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Background: Allergic conjunctivitis is increasing with the rise in the levels of allergens. Drug therapy is usually needed in addition to avoidance of general allergens to treat this condition. Both bepotastine besilate and olopatadine hydrochloride ophthalmic solutions are newer additions in the treatment of allergic conjunctivitis having dual properties of second-generation antihistaminics along with mast cell stabilizing activity. Aims and Objectives: The aim of the study was to compare the efficacy and tolerability of bepotastine besilate (1.5%) and olopatadine hydrochloride (0.1%) eye drops in patients presenting with allergic conjunctivitis in a tertiary care hospital of Southern part of India. Materials and Methods: Sixty patients who were clinically diagnosed to be suffering from allergic conjunctivitis were selected as participants for the study. They were randomly distributed into two groups consisting of 30 patients each. One group received eye drop bepotastine (1.5%) and the other group received eye drop olopatadine (0.1%), with each patient receiving the medication twice daily for a duration of 2 weeks. During the first visit, all the patients were assessed for the signs and symptoms and subsequently re-assessed at weekly intervals for a period of 2 weeks. They were also advised to report occurrence of any unwanted drug reaction during the weekly follow-up visits. Results: The above study showed the effectiveness of both bepotastine and olopatadine eye drops in decreasing the signs and symptoms of allergic conjunctivitis. Significant clinical improvement was found in all participants, whereas deterioration was found in none of them. Statistically significant improvement of itching and redness of eyes was observed with use of both the study drugs mentioned beforehand. Both the drugs were well tolerated by the patients. Statistically significant reduction of itching and foreign body sensation was found to be more in patients using bepotastine eye drops compared to those using olopatadine eye drops. Only two patients using bepotastine eye drops complained of having a mild burning sensation in eyes. Conclusion: From this study, bepotastine and olopatadine eye drops have been observed to be safe and efficacious in allergic conjunctivitis. Bepotastine eye drop was found to be more efficacious to relieve itching and foreign body sensation compared to that of olopatadine eye drops. [ABSTRACT FROM AUTHOR]

Background: Allergic conjunctivitis is increasing with the rise in the levels of allergens. Drug therapy is usually needed in addition to avoidance of general allergens to treat this condition. Both bepotastine besilate and olopatadine hydrochloride ophthalmic solutions are newer additions in the treatment of allergic conjunctivitis having dual properties of second-generation antihistaminics along with mast cell stabilizing activity. Aims and Objectives: The aim of the study was to compare the efficacy and tolerability of bepotastine besilate (1.5%) and olopatadine hydrochloride (0.1%) eye drops in patients presenting with allergic conjunctivitis in a tertiary care hospital of Southern part of India. Materials and Methods: Sixty patients who were clinically diagnosed to be suffering from allergic conjunctivitis were selected as participants for the study. They were randomly distributed into two groups consisting of 30 patients each. One group received eye drop bepotastine (1.5%) and the other group received eye drop olopatadine (0.1%), with each patient receiving the medication twice daily for a duration of 2 weeks. During the first visit, all the patients were assessed for the signs and symptoms and subsequently re-assessed at weekly intervals for a period of 2 weeks. They were also advised to report occurrence of any unwanted drug reaction during the weekly follow-up visits. Results: The above study showed the effectiveness of both bepotastine and olopatadine eye drops in decreasing the signs and symptoms of allergic conjunctivitis. Significant clinical improvement was found in all participants, whereas deterioration was found in none of them. Statistically significant improvement of itching and redness of eyes was observed with use of both the study drugs mentioned beforehand. Both the drugs were well tolerated by the patients. Statistically significant reduction of itching and foreign body sensation was found to be more in patients using bepotastine eye drops compared to those using olopatadine eye drops. Only two patients using bepotastine eye drops complained of having a mild burning sensation in eyes. Conclusion: From this study, bepotastine and olopatadine eye drops have been observed to be safe and efficacious in allergic conjunctivitis. Bepotastine eye drop was found to be more efficacious to relieve itching and foreign body sensation compared to that of olopatadine eye drops.

