Synchronous Fluorescence as a Green and Selective Method for the Simultaneous Determination of Cetirizine and Azelastine in Aqueous Humor.

A green, simple, quick and economical method is implemented for the first time for the simultaneous estimation of cetirizine (CTZ) and azelastine (AZE) as co-administered eye drops. The method relies on synchronous spectrofluorimetry with ∆λ = 60 nm. Cetirizine can be estimated at 231 nm and AZE can be measured at 294 nm, each at the other's zero crossing point. All factors affecting the method were studied and properly optimized. Good correlation was obtained in the range of 0.1-2 µg mL-1 for both drugs. The limits of detection were 0.014 and 0.010 µg mL-1 and limits of quantitation were 0.043 and 0.029 µg mL-1 for CTZ and AZE, respectively. Moreover, ICH guidelines were carried out to validate the adopted method. The method was suitable for the analysis of CTZ and AZE in synthetic mixtures, eye drops and aqueous humor. The mean percentage of recoveries of CTZ and AZE in spiked aqueous humor were 99.83 and 99.37, respectively. Furthermore, Green Analytical Procedure Index (GAPI) and analytical Eco-scale approaches were used to evaluate the greenness of the suggested method.

The Multidirectional Effect of Azelastine Hydrochloride on Cervical Cancer Cells.

A major cause of cancer cell resistance to chemotherapeutics is the blocking of apoptosis and induction of autophagy in the context of cell adaptation and survival. Therefore, new compounds are being sought, also among drugs that are commonly used in other therapies. Due to the involvement of histamine in the regulation of processes occurring during the development of many types of cancer, antihistamines are now receiving special attention. Our study concerned the identification of new mechanisms of action of azelastine hydrochloride, used in antiallergic treatment. The study was performed on HeLa cells treated with different concentrations of azelastine (15-90 µM). Cell cycle, level of autophagy (LC3 protein activity) and apoptosis (annexin V assay), activity of caspase 3/7, anti-apoptotic protein of Bcl-2 family, ROS concentration, measurement of mitochondrial membrane potential (Δψm), and level of phosphorylated H2A.X in response to DSB were evaluated by cytometric method. Cellular changes were also demonstrated at the level of transmission electron microscopy and optical and fluorescence microscopy. Lysosomal enzyme activities-cathepsin D and L and cell viability (MTT assay) were assessed spectrophotometrically. Results: Azelastine in concentrations of 15-25 µM induced degradation processes, vacuolization, increase in cathepsin D and L activity, and LC3 protein activation. By increasing ROS, it also caused DNA damage and blocked cells in the S phase of the cell cycle. At the concentrations of 45-90 µM, azelastine clearly promoted apoptosis by activation of caspase 3/7 and inactivation of Bcl-2 protein. Fragmentation of cell nucleus was confirmed by DAPI staining. Changes were also found in the endoplasmic reticulum and mitochondria, whose damage was confirmed by staining with rhodamine 123 and in the MTT test. Azelastine decreased the mitotic index and induced mitotic catastrophe. Studies demonstrated the multidirectional effects of azelastine on HeLa cells, including anti-proliferative, cytotoxic, autophagic, and apoptotic properties, which were the predominant mechanism of death. The revealed novel properties of azelastine may be practically used in anti-cancer therapy in the future.

[Effective intranasal GCS application strategy of mono and combines forms in treating patients, suffering from allergic rhinitis. Evidence-based medicine to help a practitioner]. / Effektivnaya strategiya primeneniya mono- i kombinirovannykh form intranazal'nykh glyukokortikosteroidov v lechenii patsienta s allergicheskim rinitom. Dokazatel'naya meditsina v pomoshch' prakticheskomu vrachu.

OBJECTIVE: To summarize effective intranasal glucocorticosteroids (GCS) application strategies in treatment of patients, suffering from allergic rhinitis (depending on disease type), based on actual research results. Current study determines the place of fixed intranasal GCS and topic antihistamine medication combination, specifically azelastine and mometasone furoate, as a first line of choice therapy in treatment of patients, suffering from allergic rhinitis. Effective application of stage therapy allows us establish control over allergic inflammation and significantly decrease pharmaceutical load in cases of patients, suffering from allergic rhinitis.

