloxapol to BRI nanocrystal formulation further improved the intraocular penetration of BRI and showed a stronger IOP-reducing effect than the commercial product. CONCLUSIONS: The combination of BRI nanocrystallization and tyloxapol is expected to be highly effective in glaucoma treatment and a useful tool for new ophthalmic drug delivery.
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BACKGROUND: Glaucoma treatment often involves multi-drug regimens, which can lead to poor adherence and side effects. Fixed-dose combinations aim to improve adherence and reduce side effects compared to traditional therapies. This study aimed to compare the prevalence and clinical characteristics of ocular allergy in glaucoma patients using brinzolamide 1.0%/brimonidine 0.2% fixed combination (BBFC), with and without concurrent ß-blocker. METHODS: Of these, 176 patients used a ß-blocker concurrently, whereas 96 patients did not. Allergy prevalence, allergy type, and allergy occurrence time were compared between the concurrent and non-concurrent ß-blocker-usage groups. Ocular allergies were classified and evaluated using Kaplan-Meier survival analysis. RESULTS: Allergy prevalence was 10.23% and 15.63% (p = 0.193), whereas allergy occurrence time was 15.92 ± 13.80 months and 6.26 ± 6.20 months (p = 0.04) in the concurrent and non-concurrent ß-blocker-usage groups, respectively. Kaplan-Meier survival analysis indicated that half of the allergies in the concurrent ß-blocker-usage group occurred within 12.5 months, with the BBFC discontinuation rate gradually increasing up to 36 months. Contrarily, half of the allergies in the non-concurrent ß-blocker-usage group occurred within 3.3 months, with a rapid increase in BBFC discontinuation rate the first 6 months. Intergroup differences in allergy types were significant (p = 0.015). Among all patients with allergy, the average allergy occurrence time of blepharoconjunctivitis, papillary conjunctivitis, and follicular conjunctivitis was 12.52, 9.53, and 13.23 months, respectively. Follicular conjunctivitis tended to occur later than papillary conjunctivitis (p = 0.042). In the concurrent ß-blocker-usage group, follicular conjunctivitis was the most prevalent allergy type (61.1%), whereas papillary conjunctivitis was the most common (66.7%) in in the non-concurrent ß-blocker-usage group. CONCLUSIONS: Concurrent use of ß-blocker with BBFC decreases allergy prevalence, delays allergy onset, and predominantly results in follicular conjunctivitis, thereby facilitating longer treatment duration. Understanding these characteristics of allergy in BBFC users is useful to manage patients and improve treatment adherence. This study provides insights into the role of ß-blockers in modulating ocular allergy in BBFC-treated glaucoma patients, highlighting implications for clinical practice and patient education.
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Antagonistas Adrenérgicos beta , Tartrato de Brimonidina , Combinación de Medicamentos , Glaucoma , Soluciones Oftálmicas , Sulfonamidas , Tiazinas , Humanos , Masculino , Femenino , Estudios Retrospectivos , Tartrato de Brimonidina/administración & dosificación , Tartrato de Brimonidina/uso terapéutico , Tartrato de Brimonidina/efectos adversos , Anciano , Antagonistas Adrenérgicos beta/uso terapéutico , Antagonistas Adrenérgicos beta/administración & dosificación , Tiazinas/administración & dosificación , Tiazinas/uso terapéutico , Tiazinas/efectos adversos , Persona de Mediana Edad , Prevalencia , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Glaucoma/epidemiología , Glaucoma/tratamiento farmacológico , Hipersensibilidad a las Drogas/epidemiología , Inhibidores de Anhidrasa Carbónica/administración & dosificación , Inhibidores de Anhidrasa Carbónica/uso terapéutico , Antihipertensivos/uso terapéutico , Antihipertensivos/administración & dosificación , Quimioterapia Combinada , Presión Intraocular/fisiología , Presión Intraocular/efectos de los fármacos , Anciano de 80 o más AñosRESUMEN
Purpose: To compare the efficacy of Brinzolamide-Brimonidine (BB) (1%+0.2%) with the gold standard Latanoprost-Timolol (LT) (0.005%+0.5%) in treating primary open-angle glaucoma (POAG) and ocular hypertension (OHT). Methods: A 1-year prospective study, spanning from May 2022 to May 2023, conducted at a tertiary eye-care hospital. Participants, aged 40-60, with a baseline intraocular pressure (IOP) >21 mm Hg, requiring a >30% reduction, were enrolled. Group A (n = 100) received BB, and Group B (n = 100) received LT. Outcomes were assessed at 1 month (IOP difference from baseline), 3 and 6 months (mean diurnal variations). Results: The mean age at presentation was 55.5 ± 4.5 years in Group A and 54.7 ± 4.2 years in Group B. At 1 month, Group A exhibited a mean IOP of 18.7 mm Hg, while Group B had 17.6 mm Hg, with no statistically significant difference (P = 0.53). No significant diurnal variation was observed in either group (P = 0.07). Target pressure was achieved in 88% of patients in Group A and slightly higher at 92% in Group B. Moreover, no serious side effects were reported, and compliance was higher in Group B (98%) compared to Group A (96%). Conclusion: Although LT showed slightly better and sustained IOP reduction, the difference was not statistically significant. Both BB and LT demonstrated comparable outcomes for managing POAG and OHT.