María Cecilia Marini,1 Martín Lucas Berra,2 Fernada Girado,3 Paula Alejandra Albera,4 Melina Sol del Papa,5 María Silvia Passerini,5 Alejandro Javier Aguilar6 1Ophthalmology Service, El Cruce-Nestor Kirchner High Complexity Hospital, Buenos Aires, Argentina; 2Cornea Transplant Service, Pedro Lagleyze Institute, Autonomous City of Buenos Aires, Argentina; 3Ophthalmology Service, Churruca-Visca Police Medical Complex, Autonomous City of Buenos Aires, Argentina; 4Ocular Surface Service, Santa Lucia Ophthalmological Hospital, Autonomous City of Buenos Aires, Argentina; 5Medical Affairs Department, Poen Laboratories, Autonomous City of Buenos Aires, Argentina; 6Ocular Surface Service, Lomas de San Isidro Medical Group, Buenos Aires, ArgentinaCorrespondence: Melina Sol del Papa, Medical Affairs Department, Poen Laboratories, Gómez de Fonseca 652, Autonomous City of Buenos Aires, C1407 ATL, Argentina, Tel +54 946 700100, Email investigacion@poen.net.arPurpose: To study the efficacy and toxic effects of bepotastine besilate 1.5% preservative-free (BB-PF) and olopatadine 0.2% BAK-preserved (OL-BAK) drops on the ocular surface of patients with allergic conjunctivitis.Patients and Methods: Ninety-seven patients with allergic conjunctivitis diagnosis participated in a prospective, multicenter, randomized, double-blind, controlled, parallel-group clinical trial. Patients received either BB-PF (n=48) or OL-BAK (n=49), both administered once daily in the morning. The patients were followed for 60 days. Ocular itching was the primary outcome measure. Secondary outcomes included ocular symptoms, signs, and non-ocular symptoms associated with rhinoconjunctivitis. Conjunctival impression cytology (CIC) was performed to evaluate histopathological changes related to the toxic effects of preservatives.Results: BB-PF treatment was associated with a 1.30 more probability of diminished ocular itching than OL-BAK (odds ratio (OR)=1.30; 95% CI=(0.96– 1.7); p=0.086). No statistically significant differences were found between treatments in the resolution of other ocular symptoms or signs, except for tearing, which was superior in the BB-PF (OR=1.37; 95% (1.26– 1.47); p< 0.0001). BB-PF was superior in terms of the resolution of rhinorrhea (p=0.040) and nasal itching (p=0.037). After 60 days of treatment, the BB-PF group exhibited 2.0 times higher probability of having a lower Nelson scale score compared to the OL-BAK group (OR=2.00; 95% CI=(1.19– 3.34); p=0.010).Conclusion: Both medications presented a similar efficacy in terms of the resolution of ocular signs and symptoms associated with ocular conjunctivitis. BB-PF is superior in the resolution of non-ocular symptoms and safer for the ocular surface than OL-BAK.Keywords: allergic conjunctivitis, bepotastine besilate, olopatadine, preservative-free, ocular surface, rhinoconjunctivitis

Purpose: To compare the efficacy and safety of Alcaftadine 0.25%, Olopatadine hydrochloride 0.2%, and Bepotastine besilate 1.5% ophthalmic solutions in the treatment of allergic conjunctivitis. Methods: This is a prospective, observer-masked, comparative study of 180 patients with mild to moderate allergic conjunctivitis, randomized into three groups of 60 patients each. Each group was assigned to be treated with one of the three treatment options namely Alcaftadine 0.25%, Olopatadine hydrochloride 0.2% and Bepotastine besilate 1.5% ophthalmic solutions. Patients were followed-up at regular intervals with relief and resolution of symptoms and signs noted using Total Ocular Scoring System (TOSS) and hyperaemia scale. Results: All three topical medications were effective in resolving symptoms of the patients with mild to moderate allergic conjunctivitis. Baseline mean TOSS scores for Alcaftadine group, Olopatadine group and Bepotastine besilate group were (7.68±2.32), (7.65±2.32) and (7.45±2.27) respectively as compared to the corresponding TOSS scores on 14th Day (4th visit) which were (0.2 ± 0.43), (0.4 ± 0.56) and (0.1 ± 0.36) respectively. The resolution of symptoms in the Bepotastine and Alcaftadine groups was significantly profound as compared to the Olopatadine group (p = 0.008). Bepotastine and Alcaftadine groups significantly reduced allergic conjunctivitis symptoms compared to Olopatadine group (p = 0.008). Conclusion: All three topical ophthalmic medications used in the study are safe and effective in the treatment of allergic conjunctivitis. However, Bepotastine and Alcaftadine appear to outweigh Olopatadine in resolving the symptoms of allergic conjunctivitis.