MP-AzeFlu in Moderate-to-Severe Allergic Rhinitis: A Literature Review.

Allergic rhinitis (AR) is prevalent, and many patients present with moderate-to-severe symptomatic disease. The majority of patients are not satisfied with their AR treatment, despite the use of concurrent medications. These gaps underscore the need for treatment with more effective options for moderate-to-severe AR. The authors' objective was to review systematically the efficacy and safety of MP-AzeFlu for the treatment of AR. The primary outcomes studied were nasal, ocular, and total symptoms. Other outcomes included time to onset and of AR control, quality of life, and safety. Searches of PubMed and Cochrane databases were conducted on May 14, 2020, with no date restrictions, to identify publications reporting data on MP-AzeFlu. Clinical studies of any phase were included. Studies were excluded if they were not in English, were review articles, did not discuss the safety and efficacy of MP-AzeFlu for AR symptoms. Treatment of AR with MP-AzeFlu results in effective, sustained relief of nasal and ocular symptoms, and faster onset and time to control compared with intranasal azelastine or fluticasone propionate. Long-term use of MP-AzeFlu was safe, with benefits in children, adults, and adults aged ≥65 years. Other treatment options, including fluticasone propionate and azelastine alone or the combination of intranasal corticosteroids and oral antihistamine, do not provide the same level of efficacy as MP-AzeFlu in terms of rapid and sustained relief of the entire AR symptom complex. Furthermore, MP-AzeFlu significantly improves patient quality of life. MP-AzeFlu is a currently available combination that may satisfy all these patient needs and expectations.

Suppression of LPS-Induced Inflammation and Cell Migration by Azelastine through Inhibition of JNK/NF-κB Pathway in BV2 Microglial Cells.

The c-Jun N-terminal kinases (JNKs) are implicated in many neuropathological conditions, including neurodegenerative diseases. To explore potential JNK3 inhibitors from the U.S. Food and Drug Administration-approved drug library, we performed structure-based virtual screening and identified azelastine (Aze) as one of the candidates. NMR spectroscopy indicated its direct binding to the ATP-binding site of JNK3, validating our observations. Although the antihistamine effect of Aze is well documented, the involvement of the JNK pathway in its action remains to be elucidated. This study investigated the effects of Aze on lipopolysaccharide (LPS)-induced JNK phosphorylation, pro-inflammatory mediators, and cell migration in BV2 microglial cells. Aze was found to inhibit the LPS-induced phosphorylation of JNK and c-Jun. It also inhibited the LPS-induced production of pro-inflammatory mediators, including interleukin-6, tumor necrosis factor-α, and nitric oxide. Wound healing and transwell migration assays indicated that Aze attenuated LPS-induced BV2 cell migration. Furthermore, Aze inhibited LPS-induced IκB phosphorylation, thereby suppressing nuclear translocation of NF-κB. Collectively, our data demonstrate that Aze exerts anti-inflammatory and anti-migratory effects through inhibition of the JNK/NF-κB pathway in BV2 cells. Based on our findings, Aze may be a potential candidate for drug repurposing to mitigate neuroinflammation in various neurodegenerative disorders, including Alzheimer's and Parkinson's diseases.

Efficacy of a Novel Intranasal Formulation of Azelastine Hydrochloride and Fluticasone Propionate, Delivered in a Single Spray, for the Treatment of Seasonal Allergic Rhinitis: Results from Russia.