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Antihipertensivos , Tartrato de Brimonidina , Glaucoma de Ángulo Abierto , Presión Intraocular , Latanoprost , Hipertensión Ocular , Sulfonamidas , Timolol , Humanos , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Persona de Mediana Edad , Presión Intraocular/efectos de los fármacos , Hipertensión Ocular/tratamiento farmacológico , Latanoprost/administración & dosificación , Latanoprost/uso terapéutico , Latanoprost/farmacología , Tartrato de Brimonidina/administración & dosificación , Tartrato de Brimonidina/uso terapéutico , Tartrato de Brimonidina/farmacología , Tartrato de Brimonidina/efectos adversos , Masculino , Femenino , Estudios Prospectivos , Timolol/administración & dosificación , Timolol/uso terapéutico , Timolol/efectos adversos , Antihipertensivos/administración & dosificación , Antihipertensivos/uso terapéutico , Antihipertensivos/efectos adversos , Antihipertensivos/farmacología , Adulto , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , Sulfonamidas/efectos adversos , Sulfonamidas/farmacología , Tiazinas/administración & dosificación , Tiazinas/uso terapéutico , Tiazinas/efectos adversos , Combinación de Medicamentos , Resultado del Tratamiento , Soluciones Oftálmicas/administración & dosificaciónRESUMEN
The aim of this work to study the feasibility of using phospholipid free vesicles with positive charge inducer in a slowly dissolving polymer ocular insert to successfully control intraocular pressure (IOP) for an extended period. Brinzolamide (BRNZ) was chosen as a model drug and a full factorial design was assembled to investigate the drug loading effect, ratio of cholesterol to fatty moiety and the type of the fatty moiety used on the vesicle size and entrapment efficiency. Linear regression models were constructed, and optimization of the formulation compositions yielded two formulae with palmitic acid as a negatively charged vesicles and cetrimide positively charged vesicles. Both formulae were studied in term of permeation efficiency through bovine corneal membranes. Positively charged vesicles although it didn't achieve the highest flux and cumulative amount permeated per unit surface area in the experiment time course, it achieved the highest retention of drug inside the corneal tissue, so it was chosen to be incorporated in a slowly dissolving polymer ocular insert. The insert was evaluated in term content, physical evaluation, and release properties. In vivo evaluation of the casted ocular inserts was conducted in male albino rabbits against market eye drop product and IOP readings were collected for 48 hours. The positively charged sterosomes containing BRNZ and formulated in polymer ocular inserts achieved extended control of IOP of the test animals compared to the market product.
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Córnea , Presión Intraocular , Fosfolípidos , Sulfonamidas , Tiazinas , Animales , Conejos , Tiazinas/administración & dosificación , Tiazinas/farmacocinética , Tiazinas/química , Sulfonamidas/administración & dosificación , Sulfonamidas/farmacocinética , Sulfonamidas/química , Masculino , Fosfolípidos/química , Presión Intraocular/efectos de los fármacos , Córnea/metabolismo , Córnea/efectos de los fármacos , Administración Oftálmica , Bovinos , Inhibidores de Anhidrasa Carbónica/administración & dosificación , Inhibidores de Anhidrasa Carbónica/farmacocinética , Inhibidores de Anhidrasa Carbónica/química , Tamaño de la Partícula , Nanopartículas/químicaRESUMEN
Aim: This study aims to explore potential of transniosomes, a hybrid vesicular system, as ocular drug-delivery vehicle. Materials & methods: Thin-film hydration technique was used to fabricate brinzolamide-loaded transniosomes (BRZ-TN) and optimized using Box-Behnken design, further exhaustively characterized for physicochemical evaluations, deformability, drug release, permeation and preclinical evaluations for antiglaucoma activity. Results: The BRZ-TN showed ultradeformability (deformability index: 5.71), exhibiting sustained drug release without irritation (irritancy score: 0) and high permeability compared with the marketed formulation or free drug suspension. The extensive in vivo investigations affirmed effective targeted delivery of transniosomes, with brinzolamide reducing intraocular pressure potentially. Conclusion: Our findings anticipated that BRZ-TN is a promising therapeutic nanocarrier for effectively delivering cargo to targeted sites by crossing corneal barriers.
