Comparative clinical pharmacology of mometasone furoate, fluticasone propionate and fluticasone furoate.

AIMS: To investigate the pharmacokinetics and effects on the hypothalamic-pituitary-adrenal (HPA) axis of mometasone furoate (MF), fluticasone propionate (FP) and fluticasone furoate (FF). METHODS: Study 1: Fourteen healthy participants received inhaled and intravenous MF (inhaled dose via Twisthaler) and FP (inhaled dose via Diskus), both given at 400 µg, using a randomised, single-dose, four-way crossover design. Study 2: Twenty-seven participants with mild to moderate asthma, who discontinued their corticosteroid medication for 5 days to obtain a baseline 24 h serum cortisol, received inhaled MF Twisthaler and FP Diskus, both given at 400 µg twice daily (BID), using a randomised, 14-day repeat dose, two-way crossover design. Study 3: Forty-four healthy participants were randomised to a double-blind, placebo-controlled, five-period crossover study where the following treatments were administered via the inhaled route for 7 days: FP Diskus (250, 500, 1000 µg BID), FF Diskus (100, 200, 400, 800, 1600 µg once daily [QD]) or placebo Diskus. In each study, 24-h serial blood samples were collected and assayed to assess concentrations of MF, 6ß-hydroxy mometasone, mometasone, FP, FF and cortisol. Pharmacokinetic and serum cortisol parameters were estimated as geometric means and 95% confidence intervals (CI). RESULTS: Study 1: For intravenous MF and FP, respectively: absolute bioavailability was 11.4% (95% CI: 7.5, 17.6) and 7.8% (6.3, 9.6); plasma clearance was 47 L/h (41, 52) and 60 L/h (52, 69); half-life was 7.4 h (6.9, 8.0) and 7.2 h (6.5, 8.0); and volume of distribution was 499 L (439, 567) and 623 L (557, 698). Inhalation of single dose MF or FP did not significantly affect serum cortisol (<10% reduction from baseline), whereas intravenous administration of MF or FP each changed serum cortisol by approximately -50% from baseline. Study 2: For MF and FP, respectively: area under the curve up to the last measurable concentration on Day 1 was 421 pg h/mL (270, 659) and 248 pg h/mL (154, 400), and on Day 14 was 1092 pg h/mL (939, 1269) and 591 pg h/mL (501, 696); absolute bioavailability was 12.8% (11.2, 14.2) and 8.9% (7.7, 10.2). On Day 14, 24-h serum cortisol change from baseline was -35% (-44%, -26%) and -18% (-28%, -5%) for MF and FP, respectively; the reduction was significantly greater for MF than FP (ratio for geometric adjusted mean serum cortisol concentration: 1.28 [1.04, 1.56]). Low plasma concentrations of 6ß-hydroxy mometasone were detected after intravenous dosing (Study 1) and after multiple inhaled dosing (Study 2); mometasone was not detected in any samples. Study 3: Inhaled FP and FF had similar systemic bioavailability estimates (12.0% [11.0, 13.2] and 15.0% [12.0, 17.3], respectively), but a differential effect on the HPA axis which was in agreement with the known 1.7-fold higher glucocorticoid receptor-binding affinity of FF versus FP. However, for FP 250 µg BID and FF 100, 200 and 400 µg QD, reduction in serum cortisol was not significantly different from placebo. For higher doses, FP 500 and 1000 µg BID, and FF 800 and 1600 µg QD, changes in serum cortisol concentration relative to placebo were -30%, -70%, -41% and -90%, respectively. Repeat inhaled dosing of FP 1000 µg/day (within the therapeutic dose range) resulted in comparable cortisol suppression to MF in the therapeutic range (30% reduction); whereas for FF this occurred at more than 3-fold above the therapeutic dose range (644 µg/day). CONCLUSIONS: Single inhaled and intravenous doses of MF and FP (400 µg) resulted in similar bioavailability and reductions in serum cortisol. Repeat dosing of inhaled MF and FP in the therapeutic range (800 µg/day) resulted in greater systemic exposure for MF, and a 35% reduction in serum cortisol that was 2-fold greater than for FP. The higher glucocorticoid receptor-binding affinity and bioavailability, lower clearance and the presence of active metabolites may contribute to the greater systemic exposure and effect on cortisol for MF. Repeat dosing of inhaled FP and FF resulted in similar systemic bioavailability but differed in terms of the dose required for comparable cortisol suppression to MF in the therapeutic range. Unlike FP and FF, MF has active metabolites that may contribute to its systemic effects, while device/formulation performance differences also exist between MF-containing products.