BACKGROUND: The novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP) in a single spray (MP-AzeFlu) was compared with a first-line intranasal antihistamine spray (AZE) in Russian seasonal allergic rhinitis (SAR) patients. METHODS: Moderate-to-severe SAR/rhinoconjunctivitis patients (n = 149; aged 18-65 years) were randomized to receive MP-AzeFlu (137/50 µg AZE/FP per spray) or AZE (137 µg/spray), both as 1 spray/nostril twice daily, in a multicenter, open-label, 14-day, parallel-group trial. The primary outcome was change from baseline in morning and evening reflective total nasal symptom score (rTNSS). Secondary end points included: change from baseline in reflective total ocular symptom score (rTOSS), reflective total of 7 symptom scores (rT7SS), 28-item Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) overall score, and EuroQol-5D (EQ-5D) questionnaire score. RESULTS: When compared with AZE-treated patients, those treated with MP-AzeFlu experienced significantly greater reductions in rTNSS (difference: -2.47; 95% confidence interval [CI] -3.65 to -1.30; p < 0.001), rTOSS (difference: -1.62; 95% CI -2.32 to -0.92; p < 0.001), and rT7SS (difference: -4.34; 95% CI -5.98 to -2.70; p < 0.001). Superior relief observed on day 2 with MP-AzeFlu versus AZE was sustained throughout the study. MP-AzeFlu-treated patients experienced a greater improvement in QoL than AZE-treated patients as measured by overall RQLQ score (mean ± SD 2.91 ± 1.08 vs. 2.05 ± 1.15) and EQ-5D score (mean ± SD 87.4 ± 10.3 vs. 83.0 ± 12.8). MP-AzeFlu was well tolerated. CONCLUSIONS: MP-AzeFlu was superior to AZE in reducing moderate-to-severe SAR symptoms, providing earlier and more complete symptom relief.

MP29-02 reduces nasal hyperreactivity and nasal mediators in patients with house dust mite-allergic rhinitis.

BACKGROUND: Nasal hyperreactivity (NHR) is an important clinical feature of allergic rhinitis (AR). The efficacy of MP29-02 (azelastine hydrochloride (AZE) and fluticasone propionate [FP]) nasal spray on local inflammatory mediators and NHR in AR is unknown. We tested if MP29-02 decreases inflammatory mediators and NHR in AR and if this effect is due to restoration of nasal epithelial barrier function. METHODS: A 4-week double-blinded placebo-controlled trial with MP29-02 treatment was conducted in 28 patients with house dust mite (HDM) AR. The presence of NHR was evaluated by measuring reduction in nasal flow upon cold dry air exposure. The effects of AZE ± FP on barrier integrity and airway inflammation were studied in a murine model of HDM-induced NHR and on reduced activation of murine sensory neurons and human mast cells. RESULTS: MP29-02 but not placebo reduced NHR (P < .0001 vs P = .21), levels of substance P (P = .026 vs P = .941), and ß-hexosaminidase (P = .036 vs P = .632) in human nasal secretions. In wild-type C57BL6 mice, the reduction in ß-hexosaminidase levels (P < .0001) by AZE + FP treatment upon HDM challenge was found in parallel with a decreased transmucosal passage (P = .0012) and completely reversed eosinophilic inflammation (P = .0013). In vitro, repeated applications of AZE + FP desensitized sensory neurons expressing the transient receptor potential channels TRPA1 and TRPV1. AZE + FP reduced MC degranulation to the same extent as AZE alone. CONCLUSION: MP29-02 treatment reduces inflammatory mediators and NHR in AR. The effects of AZE + FP on MC degranulation, nasal epithelial barrier integrity, and TRP channels provide novel insights into the pathophysiology of allergic rhinitis.

Efficient UPLC and CE methods for the simultaneous determination of azelastine hydrochloride and its genotoxic impurity.

A novel stability-indicating UPLC and CE method was established and validated for the determination of azelastine hydrochloride (AZL) and its genotoxic impurity, benzohydrazide, in the presence of benzalkonium chloride. The developed UPLC method was based on chromatographic separation using a C18 column as a stationary phase and acetonitrile-(0.1% w/v) aqueous sodium lauryl sulfate (55:45, v/v, pH 5 with phosphoric acid) as a mobile phase with a flow rate of 1.2 mL/min and UV detection at 215 nm. The chromatographic run time was ~2 min. The developed CE method depended on using a stationary phase of Standard Bare Fused Silica Capillaries (75 µm i.d. × 59 cm and 50 cm detection length) and the applied voltage was 30 kV using 40 mm phosphate buffer (pH 2 with aqueous H3 PO4 ); the detection wavelength was 225 nm. The analysis time was about 6 min. The suggested methods were successfully applied for the analysis of AZL in a pharmaceutical preparation. The validity of the developed methods was assessed by applying the standard addition technique and no interference from excipients was observed. The results obtained by the proposed methods were statistically analyzed and compared with the manufacturer's method and no significant difference was found between the compared methods.

Effect of nasal antihistamine on secretory IgA in nasal lavage of rats.