[Box: see text].
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Córnea , Glaucoma , Liposomas , Permeabilidad , Sulfonamidas , Tiazinas , Córnea/metabolismo , Córnea/efectos de los fármacos , Animales , Sulfonamidas/química , Sulfonamidas/farmacología , Glaucoma/tratamiento farmacológico , Liposomas/química , Tiazinas/química , Tiazinas/farmacología , Liberación de Fármacos , Humanos , Presión Intraocular/efectos de los fármacos , Inhibidores de Anhidrasa Carbónica/química , Inhibidores de Anhidrasa Carbónica/farmacología , Portadores de Fármacos/química , Conejos , Sistemas de Liberación de Medicamentos , MasculinoRESUMEN
The intricate structure of the eye poses difficulties in drug targeting, which can be surmounted with the help of nanoformulation strategies. With this view, brinzolamide nanosponges (BNS) were prepared using the emulsion solvent evaporation technique and optimized via Box-Behnken statistical design. The optimized BNS were further incorporated into a poloxamer 407 in situ gel (BNS-ISG) and evaluated. The optimized BNS showed spherical morphology, entrapment efficiency of 83.12 ± 1.2 % with particle size of 114 ± 2.32 nm and PDI of 0.11 ± 0.01. The optimized BNS-ISG exhibited a pseudoplastic behavior and depicted a gelling temperature and gelation time of 35 ± 0.5 °C and 10 ± 2 s respectively. In-vitro release and ex- vivo permeation studies of BNS-ISG demonstrated a sustained release pattern as compared to Brinzox®. Additionally, the HET-CAM and in vitro cytotoxicity studies (using SIRC cell line) ensured that the formulation was non-irritant and nontoxic for ophthalmic delivery. The in vivo pharmacodynamic study using rabbit model depicted that BNS-ISG treatment significantly lowers the intra ocular pressure for prolonged period of time when compared with Brinzox®. In conclusion, the BNS-ISG is an efficient and scalable drug delivery system with significant potential as the targeted therapy of posterior segment eye diseases.
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Sistemas de Liberación de Medicamentos , Tiazinas , Animales , Conejos , Sulfonamidas/química , Tiazinas/química , Ojo , Tamaño de la PartículaRESUMEN
The research work aimed to develop a robust sustained release biocompatible brinzolamide (BRZ)-loaded ocular inserts (MeltSerts) using hot-melt extrusion technology with enhanced solubility for glaucoma management. A 32 rotatable central composite design was employed for the optimization of the MeltSerts to achieve sustained release. The effect of two independent factors was examined: Metolose® SR 90SH-100000SR (HPMC, hydroxypropyl methyl cellulose) and Kolliphor® P 407 (Poloxamer 407, P407). The drug release (DR) of BRZ at 0.5 h and 8 h were adopted as dependent responses. The factorial analysis resulted in an optimum composition of 50.00 % w/w of HPMC and 15.00 % w/w of P407 which gave % DR of 9.11 at 0.5 h and 69.10 at 8 h. Furthermore, molecular dynamic simulations were performed to elucidate various interactions between BRZ, and other formulation components and it was observed that BRZ showed maximum interactions with HPC and HPMC with an occupancy of 92.82 and 52.87 %, respectively. Additionally, molecular docking studies were performed to understand the interactions between BRZ and mucoadhesive polymers with ocular mucin (MUC-1). The results indicated a docking score of only -5.368 for BRZ alone, whereas a significantly higher docking score was observed for the optimized Meltserts -6.977, suggesting enhanced retention time of the optimized MeltSerts. SEM images displayed irregular surfaces, while EDS analysis validated uniform BRZ distribution in the optimized formulation. The results of the ocular irritancy studies both ex vivo and in vivo demonstrated that MeltSerts are safe for ocular use. The results indicate that the developed MeltSerts Technology has the potential to manufacture ocular inserts with cost-effectiveness, one-step processability, and enhanced product quality. Nonetheless, it also offers a once-daily regimen, consequently decreasing the dosing frequency, preservative exposure, and ultimately better glaucoma management.