Fitting Pharmacodynamic Data to the Emax Model to Assess the Inherent Potency of Topical Corticosteroids.

The widespread use of topical corticosteroids (TCs) in dermatotherapy requires a consideration of their potency and benefit/risk ratios. Although there are a variety of topical corticosteroid products (TCPs) available on the market and their potencies are ranked using different classification systems, to our knowledge, no classification system to rank the inherent potencies of TC active pharmaceutical ingredients (APIs) currently exists. Most of the published classification systems for TCPs are based on randomized clinical comparative studies and/or vasoconstrictor assay (VCA) data. The objective was to apply the US FDA's VCA to classify the inherent potencies of several TCs using standardized doses to make appropriate comparisons of the relevant APIs in solutions of the same molar concentrations. Six TC APIs were assessed for their relative potencies using healthy human participants. The Emax model was used to fit skin blanching data following application of the respective TCs, and the parameters, Emax and ED50, were derived. Emax values were used as the metric to assess potency. Statistical analyses of the data revealed that the inherent potencies of fluticasone propionate, mometasone furoate, and hydrocortisone butyrate were similar. However, there was no significant difference between hydrocortisone butyrate and clobetasol propionate, while there was a significant difference between clobetasol propionate, fluticasone propionate, and mometasone furoate. Hence, the potency of hydrocortisone butyrate appears to overlap two potency classes. Furthermore, the potencies of betamethasone valerate and methylprednisolone aceponate were similar but lower than those of all of the other APIs. The application of the VCA to classify inherent potency provides a reliable method to establish a classification system for TCs. Inherent potency assessment of TCs provides information that will be useful when choosing an appropriate TC for the development of a TCP for a specific clinical indication.

Application of Emax model to assess the potency of topical corticosteroid products.

The objective of this study was to compare the potencies of two topical corticosteroid products (TCPs) using the Emax model to fit the skin blanching responses obtained from the US FDA's vasoconstrictor assay (VCA) and to illustrate the influence of formulation on potency. The potencies of two marketed TCPs, Dermovate® cream containing clobetasol propionate (CP) and Elocon® cream containing mometasone furoate (MF), were assessed using healthy human subjects. In order to investigate the influence of formulation and associated vehicle properties, the creams were compared with their respective topical corticosteroids (TCs) from a previously published study wherein the inherent potencies of those TCs were assessed using a validated VCA method. Whereas the inherent potency of MF (Emax = -94.45 ± 0.21) was found to be greater than CP (Emax = -58.80 ± 15.65), when formulated as creams, the TCP containing CP had a higher potency (Emax = -86.15 ± 0.17) than that containing MF (Emax = -42.61 ± 26.04). This reversal of potency may be attributed to the effect of formulation factors. The comparison of the potencies of TCPs with inherent potencies of their corresponding TCs confirmed the influence of formulation parameters on the potency of those products.

[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.

Indacaterol, glycopyrronium, and mometasone: Pharmacological interaction and anti-inflammatory profile in hyperresponsive airways.

LABA/ICS and LABA/LAMA/ICS combinations elicit beneficial effects in asthma. Specific evidence concerning the impact of combining indacaterol acetate (IND), glycopyrronium bromide (GLY), and mometasone furoate (MF) on human airway hyperresponsiveness (AHR) and airway inflammation is still missing. The aim of this study was to characterize the synergy of IND/MF and IND/GLY/MF combinations, both once-daily treatments for asthma, in hyperresponsive airways. Passively sensitized human medium and small airways were stimulated by histamine and treated with IND/MF (molar ratio: 100/45, 100/90) and IND/GLY/MF (molar ratio: 100/37/45, 100/37/90). The effect on contractility and airway inflammation was tested. Drug interaction was assessed by Bliss Independence equation and Unified Theory. IND/MF 100/90 elicited middle-to-very strong synergistic relaxation in medium and small airways (+≈20-30% vs. additive effect, P < 0.05), for IND/MF 100/45 the synergy was middle-to-very strong in small airways (+≈20% vs. additive effect, P < 0.05), and additive in medium bronchi (P > 0.05 vs. additive effect). IND/GLY/MF 100/37/45 and 100/37/90 induced very strong synergistic relaxation in medium and small airways (+≈30-50% vs. additive effect, P < 0.05). Synergy was related with significant (P < 0.05) reduction in IL-4, IL-5, IL-6, IL-9, IL-13, TNF-α, TSLP, NKA, SP, and non-neuronal ACh, and enhancement in cAMP. IND/MF and IND/GLY/MF combinations synergistically interact in hyperresponsive medium and small airways and modulate the levels of cytokines, neurokinins, ACh, and intracellular cAMP. The concentrations of MF in the combinations modulate the effects in the target tissue.

