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Cellular Physiology and Biochemistry :... 2015Besides its anti-allergic properties as a histamine receptor antagonist, olopatadine stabilizes mast cells by inhibiting the release of chemokines. Since olopatadine...
BACKGROUND/AIMS
Besides its anti-allergic properties as a histamine receptor antagonist, olopatadine stabilizes mast cells by inhibiting the release of chemokines. Since olopatadine bears amphiphilic features and is preferentially partitioned into the lipid bilayers of the plasma membrane, it would induce some morphological changes in mast cells and thus affect the process of exocytosis.
METHODS
Employing the standard patch-clamp whole-cell recording technique, we examined the effects of olopatadine and other anti-allergic drugs on the membrane capacitance (Cm) in rat peritoneal mast cells during exocytosis. Using confocal imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined their effects on the deformation of the plasma membrane.
RESULTS
Low concentrations of olopatadine (1 or 10 µM) did not significantly affect the GTP-γ-S-induced increase in the Cm. However, 100 µM and 1 mM olopatadine almost totally suppressed the increase in the Cm. Additionally, these doses completely washed out the trapping of the dye on the cell surface, indicating that olopatadine counteracted the membrane surface deformation induced by exocytosis. As shown by electron microscopy, olopatadine generated inward membrane bending in mast cells.
CONCLUSION
This study provides electrophysiological evidence for the first time that olopatadine dose-dependently inhibits the process of exocytosis in rat peritoneal mast cells. Such mast cell stabilizing properties of olopatadine may be attributed to its counteracting effects on the plasma membrane deformation in degranulating mast cells.
Topics: Animals; Anti-Allergic Agents; Cell Degranulation; Cell Membrane; Cells, Cultured; Dibenzoxepins; Exocytosis; Fluorescent Dyes; Male; Mast Cells; Membrane Potentials; Microscopy, Confocal; Microscopy, Electron; Olopatadine Hydrochloride; Patch-Clamp Techniques; Peritoneum; Rats; Rats, Wistar
PubMed: 25591779
DOI: 10.1159/000369704 -
Advances in Therapy Oct 2014The objective of this study was to compare the efficacy and safety of olopatadine versus epinastine in healthy Japanese adults with a history of allergic conjunctivitis... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The objective of this study was to compare the efficacy and safety of olopatadine versus epinastine in healthy Japanese adults with a history of allergic conjunctivitis to Japanese cedar pollen.
METHODS
This Phase IV double-blind randomized controlled clinical trial comprised three clinical visits over 30 days. Screening tests were performed to identify subjects with a history of allergic conjunctivitis to Japanese cedar pollen in terms of skin sensitivity and positive bilateral reactions to a conjunctival allergen challenge (CAC) with Japanese cedar pollen at Visit 1, and confirmation by a positive bilateral CAC reaction at Visit 2. At Visit 3, the subjects were randomized to receive one drop of olopatadine HCl ophthalmic solution 0.1% (olopatadine) in the left or right eye (1:1 ratio). All subjects received one drop of epinastine HCl ophthalmic solution 0.05% (epinastine) in the contralateral eye as an active control. Five min later, the subjects underwent bilateral CAC tests with one drop of the allergen solution at the concentration that elicited positive reactions at Visits 1 and 2. Efficacy outcomes included the severity of ocular itching at 5, 7, and 15 min and the severity of conjunctival hyperemia at 7, 15, and 20 min after the CAC test, as graded by the investigator by biomicroscopy.
RESULTS
Fifty people participated in this study (25 per group). Olopatadine significantly reduced ocular itching at 7 and 15 min (both p<0.05) and conjunctival hyperemia at 7 and 20 min (p=0.0010 and p<0.05, respectively) after allergen exposure compared with epinastine. There were no adverse events for either treatment.
CONCLUSION
The results of this single-dose study suggest that olopatadine is superior to epinastine in terms of suppressing ocular itching and hyperemia induced by Japanese cedar pollen during CAC tests. Further studies are needed to confirm these findings in real-life settings.
Topics: Adult; Allergens; Anti-Allergic Agents; Conjunctivitis, Allergic; Cryptomeria; Dibenzazepines; Double-Blind Method; Female; Humans; Imidazoles; Japan; Male; Olopatadine Hydrochloride; Ophthalmic Solutions; Pollen; Severity of Illness Index; Skin Tests; Treatment Outcome
PubMed: 25269854
DOI: 10.1007/s12325-014-0156-2 -
Advances in Therapy Oct 2014The efficacy and safety of the once-daily topical ophthalmic solutions, alcaftadine 0.25% and olopatadine 0.2%, in preventing ocular itching associated with allergic... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The efficacy and safety of the once-daily topical ophthalmic solutions, alcaftadine 0.25% and olopatadine 0.2%, in preventing ocular itching associated with allergic conjunctivitis were evaluated.