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Glaucoma , Simulación de Dinámica Molecular , Humanos , Preparaciones de Acción Retardada/uso terapéutico , Simulación del Acoplamiento Molecular , Glaucoma/tratamiento farmacológico , Solubilidad , TecnologíaRESUMEN
PURPOSE: A brimonidine tartrate 0.1%/brinzolamide 1% fixed-dose combination (BBFC) was recently approved for glaucoma and ocular hypertension treatment in Japan. We investigated the efficacy and safety of BBFC used concomitantly with prostaglandin analogs (PG) or a PG/beta-blocker fixed-dose combination (PG/beta FC). STUDY DESIGN: This was a prospective, open-label, multicenter study. PATIENTS AND METHODS: We enrolled Japanese patients with open-angle glaucoma. BBFC (Ailamide) was concomitantly administered to either the PG or the PG/beta FC group, and intraocular pressure (IOP) and safety were evaluated at 4 and 12 weeks. The groups were stratified into low and high IOP baseline groups based on the median baseline IOP. RESULTS: We enrolled 100 patients, 91 of whom completed the 12-week follow-up. The mean ages were 67.1 and 65.7 years in the PG group (n = 45, baseline IOP of 15.7 ± 2.3 mmHg) and the PG/beta FC group (n = 46, baseline IOP of 16.3 ± 2.3 mmHg), respectively. After BBFC administration, IOPs at 4 and 12 weeks were 13.0 ± 2.0 and 13.0 ± 2.6 mmHg (P < 0.0001) in the PG group, respectively, and 13.7 ± 2.4 and 13.7 ± 2.2 mmHg (P < 0.0001) in the PG/beta FC group, respectively. IOP decreased by - 2.0 ± 1.8 mmHg (P < 0.0001) and -1.9 ± 1.4 mmHg (P < 0.0001) in the low baseline PG group (14.1 mmHg) and low baseline PG/beta FC group (14.8 mmHg) at 12 weeks, respectively. Sixteen adverse events were identified, all of which were common and did not affect visual acuity. CONCLUSIONS: BBFC can be used concomitantly with PG or PG/beta FC to reduce IOP without serious complications.
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Glaucoma de Ángulo Abierto , Hipertensión Ocular , Humanos , Tartrato de Brimonidina , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Estudios Prospectivos , Pueblos del Este de Asia , Antihipertensivos/uso terapéutico , Presión Intraocular , Hipertensión Ocular/tratamiento farmacológico , Prostaglandinas Sintéticas/uso terapéutico , Timolol , Combinación de MedicamentosRESUMEN
Brinzolamide is an effective carbonic anhydrase inhibitor widely used in glaucoma therapy but limits its application due to inadequate aqueous solubility and permeability. The aim of the present research work is the development and characterization of brinzolamide-loaded ultradeformable bilosomes to enhance the corneal permeation of the drug. These ultradeformable bilosomes were prepared by ethanol injection method and evaluated for physicochemical properties, particle size, morphology, drug release, ultra-deformability, corneal permeation, and irritation potential. The optimized formulation exhibited an average particle size of 205.4 ± 2.04 nm with mono-dispersity (0.109 ± 0.002) and showed entrapment efficiency of 75.02 ± 0.017%, deformability index of 3.91, and release the drug in a sustained manner. The brinzolamide-loaded ultradeformable bilosomes released 76.29 ± 3.77% of the drug in 10 h that is 2.25 times higher than the free drug solution. The bilosomes were found non-irritant to eyes with a potential irritancy score of 0 in Hen's egg-chorioallantoic membrane assay. Brinzolamide-loaded ultradeformable bilosomes showed 83.09 ± 5.1% of permeation in 6 h and trans-corneal permeability of 8.78 ± 0.14 cm/h during the ex vivo permeation study. The acquired findings clearly revealed that the brinzolamide-loaded ultradeformable bilosomes show promising output and are useful in glaucoma therapy.
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Inhibidores de Anhidrasa Carbónica , Glaucoma , Animales , Femenino , Inhibidores de Anhidrasa Carbónica/farmacología , Pollos , Córnea , Glaucoma/tratamiento farmacológico , Tamaño de la PartículaRESUMEN
PURPOSE: To evaluate the concentrations of brimonidine and brinzolamide in the vitreous and aqueous humor after instillation of a 0.1% brimonidine tartrate and 1% brinzolamide fixed-combination ophthalmic suspension. METHODS: The present investigation involved patients with macular holes or idiopathic epiretinal membranes who were planning to undergo vitrectomy. One week prior to surgery, the patients received twice-daily topical treatment with 0.1% brimonidine tartrate and 1% brinzolamide fixed-combination ophthalmic suspension. Before vitrectomy, vitreous and aqueous humor samples were collected, and the mean concentrations of brimonidine and brinzolamide were determined through liquid chromatography-tandem spectrometry. RESULTS: Ten eyes (nine phakic and one pseudophakic eyes; 10 patients) were examined. The concentration of brimonidine in vitreous and aqueous humor samples was 5.02 ± 2.24 and 559 ± 670 nM, respectively. The concentration of brimonidine in the vitreous humor, which is needed to activate α2 receptors, was >2 nM in all patients. The concentration of brinzolamide was 8.96 ± 4.65 and 1100 ± 813 nM, respectively. However, there was no significant correlation between the concentrations of brimonidine in the vitreous and aqueous humor samples. CONCLUSIONS: Sufficient concentrations of brimonidine were detected in all vitreous samples. The dissociated correlation of the drug concentrations between aqueous and vitreous humors implies the possibility of another pathway to vitreous humor, different from the pathway to aqueous humor.