Purpose: To compare the efficacy and safety of Alcaftadine 0.25%, Olopatadine hydrochloride 0.2%, and Bepotastine besilate 1.5% ophthalmic solutions in the treatment of allergic conjunctivitis.Methods: This is a prospective, observer-masked, comparative study of 180 patients with mild to moderate allergic conjunctivitis, randomized into three groups of 60 patients each. Each group was assigned to be treated with one of the three treatment options namely Alcaftadine 0.25%, Olopatadine hydrochloride 0.2% and Bepotastine besilate 1.5% ophthalmic solutions. Patients were followed-up at regular intervals with relief and resolution of symptoms and signs noted using Total Ocular Scoring System (TOSS) and hyperaemia scale.Results: All three topical medications were effective in resolving symptoms of the patients with mild to moderate allergic conjunctivitis. Baseline mean TOSS scores for Alcaftadine group, Olopatadine group and Bepotastine besilate group were (7.68±2.32), (7.65±2.32) and (7.45±2.27) respectively as compared to the corresponding TOSS scores on 14th Day (4th visit) which were (0.2 ± 0.43), (0.4 ± 0.56) and (0.1 ± 0.36) respectively. The resolution of symptoms in the Bepotastine and Alcaftadine groups was significantly profound as compared to the Olopatadine group (p = 0.008). Bepotastine and Alcaftadine groups significantly reduced allergic conjunctivitis symptoms compared to Olopatadine group (p = 0.008).Conclusion: All three topical ophthalmic medications used in the study are safe and effective in the treatment of allergic conjunctivitis. However, Bepotastine and Alcaftadine appear to outweigh Olopatadine in resolving the symptoms of allergic conjunctivitis. [ABSTRACT FROM AUTHOR]

Bepotastine (BPT) is a H 1 -receptor antagonist. It is used as a besilate salt in ophthalmic solution for allergic conjunctivitis and orally for the treatment of allergic rhinitis and urticaria/pruritus. Its systematic forced degradation study is unreported. The same was carried out in different conditions prescribed by International Conference on Harmonisation. The stressed solutions were subjected to reversed phase liquid chromatographic analysis, and BPT was observed to be labile under photobasic condition only, yielding 5 photodegradation products. The structures of the latter were elucidated from data generated by liquid chromatography–high-resolution mass spectrometry and multistage mass spectrometry. Of the 5, 4 products were further isolated and subjected to nuclear magnetic resonance spectroscopy to justify the proposed structures. Two of them, with similar accurate mass, were additionally and unambiguously characterized from their heteronuclear multiple bond correlation data, hydrogen deuterium exchange mass data, and quantum chemical analysis using density functional theory calculations. One degradation product had a structure that could only be explained by unusual rearrangement involving conversions of N-oxide into hydroxylamine, similar to Meisenheimer rearrangement. The physicochemical, as well as absorption, distribution, metabolism, excretion, and toxicity properties of BPT and its characterized photodegradation products were evaluated in silico by ADMET Predictor™ software. [ABSTRACT FROM AUTHOR]