Indacaterol/Glycopyrronium/Mometasone: A Review in Asthma.

Indacaterol/glycopyrronium/mometasone (Enerzair® Breezhaler®) is a fixed-dose combination of the long-acting ß2 agonist (LABA) indacaterol, the long-acting muscarinic antagonist (LAMA) glycopyrronium and the inhaled corticosteroid (ICS) mometasone furoate (hereafter referred to as mometasone) delivered via a capsule-based dry-powder inhaler. It is approved in the EU for use as maintenance treatment in adult patients with inadequately controlled asthma who had experienced one or more exacerbations in the previous year. The approval also includes an optional digital companion (sensor and app) that provides data on the patient's use of the inhaler. In the 52-week IRIDIUM trial in patients with inadequately controlled asthma, indacaterol/glycopyrronium/mometasone improved lung function to a greater extent than LABA/ICS combinations (i.e. indacaterol/mometasone and fluticasone propionate/salmeterol), but superiority in Asthma Control Questionnaire 7 score was not shown. In the 24-week ARGON trial, indacaterol/glycopyrronium/mometasone via a single inhaler was non-inferior to fluticasone propionate/salmeterol + tiotropium via two inhalers with regard to Asthma Quality of Life Questionnaire score. Indacaterol/glycopyrronium/mometasone was generally well tolerated, and the most common adverse events were respiratory in nature. In conclusion, combination therapy with indacaterol/glycopyrronium/mometasone represents a valuable option for the maintenance treatment of asthma, with the convenience of once-daily administration via a single inhaler.

Asthma is a chronic inflammatory lung disease characterized by repeated episodes of wheezing, breathlessness, coughing and chest tightness. Some patients with asthma have inadequately controlled disease despite treatment with an inhaled corticosteroid (ICS) and a long-acting ß₂ agonist (LABA). The addition of a long-acting muscarinic antagonist (LAMA) may provide further benefit, but has traditionally required the use of two separate inhalers. Indacaterol/glycopyrronium/mometasone (Enerzair^® Breezhaler^®) is the first fixed-dose LABA/LAMA/ICS combination for asthma therapy. It is administered once daily using a single inhaler. There is also an optional digital sensor that attaches to the base of the device to collect data on the use of the inhaler by the patient. Indacaterol/glycopyrronium/mometasone improved lung function to a greater extent than LABA/ICS combinations in adult patients with inadequately controlled asthma who had experienced one or more exacerbations in the previous year. Indacaterol/glycopyrronium/mometasone was generally well tolerated. The most common adverse events were respiratory-related. Combination therapy with indacaterol/glycopyrronium/mometasone is a valuable, convenient option for the maintenance treatment of asthma.

P-glycoprotein inhibition with verapamil overcomes mometasone resistance in Chronic Sinusitis with Nasal Polyps.

BACKGROUND: P-glycoprotein (P-gp) is a membrane efflux pump which is overexpressed in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) and promotes Type 2 inflammation. Glucocorticoids (GC) are substrates of P-gp suggesting that overexpression may additionally contribute to GC resistance in CRSwNP. This study aims to determine whether P-gp inhibition using verapamil enhances mometasone retention and efficacy in nasal polyp explants. METHODOLOGY: IRB approved study in which organotypic polyp explants were exposed to mometasone (4.15 µg/mL) and verapa- mil (125 µg/mL) as mono and combination therapy. The effect of verapamil on mometasone tissue retention over time was deter- mined using HPLC. The effect of verapamil on mometasone anti-inflammatory function was determined using ELISA for secreted IL-5. Groups were compared using Kruskal-Wallis test. RESULTS: P-gp expression strongly and significantly inversely correlated with mometasone retention 1hr after exposure, with a ne- arly 6-fold reduction in tissue retention between the lowest and highest P-gp expressing polyp explants. P-gp inhibition reversed this effect and significantly improved mometasone retention at 1hr relative to mometasone alone. The combination of mome- tasone and verapamil significantly reduced IL-5 secretion relative to vehicle control and outperformed either treatment alone. CONCLUSIONS: Our study confirms that P-gp contributes to mometasone resistance. This P-gp mediated resistance was successfully reversed by addition of the P-gp inhibitor verapamil. Verapamil further significantly enhanced the anti-inflammatory effect of mometasone when given as a combination therapy.