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Identifying critical attributes for complex locally acting ophthalmic formulations and establishing in vitro-in vivo correlations can facilitate selection of appropriate thresholds for formulation changes that reflect lack of impact on in vivo performance. In this study the marketed antiglaucoma product Azopt® (1% brinzolamide suspension) and five other brinzolamide formulations varying in particle size distributions and apparent viscosities were topically administered in rabbits, and their ocular pharmacokinetics was determined in multiple ocular tissues. Statistical evaluation with ANOVA showed no significant differences between the formulations in the peak drug concentration (Cmax) in the aqueous humor and iris-ciliary body. As a post-hoc analysis, the within animal and total variability was determined for Cmax in the aqueous humor and iris-ciliary body. Based on the observed variability, we investigated the sample size needed for two types of study designs to observe statistically significant differences in Cmax. For the sample size calculations, assuming both 25% and 50% true differences in Cmax between two formulations, two study designs were compared: paired-eye dosing design (one formulation in one eye and another formulation in the other eye of the same animal at the same time) versus parallel-group design. The number of rabbits needed in the paired-eye dosing design are much lower than in the parallel-group design. For example, when the true difference in aqueous humor Cmax is 25%, nine rabbits are required in the paired-eye design versus seventy rabbits (35 per treatment) in the parallel-group design to observe a statistically significant difference with a power of 80%. Therefore, the proposed paired-eye dosing design is a viable option for the design of pharmacokinetic studies comparing ophthalmic products to determine the impact of formulation differences.
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Ojo , Sulfonamidas , Animales , Conejos , Suspensiones , Tamaño de la Muestra , Humor Acuoso , Soluciones OftálmicasRESUMEN
Purpose: To investigate the ocular pharmacokinetic properties of intravitreally injected aflibercept in rabbits after using brinzolamide 1%/timolol maleate 0.5% fixed-combination eye drops. Methods: The right eye of 5 rabbits was topically administered 30 µL of brinzolamide and timolol maleate eye drops twice a day (q12h). The 2 eyes of each rabbit were injected with 1.0 mg (0.025 cc) of aflibercept on the 2nd day after instilling the eye drops. The intraocular pressure of the rabbits was measured before injection and sampling. The aqueous humor was drawn at 1, 3, 7, 14, 21, and 28 days. Aflibercept concentrations in aqueous humor and vitreous humor (28 days) were measured by enzyme-linked immunosorbent assay. Results: The aflibercept aqueous concentrations in the right eye at days 7, 14, 21, and 28 after injection were all significantly higher than those in the left eye (P > 0.05, n = 5). The peak aqueous concentrations of aflibercept in right eyes (49.5 µg/mL) and left eyes (50.9 µg/mL) were both observed at 1 day after injection. The elimination half-life of aflibercept in the aqueous humor of the right eye (4.70 days) was 1 day longer than that of the left eye (3.65 days). The average percentage of residual aflibercept in the vitreous humor of the right eye (3.35%) was also significantly higher than that of the left eye (0.63%). Conclusions: Brinzolamide 1%/timolol maleate 0.5% fixed-combination eye drops can significantly extend the ocular residence time of intravitreally injected aflibercept.
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Presión Intraocular , Timolol , Animales , Conejos , Soluciones Oftálmicas , Cuerpo Vítreo , Humor AcuosoRESUMEN
PURPOSE: To report the unforeseen complication of total obstruction of a glaucoma drainage implant (GDI) tube lumen by white deposit material and to present a preliminary report identifying the composition of this material. METHODS: Two subjects with a high IOP due to total obstruction of a GDI tube were reviewed. Both patients had a long history with brinzolamide and timolol maleate eye drops. The GDI tube was swept with a 5-0 polypropylene suture stent in order to open the tube. The intraluminal solid sample was successfully collected from the implant tube in one patient. High-performance liquid chromatography-mass spectrometry (HPLC-MS) was used to determine the origin of the intraluminal sample. RESULTS: Intraluminal deposits containing components of antiglaucoma drugs e.g., timolol and brinzolamide are a rare cause of total obstruction of GDI tubes. CONCLUSIONS: Our study describes a new cause of total obstruction GDI tubes. The long-term use of timolol maleate and brinzolamide and their presence in the intraluminal solid sample collected from the blocked GDI tube suggest that the glaucoma medication may have a role in the pathogenesis. However, the exact mechanism is unknown and requires further studies.