METHODS
Pooled analysis was conducted of two double-masked, multicenter, active- and placebo-controlled studies using the conjunctival allergen challenge (CAC) model of allergic conjunctivitis. Subjects were randomized 1:1:1 to receive alcaftadine 0.25%, olopatadine 0.2%, or placebo. The primary efficacy measure was subject-evaluated mean ocular itching at 3 min post-CAC and 16 h after treatment instillation. Secondary measures included ocular itching at 5 and 7 min post-CAC. Ocular itch was determined over all time points measured (3, 5, and 7 min) post-CAC and the proportion of subjects with minimal itch (itch score<1) and zero itch (itch score=0) was also assessed.
RESULTS
A total of 284 subjects were enrolled in the two studies. At 3 min post-CAC and 16 h after treatment instillation, alcaftadine 0.25% achieved a significantly lower mean itch score compared with olopatadine 0.2% (0.50 vs. 0.87, respectively; P=0.0006). Alcaftadine demonstrated a significantly lower mean itch score over all time points compared with olopatadine (0.68 vs. 0.92, respectively; P=0.0390); both alcaftadine- and olopatadine-treated subjects achieved significantly lower overall mean ocular itching scores compared with placebo (2.10; P<0.0001 for both actives). Minimal itch over all time points was reported by 76.1% of alcaftadine-treated subjects compared with 58.1% of olopatadine-treated subjects (P=0.0121). Treatment with alcaftadine 0.25% and olopatadine 0.2% was safe and well tolerated; no serious adverse events were reported.
CONCLUSION
Once-daily alcaftadine 0.25% ophthalmic solution demonstrated greater efficacy in prevention of ocular itching compared with olopatadine 0.2% at 3 min post-CAC (primary endpoint), and over all time points, 16 h post-treatment instillation. Alcaftadine and olopatadine both provided effective relief compared with placebo and were generally well tolerated.
Topics: Adult; Allergens; Anti-Allergic Agents; Benzazepines; Conjunctivitis, Allergic; Double-Blind Method; Drug Monitoring; Female; Humans; Imidazoles; Male; Middle Aged; Olopatadine Hydrochloride; Ophthalmic Solutions; Patient Outcome Assessment; Pruritus
PubMed: 25260889
DOI: 10.1007/s12325-014-0155-3 -
In vitro effects of preserved and unpreserved anti-allergic drugs on human corneal epithelial cells.Journal of Ocular Pharmacology and... Nov 2014Treatment with topical eye drops for long-standing ocular diseases like allergy can induce detrimental side effects. The purpose of this study was to investigate in... (Comparative Study)
Comparative Study
PURPOSE
Treatment with topical eye drops for long-standing ocular diseases like allergy can induce detrimental side effects. The purpose of this study was to investigate in vitro cytotoxicity of commercially preserved and unpreserved anti-allergic eye drops on the viability and barrier function of monolayer and stratified human corneal-limbal epithelial cells.
METHODS
Cells were treated with unpreserved ketotifen solution, benzalkonium chloride (BAC)-containing anti-allergic drugs (ketotifen, olopatadine, levocabastine) as well as BAC alone. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to determine cell viability. Effects of compounds on barrier function were analyzed measuring transepithelial electrical resistance (TEER) to determine paracellular permeability and rose bengal assays to evaluate transcellular barrier formation.
RESULTS
The BAC-preserved anti-allergic formulations and BAC alone significantly reduced cell viability, monolayer cultures being more sensitive to damage by these solutions. Unpreserved ketotifen induced the least diminution in cell viability. The extent of decrease of cell viability was clearly dependent of BAC presence, but it was also affected by the different types of drugs when the concentration of BAC was low and the short time of exposure. Treatment with BAC-containing anti-allergic drugs and BAC alone resulted in increased paracellular permeability and loss of transcellular barrier function as indicated by TEER measurement and rose bengal assays.
CONCLUSIONS
The presence of the preservative BAC in anti-allergic eye drop formulations contributes importantly to the cytotoxic effects induced by these compounds. Stratified cell cultures seem to be a more relevant model for toxicity evaluation induced on the ocular surface epithelia than monolayer cultures.
Topics: Anti-Allergic Agents; Benzalkonium Compounds; Cell Survival; Cells, Cultured; Dibenzoxepins; Electric Impedance; Epithelial Cells; Epithelium, Corneal; Humans; In Vitro Techniques; Ketotifen; Olopatadine Hydrochloride; Ophthalmic Solutions; Piperidines; Preservatives, Pharmaceutical
PubMed: 25100331
DOI: 10.1089/jop.2014.0030 -
Indian Journal of Pharmacology 2014Metronidazole alone rarely causes Stevens-Johnson syndrome (SJS). We present a case of an elderly male patient who, following metronidazole use, developed neurological...