Study on the Slow-Release Mometasone Furoate Injection of PLGA for the Treatment of Knee Arthritis.

PURPOSE: The purpose of this study is to develop a new PLGA based formulation for microspheres, which aims to release mometasone furoate for one month, so as to improve compliance. METHODS: The microspheres containing mometasone furoate were prepared by oil in water emulsion and solvent evaporation. The microspheres were characterized by surface morphology, shape, size and encapsulation efficiency. The release in vitro was studied in 37°C phosphate buffer, and in vivo, pharmacodynamics and preliminary safety evaluation were conducted in male Sprague Dawley rats. RESULTS: The morphology results showed that the microspheres have a smooth surface, spherical shape and an average diameter of 2.320-5.679µm. The encapsulation efficiency of the microspheres loaded with mometasone furoate was in the range of 53.1% to 95.2%, and the encapsulation efficiency of the microspheres could be greatly affected by the proportion of oil phase to the water phase and other formulation parameters. In vitro release kinetics revealed that drug release from microspheres was through non-Fick's diffusion and PLGA polymer erosion. Pharmacokinetic data showed that the initial release of microspheres was small and then sustained. The results of the pharmacodynamics study fully proved the long-term effectiveness of mometasone furoate microspheres. The results of in vivo safety evaluation showed that the preparation system possessed good in vivo safety. CONCLUSION: This study shows that the microspheres prepared in this study have sufficient ability to stable drug release at least for 35 days, with good efficacy and high safety. In addition, mometasone furoate can be used as a potential candidate drug for 35 days long-term injection.

Mometasone furoate sinus implant - a new targeted approach to treating recurrent nasal polyp disease.

Introduction: Chronic rhinosinusitis (CRS) is a broad heterogeneous inflammatory disorder of the nose and paranasal sinuses, resulting from the dysfunctional interplay between host immunity, defective epithelial barrier, and environmental factors. CRS with nasal polyps (CRSwNP) is considered a more severe clinical phenotype with greater burden of symptoms and higher relapse rate, especially with comorbid asthma or aspirin sensitivity. Available treatment options after endoscopic sinus surgery (ESS) - systemic corticosteroids or revision surgery - have significant risks and limitations. Areas covered: Bioabsorbable, steroid-eluting implants have been studied extensively for the ability to dilate and re-establish sinus patency by the localized, controlled delivery of topical corticosteroids to diseased sinonasal lining and nasal polyps. This review provides a comprehensive, up to date analysis of the literature regarding a novel, office-based, mometasone furoate (MF) sinus implant that may treat patients with recurrent CRSwNP after ESS. Expert commentary: Clinical evidence has demonstrated the safety and efficacy of steroid-eluting implant in the reduction of polyp size, symptom burden, and the need for revision sinus surgery. MF sinus implants may play an important role in the management of patients with recurrent polyposis after sinus surgery.

Mometasone furoate inhibits growth of acute leukemia cells in childhood by regulating PI3K signaling pathway.

OBJECTIVES: Acute lymphoblastic leukemia (ALL) is the most common cancer before the age of 15 years, seriously endangering the health of children. The main treatment for Childhood ALL was pharmacotherapy. But these drugs have many side effects and some of them could develop drug resistance quickly. Mometasone furoate (MF) is an efficient glucocorticoid for topical treatment of inflammation on the skin, lung and nose. METHODS: In this study, we investigated whether the MF had effects on ALL cells proliferation and migration. RESULTS: The CCK-8 proliferation test showed that the cell viability was the lowest at 25 nM MF treatment and the increased OD value was time-dependent. In transwell assay, the number of CCRF-CEM cells was reduced in MF treated group. We found the expression of anti-apoptotic protein bcl-2 decreased the expression of pro-apoptotic protein caspase3 and bax increased in CCRF-CEM cell line treated with MF. The expression of p-AKT, p-mTOR, p70S6 K, vascular endothelial growth factor and CyclinD1 were decreased in MF treated group. CONCLUSION: This study reveals that MF can inhibit proliferation and invasion/migration and induce apoptosis in Childhood ALL cells, which may be regulated by Phosphatidylinositol 3-kinase signaling pathway. These results suggest MF may be a potential new drug target for clinical ALL treatment.