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Implantes de Drenaje de Glaucoma , Glaucoma , Humanos , Timolol/uso terapéutico , Presión Intraocular , Glaucoma/etiología , Glaucoma/cirugía , Glaucoma/tratamiento farmacológico , Implantes de Drenaje de Glaucoma/efectos adversosRESUMEN
PURPOSE: To evaluate the efficacy and safety of a new fixed combination of brinzolamide and timolol in patients with stages I and II of primary open-angle glaucoma (POAG). MATERIAL AND METHODS: Study patients were divided into 2 groups. The patients of the first group were prescribed Brinzolol Duo, the second group received an original drug Azarga. Regimen for both drugs was 1 drop 2 times per day for 84 days. The study included 7 monitoring visits: visit 0 (screening - 124 patients), visit 1 (randomization and treatment initiation - 120 patients), visits 2-4 (therapy), visit 5 (end of therapy - 117 patients), visit 6 (follow-up, study completion). RESULTS: Out of 120 patients included in the study, 117 subjects had completed all study procedures. It was shown that both compared drugs significantly reduce intraocular pressure (IOP). After 3 months, 46.5% of patients in the Brinzolol Duo group and 46.9% of patients in the Azarga group had IOP lowered by more than 30% compared to baseline, with IOP amounting to ≤18 mm Hg in 36.6% and 30.2% of patients, respectively. Hypotensive efficacy and safety of the drugs were comparable between the groups (p>0.05). The drugs were well tolerated, all adverse events (AEs) were mild or moderate in severity. CONCLUSION: The new drug Brinzolol Duo (brinzolamide + timolol) significantly reduces IOP in POAG patients with efficacy comparable to Azarga.
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Glaucoma de Ángulo Abierto , Hipertensión Ocular , Humanos , Timolol/efectos adversos , Glaucoma de Ángulo Abierto/diagnóstico , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Glaucoma de Ángulo Abierto/inducido químicamente , Hipertensión Ocular/tratamiento farmacológico , Presión Intraocular , Combinación de Medicamentos , Quimioterapia Combinada , Antihipertensivos/uso terapéutico , Resultado del TratamientoRESUMEN
We evaluated switching from brinzolamide 1% or brimonidine 0.1% to a fixed-combination of brinzolamide 1% and brimonidine 0.1%, and then determined the efficacy, safety, and satisfaction associated with these changes in glaucoma patients. This prospective, nonrandomized study evaluated a total of 31 enrolled glaucoma patients who underwent treatment with at least brinzolamide 1% or brimonidine 0.1%. Patients were administered a brinzolamide/brimonidine fixed-combination ophthalmic suspension (BBFC) after being switched from their original brinzolamide 1% or brimonidine 0.1% therapy. All other intraocular pressure (IOP)-lowering medications currently being used were continued. IOP, superficial punctate keratopathy (SPK), and conjunctival hyperemia data obtained at baseline and then at 4 and 12 weeks were evaluated. To assess the changes in treatment satisfaction, this study utilized the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). There was a significant decrease in the mean baseline IOP from 15.7 ± 4.9 mmHg to 13.6 ± 4.4 (p = 0.001) and 13.5 ± 3.9 mmHg (p = 0.002) at 4 and 12 weeks, respectively. Evaluation of the incidence of conjunctival hyperemia or SPK score showed there were no significant changes noted at any time point. The TSQM-9 score demonstrated there was a significant increase for effectiveness after switching from brinzolamide 1% or brimonidine 0.1% to BBFC. After switching from brinzolamide 1% or brimonidine 0.1% to BBFC, there was a significant decrease in the IOP. Patients were aware of the effectiveness of switching from brinzolamide 1% or brimonidine 0.1% to BBFC.