The humoral IgA is an immunoglobulin which plays a defensive role for organisms on mucosal surfaces. Today, intranasal antihistamines are effectively used in the treatment of allergic rhinitis. In our study, the effect of azelastine hydrochloride-a nasal antihistaminic-on humoral IgA of the nasal mucosa has been reviewed empirically. Twenty-four female Sprague-Dawley rats were included in our study. The rats were divided into three groups randomly. Group 1(azelastine hydrochloride): rats in this group had nasal azelastine hydrochloride (0.05%) applied for 30 days at 10 µl/nostril dosage. Group 2 (saline): saline (0.09%) was applied to the rats in this group for 30 days at 10 µl/nostril dosage. Group 3 (control): no application was made throughout the study. The chemicals applied in Groups 1 and 2 were applied to both nostrils by mounting a flexible micropipette to the end of an insulin injector. At the beginning of the study, nasal lavage was performed to both nostrils of the rats in every group on the 15th and 30th day to aspirate irrigation solution (distilled water). The aspirated liquids were kept at - 80° temperature and reviewed together at the end of study. Within-group comparisons: in Group 1 (azelastine hydrochloride), the humoral IgA value on the 15th day was significantly higher than the basal value (p = 0.037). There is a significant difference between humoral IgA value on the 30th day and humoral IgA value on the 15th day (p = 0.045). In Group 2 (saline), no significant difference is available between basal, 15th day and 30th day humoral IgA values (p = 0.265). In Group 3 (control), no significant difference is available between basal, 15th day and 30th day humoral IgA values (p = 0.374). Between-group comparison: there is no significant difference in between-group humoral IgA basal values (p = 0.714). On days 15 and 30, Humoral IgA value of Group 1 was significantly higher than that of Groups 2 and 3 (p = 0.013, p = 0.024, respectively). According to the results we achieved in our study, nasal antihistaminic (azelastine hydrochloride) significantly increases the level of humoral IgA. Our study is the first one in the literature to reveal a relation between nasal antihistaminic and humoral IgA and there is a further need for clinical, randomized and prospective studies.

A Pilot Study Investigating Clinical Responses and Biological Pathways of Azelastine/Fluticasone in Nonallergic Vasomotor Rhinitis before and after Cold Dry Air Provocation.

BACKGROUND: Nonallergic vasomotor rhinitis (NAVMR) has been considered a diagnosis by exclusion due to unknown mechanisms or lack of diagnostic biomarkers. METHODS: To determine clinical responses and biological pathways in NAVMR subjects challenged to cold dry air (CDA) in an environmental exposure chamber (EEC) pre- and posttreatment with azelastine/fluticasone (AzeFlu), 30 NAVMR subjects, prescreened for CDA-induced symptoms (approx. 14°C, <15% relative humidity, ×1 h) were randomized to treatment with AzeFlu (n = 20) or placebo (n = 10) for 2 weeks. Total nasal symptoms scores, minimum cross-sectional area, cough, and conjunctival redness were recorded at visit 1 (pretreatment) and visit 2 (posttreatment) before, during, and after CDA challenge. At both visits, nasal lavage fluid (NLF) and nasal scrapings (NS) were collected pre- and post-CDA challenge. Substance P, neurokinin-A, and calcitonin gene-related peptide concentrations in NLF were analyzed pre- and postchallenge at each visit. Their relationship with CDA-induced symptoms was determined by statistical analysis. MicroRNA sequencing from NS determined differentially expressed miRNA between the treatment groups post-CDA challenge at each visit. RESULTS: The minimum cross-sectional area (p < 0.05), cough count (p < 0.05), and substance P (p < 0.01) improved posttreatment with AzeFlu versus placebo. Gene targets for differentially expressed miRNAs at visit 1 were enriched for biological pathways regulating epithelial ciliogenesis and cell integrity that were modified in the AzeFlu-treated group versus placebo posttreatment. CONCLUSIONS: This study demonstrated the feasibility of an EEC model to investigate CDA-induced clinical responses and pathobiology in NAVMR subjects pre- and posttreatment with AzeFlu. NAVMR disease mechanisms for other nonallergic triggers can be investigated similarly.

Validated sensitive spectrofluorimetric method for determination of antihistaminic drug azelastine HCl in pure form and in pharmaceutical dosage forms: application to stability study.