Effectiveness of quercetin in an experimental rat model of allergic rhinitis.

We aimed to investigate whether quercetin had a therapeutic effect in an experimental rat model of allergic rhinitis. The study was conducted with 35 rats, which were randomly assigned into 4 groups: group 1 (n = 5), sham group; group 2 (quercetin group, n = 10) received 80 mg/kg day quercetin; group 3 (steroid group, n = 10) received steroid (mometasone furoate); and group 4 (control group, n = 10), received ovalbumin alone. Rats were sensitized by administration of ovalbumin on alternate days over 14 days via an intraperitoneal route. On day 15, in addition to ovalbumin via an intranasal route, quercetin and steroid were given over 7 days to the corresponding groups. All rats were then sacrificed and nasal turbinates were evaluated histopathologically, and serum total IgE and ovalbumin (OVA)-specific IgE values were measured before and after treatment. A significant increase in OVA-specific IgE values was detected in all groups except sham group. A significant increase was detected in post-treatment total IgE levels in the control group, while no significant change was detected in the sham, quercetin, and intranasal steroid groups. On histopathological evaluation, it was observed that findings of allergic rhinitis were suppressed in the quercetin group when compared to the control group. In immunohistochemical evaluation, it was detected that COX-2 and VIP expressions were weaker in the quercetin group compared to the control group. Based on these findings, we conclude that quercetin was effective in allergic rhinitis induced by ovalbumin in rats both histopathologically and serologically.

Topical safety and vasoconstrictive assay-based bioequivalence of a new reformulated mometasone cream.

OBJECTIVES: A new improved mometasone furoate (Elocon™) cream with an emulsification system that produces a stable emulsion has been developed. In order to register the product in various markets, it was essential to ensure the cream was topically well tolerated and that it was bioequivalent to the reference product. METHODS: Phase I clinical studies were performed to assess the local safety and tolerability upon multiple dosing of this new cream as well as to assess the single-dose bioequivalence relative to the marketed product. Bioequivalence was assessed using a vasoconstrictive assay (VCA) after a dose-duration pilot study was completed with the marketed Elocon cream. KEY FINDINGS: The new mometasone cream and its vehicle were nonirritating in healthy subjects during 21-day patch application (MCII <0.025). The positive control was moderately irritating in the same study. The pivotal VCA study enrolled 162 subjects with 105 detectors included in the analysis of bioequivalence. In the 105 detectors, the ratio (×100%) of AUEC values at ED50 for test vs. standard (90% CI) was 112.91% (105.55, 120.87), within the bioequivalence criteria of (80, 125). CONCLUSIONS: These studies supported the registration of reformulated mometasone cream in various markets.

Antibiofilm effects of topical corticosteroids and intranasal saline in patients with chronic rhinosinusitis with nasal polyps depend on bacterial species and their biofilm-forming capacity.

Microbial biofilms have been implicated in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). Intranasal application of corticosteroids and saline is a reliable option for their management. The aim of our study was to evaluate in vitro antibiofilm effects of corticosteroids and isotonic and hypertonic nasal saline in CRSwNP patients. The sinus mucosal specimens were harvested from the ethmoid cavity of 48 patients with CRSwNP and further subjected to hematoxylin-eosin staining and microbiology analysis. The biofilm-forming capacity of isolated bacterial strains was detected by microtiter-plate method and the effects of therapeutic doses of mometasone, fluticasone, isotonic and hypertonic saline on biofilm production were investigated. Bacterial strains were isolated in 42 (87.5%) patients: one organism in 34 (80.9%) and two organisms in 8 (19.1%). Staphylococcus epidermidis (34%) and Staphylococcus aureus (28%) were the most prevalent bacteria in biofilms of CRSwNP patients. Corticosteroids and saline solutions significantly reduced biofilm formation (p < 0.01 and p < 0.05, respectively) with better efficacy of fluticasone and isotonic nasal saline. Treatment with fluticasone, mometasone, isotonic and hypertonic nasal saline completely prevented biofilm production in 66, 50, 84 and 38% of bacterial strains, respectively. The most significant density reduction was observed in biofilm formed by Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pneumoniae compared to other bacterial species (p < 0.01, p < 0.05, p < 0.05, respectively). The antibiofilm effects of corticosteroids and saline solutions also greatly depended on bacterial biomass (p < 0.05), with the most significant effect on high compared to small amount of formed biofilm. The topical steroids and nasal saline are shown to be potent antibiofilm agents in patients with CRSwNP. The effects of tested compounds depend on bacterial species and volume of formed biofilm.