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Carbonic anhydrase inhibitors (CAIs) are prescription drugs also used in doping to dilute urine samples and tamper with urinalyses. Dorzolamide, brinzolamide, and acetazolamide are prohibited by the World Anti-Doping Agency. Detecting CAIs and their metabolites in biological samples is crucial to documenting misuse in doping. We quantified dorzolamide, brinzolamide, acetazolamide, and their metabolites in the urine and hair of 88 patients under treatment for ocular hypertension or glaucoma. Samples of the patients' relatives were analyzed to assess potential for accidental exposure. After washing, 25 mg hair was incubated with an acidic buffer at 100 °C for 1 h. After cooling and centrifugation, the supernatant was analyzed by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Urine (100 µL) was diluted and centrifuged before UHPLC-MS/MS analysis. Run time was 8 min through a reverse-phase column with a mobile phase gradient. MS/MS analysis was performed in a multiple-reaction monitoring mode after positive electrospray ionization. Median urinary concentration was 245 ng/mL (IQR: 116.2-501 ng/mL) for dorzolamide, 81.1 ng/mL (IQR: 35.9-125.3 ng/mL) for N-deethyl-dorzolamide, 0.77 ng/mL (IQR: 0.64 ng/mL-0.84 ng/mL) for N-acetyl-dorzolamide, 38.9 ng/mL (IQR: 20.4-79.2 ng/mL) for brinzolamide, and 72.8 ng/mL (IQR: 20.7-437.3 ng/mL) for acetazolamide. Median hair concentration was 0.48 ng/mg (IQR: 0.1-0.98 ng/mg) for dorzolamide, 0.07 ng/mg (IQR: 0.06-0.08 ng/mg) for N-deethyl-dorzolamide, 0.40 ng/mL (IQR: 0.13-1.95 ng/mL) for brinzolamide. Acetazolamide was detected in only one hair sample. Dorzolamide and brinzolamide were detected in the urine of three and one relatives, respectively. Cutoff concentrations of urinary dorzolamide and brinzolamide are necessary to preclude false positives due to contamination or passive exposure. We reported the first concentrations of brinzolamide in hair.
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Objectives: To investigate the intraocular pressure (IOP)-lowering efficacy, safety, and treatment tolerability of brinzolamide/brimonidine fixed combination (BBFC) in maximum medical therapy. Materials and Methods: The medical records of 92 patients with glaucoma or ocular hypertension who had previously been treated with a different antiglaucomatous regimen and were switched to a treatment regimen that included BBFC were retrospectively analyzed. Patients were divided into 4 groups including 22, 20, 27, and 23 patients based on previous glaucoma treatment. All patients received maximum medical treatment regimen by adding a combination of beta blocker-prostaglandin analogue therapy along with BBFC. IOP values at baseline and month 1, month 3 and month 6 after starting BBFC and ocular adverse effects at follow-up visits were evaluated. Results: The mean age of all patients was 62.7±16.6 years (range: 18-90). Fifty-two patients (56.5%) were women and 40 (43.5%) were men. Forty-eight (52.2%) patients had primary open-angle glaucoma, 35 (38.0%) had pseudoexfoliation glaucoma, and 9 (9.8%) had ocular hypertension. The IOP of the all eyes was 21.1±4.8 mmHg (range: 17-25) before and 17.6±3.7 mmHg, 17.3±3.4, and 17.0±3.5 mmHg at month 1, 3, and 6 after the introduction of BBFC, respectively (p<0.001 for all time points compared to baseline). In all 4 groups, a significant decrease in IOP was observed at month 1, 3, and 6 follow-ups compared to baseline after the introduction of BBFC. The mean number of antiglaucoma drops was significantly reduced from 2.5±0.6 at baseline to 2 after BBFC (p<0.001). The most frequent ocular adverse event was ocular allergic reactions reported in 8 patients (8.7%), conjunctival hyperemia in 5 patients (5.4%), and ocular discomfort in 2 patients (2.5%). Conclusion: Maximum medical therapy with BBFC provides significant IOP reduction and antiglaucoma therapy simplification with a favorable safety profile in patients with glaucoma.