Background: Rituximab, an anti-CD20 monoclonal antibody, can cause infusion reactions (IRs), especially during the initial rituximab infusion therapy. Generally, patients are administered a histamine H 1 -receptor antagonist before the rituximab infusion, along with an antipyretic analgesic, to prevent or reduce IRs. Multiple retrospective case-control studies indicate that the second generation of histamine H 1 -receptor antagonists might be more effective than the first generation in suppressing IRs caused by the rituximab infusion., Objective: This study aimed to assess the efficacy of first- and second-generation histamine H 1 -receptor antagonists for preventing IRs resulting from the initial infusion of rituximab in patients diagnosed with non-Hodgkin lymphoma., Methods: This is a phase II, double-blind, active-controlled randomized trial. It will be a multicenter study conducted across 3 facilities that aims to enroll a total of 40 patients diagnosed with non-Hodgkin lymphoma who will receive their initial rituximab infusion. Participating patients will be administered hydroxyzine pamoate or bepotastine besilate, representing first- or second-generation histamine H 1 -receptor antagonists, respectively. This will be combined with 400-mg acetaminophen tablets taken approximately 30 minutes before the first infusion of rituximab. The primary end point of this trial is to assess severe IRs, equivalent to grade 2 or higher as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0, that occur within a 4-hour period after the initiation of rituximab infusion. The secondary end points include assessing the severity of the initial IR, the maximum severity of the IR, and the duration between rituximab infusion initiation and the onset of the first IR within a 4-hour period. Additionally, the trial will evaluate histamine H 1 -receptor antagonist-induced drowsiness using the visual analogue scale, with each patient providing their individual response., Results: This study began with patient recruitment in April 2023, with 17 participants enrolled as of November 12, 2023. The anticipated study completion is set for February 2026., Conclusions: This study is the first randomized controlled trial comparing the effects of oral first- and second-generation histamine H 1 -receptor antagonists in preventing IRs induced by the initial administration of rituximab. The findings from this study hold the potential to establish the rationale for a phase III study aimed at determining the standard premedication protocol for rituximab infusion., Trial Registration: Japan Registry of Clinical Trials jRCTs051220169; https://jrct.niph.go.jp/latest-detail/jRCTs051220169., International Registered Report Identifier (irrid): DERR1-10.2196/54882., (©Yumi Kitahiro, Kazuhiro Yamamoto, Kimikazu Yakushijin, Takeshi Ioroi, Masaaki Tanda, Kotaro Itohara, Tomohiro Omura, Hironobu Minami, Ikuko Yano. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 22.02.2024.)

Bepotastine Besilate is an anti-histaminic drug and it is marketed as tablet of strength 10mg. In this study an attempt is made to monitor the dissolution of Bepotastine Besilate tablet. Dissolution study was done for marketed sample using phosphate buffer 6.8, phosphate buffer 4.5 and 0.1 N HCl as dissolution media. Samples were analysed using UV spectrophotometer, HPLC and HPTLC. Detection wavelength selected was 226nm. A chromatographic separation is achieved on a C18 column with a mobile phase consisting of acetonitrile, water with isocratic elution with flow rate 1ml/min. Solvents used for development in HPTLC were chloroform and methanol. Percentage release of bepotastine besilate was calculated by extrapolation of calibration curve. The results of three analytical methods were compared by applying One-Way ANOVA. [ABSTRACT FROM AUTHOR]

Background: Bepotastine besilate ophthalmic solution (BBOS) 1.5% is a topical antihistamine for the treatment of ocular itching associated with allergic conjunctivitis (AC). Allergic rhinitis and AC are common comorbid conditions. We explored the efficacy of BBOS 1.5% in alleviating nasal symptoms in an integrated analysis of two Phase III conjunctival allergen challenge (CAC) studies and a Phase IV environmental allergen study. Methods: In the Phase III trials, a CAC was performed 15 minutes, 8 hours, and 16 hours following ocular instillation of BBOS 1.5% (n=78) or placebo (n=79), and subjects evaluated nasal symptoms. In the environmental study, subjects instilled BBOS 1.5% (n=123) or placebo (n=122) twice daily and nasal symptoms were evaluated over 2 weeks. Results: In the Phase III trials, BBOS 1.5% had reduced CAC-induced nasal congestion and pruritus at 15 minutes and 8 hours postdosing and rhinorrhea and a non-ocular compositesymptom score (sum of nasal scores plus ear or palate pruritus) at all time points postdosing (all P=0.01 vs placebo). In the Phase IV environmental study, BBOS 1.5% reduced sneezing and nasal pruritus over 2 weeks and median number of days to improvement of nasal pruritus and total nasal symptom score (sum for rhinorrhea, sneezing, nasal pruritus, and nasal congestion; P≤0.04 vs placebo). Additionally, investigator-reported improvement in overall ocular (pruritus, hyperemia, tearing) and nasal symptoms was greater with BBOS 1.5% vs placebo (P≤0.03). Conclusion: Results of these exploratory analyses indicate that topical ocular BBOS 1.5% reduced nasal symptoms, supporting its use for alleviating rhinitis symptoms associated with AC. [ABSTRACT FROM AUTHOR]