Metronidazole alone rarely causes Stevens-Johnson syndrome (SJS). We present a case of an elderly male patient who, following metronidazole use, developed neurological symptoms followed by pain and blisters on both soles, erythema of face and neck, scrotal itching and erosion, and hemorrhagic encrustation around the lips and oral mucous membrane. Initial neurological symptoms followed by mucocutaneous manifestation of SJS following metronidazole use is probably a new presentation of this case.
Topics: Dental Health Services; Dibenzoxepins; Drug Therapy, Combination; Erythromycin; Famotidine; Humans; Lichen Planus, Oral; Male; Methylprednisolone; Metronidazole; Middle Aged; Olopatadine Hydrochloride; Stevens-Johnson Syndrome; Triamcinolone
PubMed: 24550598
DOI: 10.4103/0253-7613.125193 -
Acta Dermato-venereologica Jan 2014
Topics: Animals; Anti-Allergic Agents; Dermatitis, Atopic; Dibenzoxepins; Disease Models, Animal; Immunosuppressive Agents; Interleukins; Mice; Olopatadine Hydrochloride; Pruritus; Tacrolimus
PubMed: 23817562
DOI: 10.2340/00015555-1648 -
The World Allergy Organization Journal Feb 2013To identify the incidence of allergic conjunctivitis in patients with allergic rhinitis.
AIMS
To identify the incidence of allergic conjunctivitis in patients with allergic rhinitis.
METHODS
One hundred and eighty seven consecutive patients with allergic rhinitis (AR) were directly questioned if they have allergic conjunctivitis (AC) and this was clarified using standard screening questions relating to red, itchy and watery eyes recorded through a total ocular symptom score (TOSS). Patients were also asked about further symptoms that may be attributable to AC: eyelid dermatitis, frequent blinking; eye sensitivity and frontal headache from squinting or. blinking. All patients were given a drop of olopatadine hydrochloride 0.1% in each eye to help identify "silent" disease. 20 healthy non-atopic controls were also treated with olopatadine drops and questioned on ocular symptoms.
RESULTS
Fifty five percent of patients with AR were identified as having AC by direct questioning and the use of the TOSS questionaire. A further 41% were identifiable by asking additional questions and performing therapeutic challenge with olopadatine.
CONCLUSIONS
AC is a frequent comorbid condition occurring in 95% of our patients with AR. Only 55% of patients were able to identify that they had AC based on standard screening questions. Additional specific questioning and a therapeutic challenge in suspected patients can help identify patients who may benefit from treatment of AC.
PubMed: 23663473
DOI: 10.1186/1939-4551-6-4 -
Histamine H1-receptor antagonistic drug olopatadine suppresses TSLP in atopic dermatitis model mice.Allergology International : Official... Mar 2013
Topics: Animals; Cytokines; Dermatitis, Atopic; Dibenzoxepins; Disease Models, Animal; Gene Expression; Histamine H1 Antagonists; Mice; Olopatadine Hydrochloride; Thymic Stromal Lymphopoietin
PubMed: 23172358
DOI: 10.2332/allergolint.12-LE-0466 -
Clinical Ophthalmology (Auckland, N.Z.) 2012The 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...
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.
PubMed: 23152650
DOI: 10.2147/OPTH.S35431 -
Clinical, Cosmetic and Investigational... 2012The long-term follow-up of chronic urticaria (CU) is important to ensure the adequate treatment of patients. Olopatadine hydrochloride is one of the second-generation...
BACKGROUND
The long-term follow-up of chronic urticaria (CU) is important to ensure the adequate treatment of patients. Olopatadine hydrochloride is one of the second-generation nonsedating antihistamines.
METHODS
This study was designed to assess the optimal dose of olopatadine to suppress symptoms of chronic urticarial itch in well-controlled patients. After CU patients were treated with 10 mg olopatadine, patients having a visual analog scale (VAS) itch score of less than 20 were randomly allocated into one of three groups: 10 mg/day (n = 35), 5 mg/day (n = 30), or no medication (n = 32).
RESULTS
The suppressive effects of both the 5 mg and 10 mg olopatadine treatments on the VAS itch score were more significant and longer lasting over a period of 4 weeks than the no-medication treatment. Both the 5-mg group and the 10-mg group showed improved urticarial symptoms and maintained their VAS itch score within normal limits compared to the no-medication group. The differences between the 5-mg and 10-mg groups were not significant.
CONCLUSION
These results demonstrate that treatment with olopatadine at a dose of 5 mg once daily is effective and safe for the management and prevention of CU symptoms for itch in well-controlled patients.
PubMed: 23055763
DOI: 10.2147/CCID.S36812