A highly sensitive, simple and rapid spectrofluorimetric method was developed for the determination of azelastine HCl (AZL) in either its pure state or pharmaceutical dosage form. The proposed method was based on measuring the native fluorescence of the studied drug in 0.2 M H2 SO4 at λem  = 364 nm after excitation at λex  = 275 nm. Different experimental parameters were studied and optimized carefully to obtain the highest fluorescence intensity. The proposed method showed a linear dependence of the fluorescence intensity on drug concentration over a concentration range of 10-250 ng/mL, with a limit of detection of 1.52 ng/mL and limit of quantitation of 4.61 ng/mL. Moreover, the method was successfully applied to pharmaceutical preparations, with percent recovery values (± SD) of 99.96 (± 0.4) and 100.1 (± 0.52) for nasal spray and eye drops, respectively. The results were in good agreement with those obtained by the comparison method, as revealed by Student's t-test and the variance ratio F-test. The method was extended to study the stability of AZL under stress conditions, where the drug was exposed to neutral, acidic, alkaline, oxidative and photolytic degradation according to International Conference on Harmonization (ICH) guidelines. Copyright © 2016 John Wiley & Sons, Ltd.

[The effectiveness of the combination of azelastine hydrochloride and mometasone furoate for the intranasal application in the patients presenting with seasonal allergic rhinitis]. / Éffektivnost' kombinatsii azelastina gidrokhlorida i mometazona furoata dlia intranazal'nogo primeneniia u bol'nykh sezonnym allergicheskim rinitom.

The objective of the present work was to evaluate the effectiveness of the combination of azelastine hydrochloride and mometasone furoate for the intranasal application to treat the patients presenting with seasonal allergic rhinitis. A total of 60 subjects suffering from seasonal allergic rhinitis were available for the observation. All the patients were allocated to three groups comprised of 20 individuals each. The patients of the first group received the fixed combination of azelastine hydrochloride and mometasone furoate for the intranasal application, those in the second group were given mometasone furoate administered intranasally together with an oral antihistamine preparation of the third generation, and the patients of the third group were treated with intranasal mometasone furoate alone. The effectiveness of the treatment was evaluated on days 7 and 14 after its initiation. It was found that the treatment with the use of the combination of azelastine hydrochloride and mometasone furoate resulted in a more pronounced alleviation of rhinological symptoms and improvement of the quality of life at the early stages of therapy in comparison with mometasone furoate monotherapy. It is concluded that the patients with moderate and severe seasonal allergic rhinitis can be recommended to use the combination of azelastine hydrochloride and mometasone furoate as качестве the initial treatment.

[Possibilities of azelastine in the treatment of chronic rhinitis]. / Vozmozhnosti azelastina v terapii khronicheskogo rinita.

There is considered modern classification of rhinitis and the accents in diagnostic and therapeutic approaches to patients with this disease are indicated, as well as the possibilities of using topical intranasal antihistamines in the treatment of allergic, vasomotor and medicamentous rhinitis.

Efficacy of MP-AzeFlu in children with seasonal allergic rhinitis: Importance of paediatric symptom assessment.

BACKGROUND: This study aimed to assess the efficacy of MP-AzeFlu (a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in a single spray) in children with seasonal allergic rhinitis (SAR) and explore the importance of child symptom severity assessment in paediatric allergic rhinitis (AR) trials. METHODS: A total of 348 children (4-11 years) with moderate/severe SAR were randomized into a double-blind, placebo-controlled, 14-day, parallel-group trial. Efficacy was assessed by changes from baseline in reflective total nasal symptom score (rTNSS), reflective total ocular symptom score (rTOSS) and individual symptom scores over 14 days (children 6-11 years; n = 304), recorded by either children or caregivers. To determine whether a by-proxy effect existed, efficacy outcomes were assessed according to degree of child/caregiver rating. Moreover, total Paediatric Rhinitis Quality of Life Questionnaire (PRQLQ) score was compared between the groups. RESULTS: A statistically superior, clinically relevant efficacy signal of MP-AzeFlu versus placebo was apparent for PRQLQ overall score (diff: -0.29, 95% CI -0.55, -0.03; p = 0.027), but not for rTNSS (diff: -0.80; 95% CI: -1.75; 0.15; p = 0.099). However, as the extent of children's self-rating increased, so too did the treatment difference between MP-AzeFlu and placebo; MP-AzeFlu provided significantly better relief than placebo for rTNSS (p = 0.002), rTOSS (p = 0.009) and each individual nasal and ocular symptom assessed (except rhinorrhoea; p = 0.064) when children mostly rated their own symptoms. CONCLUSIONS: MP-AzeFlu is an effective treatment for AR in childhood. Caregivers are less able than children to accurately assess response to treatment with available tools. A simple paediatric-specific tool to assess efficacy in AR trials in children is needed.