The objective of the present study was to develop sustained release gastro-retentive (SRGR) tablet formulation of bepotastine besilate for once-a-day dosing using quality by design (QbD) approach. Quality target product profile (QTPP) of bepotastine besilate SRGR tablet formulation was defined and critical quality attributes (CQAs) were identified. Potential risk factors were identified using fish bone diagram and failure mode effect analysis (FMEA) tool and screened by Plackett-Burman design and finally bepotastine besilate SRGR tablet formulation was optimized using Box-Behnken design. It was observed that formulation variables X1: hydrophobic release controlling agent (mg/tab) and X2: hydrophilic release controlling agent (mg/tab) have strikingly influenced drug release (%) (Y1), while floating lag time (min) (Y2) was significantly impacted by formulation variable X4: gas generating agent (mg/tab). A design space plot within which the CQAs remained unchanged was established at lab scale. In conclusion, this study demonstrated the suitability of a hydrophobic-hydrophilic polymer combination along with gas generating agent to achieve SRGR tablet formulation for once-a-day dosing of bepotastine besilate using systematic QbD approach. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of present study was to design and evaluate bepotastine besilate ophthalmic solution 1.5% to develop a stable formulation using buffering agent, tonicity modifier and preservative. Method: In this study the concentration of preservative and tonicity modifier concentration are adjusted in such a way so that the final formulation will have least concentration of preservative still it will be protected from microorganisms and isotonic so that after instillation when formulation will come in contact with tissues there should not be any swelling, contraction or discomfort. Result: The preservative content was selected in the range of 0.002-0.012% and tonicity modifier in the range of 0.45-0.9%. Bepotastine besilate ophthalmic solution 1.5% filled in LDPE container having fill volume 5 mL is clear, colourless solution having pH range 6.8-7.0, drop size of 38.6 µl and % water loss after 3 months as 1.9748%. The percent purity of bepotastine besilate and preservative was determined using RP-HPLC method was found to be 100.50 and 51.648% with % RSD as 0.84 and 0.65% respectively. The samples of the formulation also subjected to stability as per ICH guidelines and 6 months data was generated. Draize test protocol was also followed to study invivo eye irritancy of the formulation to produce a safe and effective formulation. Conclusion: Laboratory prepared formulation of bepotastine besilate ophthalmic solution 1.5% has showed good stability at both 25°C and 40°C as the drug and preservative content was within the accepted range. [ABSTRACT FROM AUTHOR]

Allergic conjunctivitis (AC) affects an estimated 20% of the population in the Western world, with a large fraction suffering due to seasonal or perennial allergen exposures. Bepotastine besilate ophthalmic solution (BBOS) 1.5%, a dual-acting histamine (H1) receptor antagonist and mast cell stabilizer, is indicated for itching associated with AC. This study was designed to evaluate the efficacy and safety of BBOS 1.5% for reducing ocular itching associated with AC in subjects enrolled in a natural exposure trial. Eligible subjects in a multicenter, double-masked, randomized, parallel-group, placebo-controlled, natural exposure clinical trial were randomly assigned to either BBOS 1.5% or placebo eyedrops on a 1:1 basis and instilled 1 drop of the test agent into both eyes twice daily for 2 weeks. The mean change from baseline in instantaneous and reflective ocular itching scores at the end of 2 weeks of treatment were evaluated based on subject-assessed severity of instantaneous and reflective itching. Subject-reported adverse events (AEs) were also recorded for safety. Treatment with BBOS 1.5% significantly reduced instantaneous and reflective ocular itching scores from baseline compared with placebo over the 2-week study period (p = 0.007 and p = 0.005, respectively). BBOS 1.5% was well tolerated, and AEs were generally transient and mild. This clinical study indicates BBOS 1.5% effectively and safely treated ocular itching in a natural exposure allergy study and is a useful treatment option for the management of ocular itching associated with AC. (ClinicalTrials.gov identifier number: NCT01174823.) [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to compare patient-perceived relief of ocular itch, nasal symptoms, and eye drop comfort when allergic conjunctivitis was treated with bepotastine besilate 1.5% versus olopatadine hydrochloride 0.2%. Methods: This randomized, observer-masked, single-center, crossover study included 30 patients with ocular itching associated with allergic conjunctivitis accompanied by nasal symptoms. Patients were treated with bepotastine besilate 1.5% twice daily (7 am and 4 pm) or olopatadine hydrochloride 0.2% once daily (7 am) for 14 days. Following a 7-day washout period during which only preservative-free artificial tears were used twice daily, patients were crossed over to the alternative treatment for 14 days. Parameters evaluated by twice-daily patient diaries included each treatment's ability to relieve ocular itch, ability to relieve itchy/runny nose, ability to relieve ocular allergy symptoms, and eye drop comfort. At the conclusion of the study, patients were also asked to identify which agent provided better all-day relief of ocular itching, better all-day relief of itchy/runny nose, superior comfort, and for which treatment they would prefer a prescription. Results: According to the mean daily diary responses, bepotastine besilate 1.5% provided significantly better relief of evening ocular itch, relief of morning and evening itchy/runny nose, and relief of morning and evening ocular allergy symptoms. At study end, 63.3% and 66.7% of patients preferred bepotastine besilate 1.5% for all-day relief of ocular itching and all-day relief of itchy/runny nose, respectively. At study end, there was no significant difference in the number of patients preferring one treatment over the other for comfort. Overall, 66.7% of patients stated that they would prefer to treat their allergic conjunctivitis with bepotastine besilate 1.5% over olopatadine hydrochloride 0.2%. Conclusion: Based on their evaluation of therapeutic performance, patients preferred bepotastine besilate 1.5% over olopatadine hydrochloride 0.2% by two-to-one for the treatment of allergic conjunctivitis. [ABSTRACT FROM AUTHOR]