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Glaucoma de Ángulo Abierto , Glaucoma , Hipertensión Ocular , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antihipertensivos/uso terapéutico , Tartrato de Brimonidina/efectos adversos , Tartrato de Brimonidina/uso terapéutico , Combinación de Medicamentos , Femenino , Glaucoma/tratamiento farmacológico , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Hipertensión Ocular/inducido químicamente , Hipertensión Ocular/tratamiento farmacológico , Estudios Retrospectivos , Sulfonamidas , Tiazinas , Adulto JovenRESUMEN
Aim and Objective: To compare the efficacy and safety of brinzolamide1% and timolol0.5% fixed combination eye drops versus dorzolamide2% and timolol0.5% fixed combination eye drops in the treatment of primary open-angle glaucoma. Design: Prospective, randomized, comparative, interventional study. Setting: Tertiary eye care centre. Material and Method: The present study was a comparative study carried out on patients visiting OPD of Ophthalmology Department and diagnosed with primary open-angle glaucoma. Group 1 (n-30 BT) received brinzolamide1% and timolol0.5% fixed combination eye drops, and Group 2 (N-30 DT) patients received dorzolamide2% and timolol0.5% fixed combination eye drops. A complete ophthalmic examination was performed, including Goldmann applanation tonometry. IOP was measured twice daily (9 AM and 4 PM). The patients were evaluated at 2, 4, 8, and 12 weeks. IOP was measured at follow-up. Side effects and tolerability of both drugs were assessed, and patient preference for drugs was noted. Results: Mean reduction in morning IOP was significantly more in Group 1 than in Group 2 at 8 weeks and 12 weeks (p < 0.05). Mean reduction in evening IOP was significantly more in Group 1 than in Group 2 at all follow-ups (p < 0.05). Conclusion: Brinzolamide1% + timolol0.5% fixed drug combination is more preferred and effective in lowering IOP than dorzolamide2% + timolol0.5% fixed drug combination in patients of primary open-angle glaucoma.
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PURPOSE: To investigate the effects of switching to brimonidine/brinzolamide fixed combination (BBFC) eye drops on intraocular pressure (IOP) and safety. STUDY DESIGN: A retrospective observational study. METHODS: We enrolled 238 patients with primary open-angle glaucoma or ocular hypertension who were switched to BBFC eye drops, from June 2020 to March 2021 from their previous medications without a washout period. Patients were divided into 3 groups based on previous medications: Group A, brimonidine and brinzolamide concomitantly; Group B, brinzolamide; and Group C, brimonidine. IOP at baseline, after 3 months, and after 6 months in each group were compared. RESULTS: In Group A (n = 102), there was no difference in IOP at baseline (14.4 ± 3.0 mmHg), 3 months (14.1 ± 3.1 mmHg), and 6 months (13.9 ± 2.8 mmHg). In Group B (n = 104), IOP significantly decreased at 3 months and 6 months (baseline, 14.8 ± 3.0 mmHg; 3 months, 13.1±2.6 mmHg; 6 months 13.8±2.9 mmHg; P < 0.0001). In Group C (n = 32), IOP significantly decreased at 3 months and 6 months (baseline, 16.2 ± 3.5 mmHg; 3 months, 15.2 ± 3.5 mmHg; 6 months, 14.6 ± 3.2 mmHg; P < 0.01). Adverse reactions occurred in 6.9%, 18.3%, and 15.6% in Groups A, B, and C, respectively. The frequent adverse reactions in all patients were conjunctival hyperemia (3.4%), conjunctivitis (2.9%), blepharitis (2.9%), and itching (2.5%). CONCLUSION: BBFC had satisfactory IOP-lowering effects without serious adverse reactions in patients who switched medications.
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Glaucoma de Ángulo Abierto , Hipertensión Ocular , Antihipertensivos/uso terapéutico , Tartrato de Brimonidina , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Humanos , Presión Intraocular , Hipertensión Ocular/tratamiento farmacológico , Soluciones Oftálmicas , Quinoxalinas/efectos adversos , Sulfonamidas , TiazinasRESUMEN
Aim: In this study, brinzolamide (BRZ) was loaded in balafilcon A silicone hydrogel soft contact lens to enhance delivery in glaucoma therapy. Materials & methods: BRZ-loaded soft contact lens was prepared by the soaking method with optimization of pH, temperature and concentration of drug loading solution. Results: At pH 7.4, loading temperature and concentration of 32°C and 3 mg/ml, respectively, enhanced drug loading capacity and release were observed. Diffusional experiments showed Higuchi model of release. BRZ loading brought no appreciable changes in the physical properties of soft contact lens, likewise, maintaining stability. Conclusion: The results demonstrated BRZ loading and delivery through silicone hydrogel soft contact lens which provides a potential alternative in glaucoma therapy.
Aim: In this study, brinzolamide (BRZ) was loaded in soft contact lens to improve drug delivery in glaucoma therapy. Materials & methods BRZ-loaded soft contact lens was prepared by the soaking method modifying pH, temperature and concentration of drug loading solution. Results: At pH 7.4, loading temperature and concentration of 32°C and 3 mg/ml, respectively, enhanced drug loading and release were observed. Diffusion is the main mechanism regulating drug release. BRZ loading brought no changes in the physical properties of soft contact lens, likewise, maintaining stability. Conclusion: The results demonstrated BRZ loading and delivery through soft contact lens which provides a potential alternative in glaucoma therapy.