Fluticasone Propionate with Azelastine Versus Standalone Fluticasone Propionate as Nasal Spray in Allergic Rhinitis: A Prospective Comparative Study in a Rural Population of Northern India.

BACKGROUND: Allergic rhinitis (AR) is a symptomatic condition of the nose, caused by an IgE-mediated inflammation of the nasal membranes. Allergic rhinitis is further split into two categories, based on the duration of symptoms: intermittent (IAR) or persistent (PER) disease. Oral or topical antihistamines and topical nasal steroids are the most popular and efficient treatments for allergic rhinitis. METHODS: The present prospective comparative study was done between December 2021 to November 2022, with 64 subjects of PER divided into groups A and B. Group A patients received Fluticasone propionate (50 mcg) combined with Azelastine (140 mcg) nasal spray, whereas Group B patients received standalone Fluticasone propionate (50 mcg) nasal spray. RESULTS: In both groups, the difference in mean TSS between the beginning and end of the 4-week study period was statistically significant (p for both < 0.05). After 4 weeks of treatment, Group A had a TSS of 2.02 ± 0.83 and Group B was at 3.80 ± 1.49; the difference between them was statistically significant (p < 0.05). CONCLUSIONS: According to results obtained from the current study, while both fluticasone propionate with azelastine nasal spray and standalone fluticasone propionate nasal spray are widely used for control of symptoms in PER, the former offers better results with significant reduction of symptoms when compared to the latter.

Efficacy of Topical Azelastine and Fluticasone Dipropionate Combination in Children With Adenoid Hypertrophy.

OBJECTIVE: Adenoid hypertrophy (AH) is one of the common childhood diseases. Surgical and non-surgical treatment of AH in children is planned according to the severity of symptoms and associated complications. In recent years, treatment methods with intranasal sprays have been reported quite frequently in uncomplicated cases. We aim to evaluate the effectiveness of a new combination of azelastine - fluticasone (AZE-FLU) (137mcg azelastine and 50mcg fluticasone) nasal spray in children with uncomplicated AH. METHODS: Sixty-five children diagnosed with AH were included in the study. The mean age of the children was 7.42 ± 2.26 (4-13 years). The cohort consisted of 29 males and 36 females. All children were evaluated clinically and endoscopically. AZE-FLU nasal spray was applied to both nostrils twice a day for three months. Adenoid/choana ratio and symptom scores were evaluated before treatment and at the end of the 12th week. RESULTS: At the end of 24 weeks of AZE-FLU application, there was a statistically significant decrease in both adenoid/choana ratio and symptom scores. While the initial adenoid/choana (A/C) score was 3.57 ± 0.58, it decreased to 1.74 ± 0.61 following treatment. A dramatic decrease in total symptom scores was observed. The total symptom score average was 15.63 ± 1.28 before treatment, while it was 2.31 ± 1.4 after the treatment with the difference being statistically significant (P < .01). CONCLUSION: In this study, the effectiveness of AZE-FLU nasal spray on AH was investigated for the first time. This treatment provides an effective alternative to the surgical approach in children with uncomplicated adenoid hypertrophy. Using this protocol, 96% of patients were removed from the surgery list. LEVEL OF EVIDENCE: is IV.

Cytological Study of Topical Effect of Azelastine Hydrochloride on the Nasal Mucous Membrane Cells in Various Nasal Rhinitis Types.