The Skindex-16 questionnaire was recently developed as a measure of dermatological health-related quality of life (HRQoL), including symptoms, emotions and functional aspects. Bepotastine besilate is a selective histamine H1-receptor antagonist and a second-generation non-sedating antihistamine to treat various dermatological disorders. We assessed changes of the HRQoL instrument (Skindex-16) on patients with pruritus, including those with atopic dermatitis (AD) over bepotastine treatment period. The patients' personal assessment of the intensity of pruritus was determined using the Visual Analog Scale (VAS) for pruritus. Patients answered the Skindex-16 at baseline and at week 4. Forty-eight of 51 enrolled dermatological patients completed the Skindex-16. Of the 48 patients, 11 had AD and 37 had other conditions. Improvement in the clinical evaluation and VAS score was significant in all patients, the AD group and the other disorders group between baseline and week 4. Skindex-16 showed significantly lower scores for each of the three scales (symptoms, emotions and functioning) and the global score at baseline compared to that at week 4 in all patients and the other disorders. In contrast, there was a significant reduction in the emotions and global score among the AD patients. We found a significant correlation between falls in emotions score of Skindex-16 and falls in VAS scores for pruritus in the AD group. Bepotastine could be effective in the management of patients' HRQoL and useful in patients suffering with pruritus. We suggested that pruritus of AD patients could exert a stronger emotional effect due to the skin condition compared to the symptomatic or functional effects. [ABSTRACT FROM AUTHOR]

Background: Urticaria is mainly caused by mast cell-derived histamine through the histamine H1 receptor. Antihistamines are occasionally used on demand upon a recurrence of urticaria; therefore, rapidly acting agents should be explored. The onset of action is assumed to depend on time to maximum concentration (Tmax), but the speed of action needs to be evaluated not only through blood concentration analysis but also by measuring in vivo effectiveness. Methods: In this study, we chose two representative second-generation antihistamines (bepotastine and fexofenadine) with relatively short Tmax values and evaluated their effects on histamine-induced skin responses using both visual and laser Doppler imaging scales. Results: Suppression of histamine-induced flare and itch was observed 3 and 6 h after administration of both antihistamines. Attenuation of itch was seen 30 min after the administration of each drug and thereafter until 6 h. In addition, bepotastine suppressed flare formation after only 30 min following application. Conclusion: These results suggest that antihistamines suppress histamine-induced itch and flare, followed by wheal formation, and that bepotastine suppresses skin symptoms sooner after administration than fexofenadine does, which is relatively consistent with the Tmax results. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Allergic conjunctivitis is a clinical reaction to environmental allergens and is manifested by ocular itching caused by IgE-induced mast cell degranulation. Bepotastine besilate is a selective H1-antagonist with mast cell stabilizing properties. This report examines the reduction of ocular itching integrated from two conjunctival allergen challenge (CAC) clinical trials comparing bepotastine besilate ophthalmic solution (BBOS) 1.5% to placebo in subjects with a history of allergic conjunctivitis. Two phase III, double-masked, placebo-controlled, parallel-group, CAC clinical trials evaluated BBOS 1.5% versus placebo to reduce ocular itching. Eligible subjects were randomly assigned 1:1 to either BBOS 1.5% (n = 78) or placebo (n = 79). Ocular itching was graded by subjects using a standardized scale (0-4 U). Adverse events and ophthalmic clinical findings were recorded for safety. BBOS 1.5% was superior to placebo for reducing CAC-induced ocular itching (p < 0.0001) as early as 3 minutes post-CAC and for at least 8 hours after dosing. Post hoc analyses examining several populations also showed a significant improvement (p < 0.0001) for subjects with more severe itching response at screening and for the proportion of subjects with complete or nearly complete resolution of CAC-induced itching, both outcomes supporting the clinical benefit of BBOS 1.5%. Adverse events were generally transient and mild. BBOS 1.5% is safe and effective in the treatment of ocular itching associated with allergic conjunctivitis within 3 minutes of a CAC and with a sustained duration of action of at least 8 hours. (ClinicalTrials.gov numbers: NCT00424398 and NCT00586664). [ABSTRACT FROM AUTHOR]

Abstract: To elucidate the ocular pharmacological properties of bepotastine besilate, a selective histamine H1 receptor antagonist, when compared with other histamine H1 receptor antagonists, using guinea pig allergic conjunctivitis models and in vitro models of eosinophil recruitment and mast cell membrane stabilization. Conjunctival vascular hyperpermeability was studied in guinea pigs passively sensitized with anti-ovalbumin antiserum or following subconjunctival injection of histamine. Modulation of eosinophil recruitment was evaluated for both platelet-activating factor (PAF)-induced eosinophil infiltration in guinea pigs and leukotriene B4-induced in vitro chemotaxis of guinea pig peritoneal eosinophils. Membrane-stabilizing effects of bepotastine also were studied with rat peritoneal mast cells stimulated with the ionophore A23187. Histamine H1 receptor antagonists including bepotastine besilate were topically administered before ovalbumin, histamine or PAF challenges for in vivo experiments or were added directly to mast cell and eosinophil medium in vitro. Bepotastine besilate significantly inhibited conjunctival vascular hyperpermeability in a dose-dependent manner with maximal effect for bepotastine besilate 1.5%. In separate in vivo experiments, bepotastine besilate 1.0% was significantly more effective than levocabastine 0.025% in the passive sensitization model or olopatadine 0.1% in the histamine-induced hyperpermeability model. Bepotastine besilate 1.0% further suppressed PAF-induced eosinophil infiltration into conjunctival tissue more effectively than ketotifen 0.05%. Chemotaxis of guinea pig peritoneal eosinophils and histamine release from rat peritoneal mast cells in vitro were also inhibited by addition of bepotastine. Olopatadine had a weak effect as compared to that of bepotastine on eosinophil chemotaxis and no effect on mast cell histamine release in our study conditions. Bepotastine besilate was more potent than olopatadine, ketotifen, or levocabastine in reducing vascular hyperpermeability in various animal models of allergic conjunctivitis. Mast cell function and eosinophil chemotaxis were also inhibited in vitro with bepotastine, suggesting bepotastine acts as an inhibitor of allergic response through multiple mechanisms: histamine H1 receptor antagonism, mast cell stabilization, and inhibition of eosinophil migration to ocular inflammatory sites. [Copyright &y& Elsevier]