Previous reports on the benefits of using local therapy with azelastine in rhinitis focus on the assessment of clinical symptoms and the analysis of nasal lavage for the presence of inflammatory cells and the expression of adhesion molecules. Little attention has been paid to studies assessing the effect of azelastine on individual cytotypes of the nasal mucosa, especially epithelial cells, also in the context of inducing morphological changes. The aim of this study was the cytological analysis of swabs taken from the surface of the nasal mucosa of patients with allergic rhinitis (AR) and nonallergic/vasomotor rhinitis (NAR/VMR) who were subjected to 4 weeks of therapy with azelastine and then comparing the obtained results with the pre-treatment condition. The technique of obtaining materials for cytoanalysis included sampling, staining of smears, microscopic analysis, and preparation of cytograms. Our studies confirmed the therapeutic benefits of azelastine in both study groups. Significant changes were demonstrated, confirming the regeneration of ciliated cells and the induction of autophagy and apoptosis in epithelial cells. Such changes indicate new mechanisms of action of azelastine, which play a significant role in restoring homeostasis in the nasal mucosa. The presented research also results in a detailed description of cytological changes in both studied rhinitis types, which complements the knowledge regarding prognostic indicators.

The Comparative Bioavailability of Fluticasone and Azelastine Delivered as a Single Fixed Dose Combination (MP-AzeFlu) in Comparison to Two Different Formulations of Azelastine and Fluticasone Propionate Following Intranasal Administration in Healthy Chinese Volunteers.

Objective: Two studies (Study I and Study II) were conducted in healthy Chinese volunteers to confirm that there was no pharmacokinetic drug interaction between AZE and FLU in MP-AzeFlu. The secondary objective was to evaluate the pharmacokinetic parameters of MP-AzeFlu compared with the commercially available mono-components. Methods: Both studies were a randomized, open-label, three-period, six-sequence, single-dose cross-over trial (William's design) conducted at Beijing Hospital (Beijing, China) in September and October of 2019 in 30 healthy adult male and female volunteers. The natural log transformed parameters: AUC0-tlast, AUC0-∞ and Cmax were analyzed. Results: The comparison of PK parameters between MP-AzeFlu and Aze (commercially available) showed that the LS mean ratios (90% CI) values for, AUC0-tlast, AUC 0-∞ and Cmax were 100.29% (94.31-106.66%), 100.76% (94.60-107.32%) and 93.14% (81.47-106.48%). The comparison of PK parameters between MP-AzeFlu and Flu (commercially available) for the bioavailability evaluation showed that the LS mean ratios (90% CI) values for, AUC0-tlast, AUC 0-∞ and Cmax were 83.48% (69.81-99.82%), 100.19% (87.34-114.94%) and 81.91% (68.50-97.95%). Conclusion: The study results confirm that neither the FLU or the AZE component in the combination product (MP-AzeFlu), nor the existing qualitative and quantitative differences in the formulation between the currently marketed AZE and FLU mono-product, display significant potential to impact the systemic exposure of AZE or FLU in Chinese subjects.

Antiviral Potential of Azelastine against Major Respiratory Viruses.

The Coronavirus Disease 2019 (COVID-19) pandemic and the subsequent increase in respiratory viral infections highlight the need for broad-spectrum antivirals to enable a quick and efficient reaction to current and emerging viral outbreaks. We previously demonstrated that the antihistamine azelastine hydrochloride (azelastine-HCl) exhibited in vitro antiviral activity against SARS-CoV-2. Furthermore, in a phase 2 clinical study, a commercial azelastine-containing nasal spray significantly reduced the viral load in SARS-CoV-2-infected individuals. Here, we evaluate the efficacy of azelastine-HCl against additional human coronaviruses, including the SARS-CoV-2 omicron variant and a seasonal human coronavirus, 229E, through in vitro infection assays, with azelastine showing a comparable potency against both. Furthermore, we determined that azelastine-HCl also inhibits the replication of Respiratory syncytial virus A (RSV A) in both prophylactic and therapeutic settings. In a human 3D nasal tissue model (MucilAirTM-Pool, Epithelix), azelastine-HCl protected tissue integrity and function from the effects of infection with influenza A H1N1 and resulted in a reduced viral load soon after infection. Our results suggest that azelastine-HCl has a broad antiviral effect and can be considered a safe option against the most common respiratory viruses to prevent or treat such infections locally in the form of a nasal spray that is commonly available globally.