Abstract: Background: Bepotastine besilate is a highly selective histamine H1-receptor antagonist with antihistaminic, mast cell stabilizing, and anti-inflammatory activity. Based on a history of clinical effectiveness and tolerability of oral bepotastine besilate in the treatment of allergic symptoms, bepotastine besilate is being tested as a potential ophthalmic medication for allergic conjunctivitis. Objective: The aim of this study was to assess the effects of bepotastine besilate ophthalmic solution 1.0% and 1.5% for the treatment of ocular itching and conjunctival hyperemia in a conjunctival allergen challenge (CAC) model in adults and children. Methods: This Phase III, single-center, prospective, randomized, double-masked, placebo-controlled, CAC clinical trial enrolled patients ≥10 years of age with a history of allergic conjunctivitis, skin-test reaction, and CAC response. Patients received bepotastine besilate ophthalmic solution 1.0%, bepotastine besilate ophthalmic solution 1.5%, or placebo, 1 drop on each eye on days 14 ± 3 and 28 ± 3. The primary efficacy end points, patient-assessed ocular itching (at 3, 5, and 7 minutes) and investigator-assessed conjunctival hyperemia (at 7, 15, and 20 minutes), were determined after CAC according to standardized 5-point scales (0 = none to 4 = severe). Clinical significance was defined in the protocol as ≥1.0-U between-group difference in mean ocular itching scores at the majority of time points at a study visit and also a ≥0.5-U difference at all time points. Tolerability of the test agent was assessed by visual acuity, slit-lamp biomicroscopy, intraocular pressure, dilated funduscopy, and adverse events. Results: A total of 107 patients (male, 54%; age range, 11–73 years; white race/ethnicity, 93%) received investigational product and comprised the intent-to-treat (ITT) population (bepotastine besilate ophthalmic solution 1.0%, 36 patients; bepotastine besilate ophthalmic solution 1.5%, 35; and placebo, 36). All 107 patients received investigational product at visit 3A (day 0) and were included in the ITT population. Of the 107 patients who were enrolled, 103 completed the study without a protocol deviation or violation. The 1.0% and 1.5% solutions were associated with clinically and statistically significant reductions in mean ocular itching scores compared with placebo on the 15-minute onset-of-action and 8-hour duration-of-action CAC tests (reductions, 1.3–1.5 U and 1.0–1.7 U respectively; all, P < 0.001). Statistically significant reductions in conjunctival hyperemia were achieved with both bepotastine besilate concentrations. Overall, 13 patients experienced a treatmentemergent adverse event considered related to the study drug (bepotastine besilate ophthalmic solution 1.0%, 6 patients; bepotastine besilate ophthalmic solution 1.5%, 4; and placebo, 3). Conclusions: In this CAC model of allergic conjunctivitis in adults and children, bepotastine besilate ophthalmic solutions 1.0% and 1.5% were associated with clinically and statistically significant reductions in ocular itching, but not conjunctival hyperemia, within 15 minutes that were maintained for at least 8 hours after administration. Both solutions were well tolerated. ClinicalTrials.gov identifier: NCT00424398. [Copyright &y& Elsevier]

Background: Pruritus is the most severe problem in atopic dermatitis. Even though its mechanism is still not fully understood, antihistamines have been prescribed for atopic dermatitis. Objective: To evaluate the effect of antihistamine on atopic dermatitis, we analyzed the scratching behavior in atopic dermatitis model NC/Nga mice. Methods: BALB/c mice, in which scratching behavior was induced by intradermal injection of compound 48/80 (100 μg/100 μl/mouse), and NC/Nga mice, housed in a conventional environment and having developed spontaneous eczematous regions, were monitored with a SCLABA system after oral administration of bepotastine besilate. The number of eosinophils in the ear skin and the serum leukotriene B4 (LTB4) levels were also evaluated. Results: Bepotastine at doses of 3 and 10 mg/kg effectively inhibited the compound 48/80-induced scratching behavior of BALB/c mice 1 h after oral administration, comparable with the blood Tmax, which was reached within 0.8–1.6 h in humans. Bepotastine also significantly inhibited the scratching behavior of NC/Nga mice 1 h after oral administration. Even though 10 mg/kg bepotastine could not influence the number of tissue eosinophils, it effectively suppressed the serum LTB4 levels, just comparable with the suppression of scratch behavior of NC/Nga mice. Conclusion: Bepotastin effectively suppressed the scratch behavior of atopic dermatitis model mice, which may not simply be explained by the suppression of histamine but also by the suppression of other mediators like LTB4. Bepotastine could be useful in the treatment of pruritus, especially early after oral administration. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Anti-pruritic effects of the antihistamine bepotastine besilate were studied in mice. Bepotastine besilate (10 mg/kg) inhibited scratching induced by an intradermal injection of histamine (100 nmol/site), but not serotonin (100 nmol/site). Bepotastine besilate (1–10 mg/kg, oral) dose-dependently suppressed scratching induced by substance P (100 nmol/site) and leukotriene B4 (0.03 nmol/site). An intradermal injection of substance P (100 nmol/site) increased the cutaneous concentration of leukotriene B4, which was not affected by bepotastine besilate (10 mg/kg, oral). Leukotriene B4 increased Ca2+ concentration in cultured neutrophils, which was suppressed by bepotastine besilate (1–100 μM). Leukotriene B4 increased Ca2+ concentration in cultured dorsal root ganglion neurons, which was also suppressed by bepotastine besilate (100 μM). The results suggest that the inhibition of the actions of leukotriene B4 as well as histamine is involved in the anti-pruritic effect of bepotastine besilate. [Copyright &y& Elsevier]