Intranasal azelastine and mometasone exhibit a synergistic effect on a murine model of allergic rhinitis.

PURPOSE: The purpose of this study was to compare the anti-allergic effects of the combination of azelastine and mometasone with those of either agent alone in a Dermatophagoides farinae (Derf)-induced murine model of allergic rhinitis (AR). MATERIALS AND METHODS: Forty BALB/c mice were divided into five groups: azelastine (A), mometasone (M), a combination of azelastine and mometasone (MA), Derf, and control. Derf served as the allergen. Allergic symptom scores, eosinophil counts, and serum Derf-specific IgE levels were measured. The mucosal levels of mRNAs encoding interferon (IFN)-γ, T-bet, interleukin (IL)-4, GATA-3, Foxp3, IL-17, and ROR-γt were determined by real-time polymerase chain reaction. The T-bet, GATA-3, Foxp3, and ROR-γt results were confirmed by Western blotting. RESULTS: Nose-rubbing motions; the levels of mRNAs encoding IL-4, GATA-3, and ROR-γt; and tissue eosinophil count were reduced in the MA compared with those in the Derf group (all P values <0.05). The levels of mRNAs encoding GATA3 and IL-4 mRNA [synthesized by T helper (Th)2 cells] were reduced and that of mRNA encoding Foxp3 was increased in the MA compared with those in the Derf and A groups. Western blotting confirmed these findings. CONCLUSION: We found that the combination of intranasal azelastine and mometasone synergistically suppressed Th17 responses and (reciprocally) elevated Treg responses. Therefore, this combination not only ameliorated allergic inflammation by suppressing Th2 responses, but also usefully modified the Treg/Th17 balance.

Combination of mometasone furoate and oxymetazoline for the treatment of adenoid hypertrophy concomitant with allergic rhinitis: A randomized controlled trial.

In the clinic, approximately 30% of children with adenoid hypertrophy (AH) concomitant with allergic rhinitis (AR) report poor responses to intranasal steroids. To determine whether the combination of mometasone furoate (MF) and oxymetazoline (OXY) is more effective than either agent alone, we performed a two-stage, parallel, randomized, double-blind, double-dummy, clinical trial with 240 AH children with concomitant perennial AR. During the first stage, all children were randomly assigned to the MF or control group for six weeks of treatment. During the second stage, the non-responders from stage one were randomly assigned to 4 groups for 8 weeks of treatment that involved receiving the following treatments: MF/OXY, MF/placebo, placebo/OXY, or placebo/placebo. During the first stage of treatment, 39% of the responders treated with MF achieved greater reductions in total and individual symptom scores than did those on placebo. During the second stage of treatment, the nasal congestion scores of the MF/OXY group significantly decreased. The adenoid/choana ratio of the MF/OXY-treated group decreased and the nasal volume increased significantly. Our results suggest that the combination of OXY and MF is effective and safe for the treatment of AH children with concomitant AR and has a rapid onset of action.

[The use of intranasal glucocorticosteroids in the treatment of rhinosinusitis: Focus on mometasone furoate]. / Intranazal'nye glyukokortikosteroidy v terapii rinosinusita: fokus na mometazona furoat.

The authors discuss the mechanism of action, effectiveness, and safety of intranasal glucocorticosteroids (inGCS) used to treat acute, recurrent and chronic rhinosinusitis (RS). The last version of the European guidelines concerning the application of inGCS assigns the highest level of evidence-Ia and the highest strength of recommendations-A to these medications when applied for the treatment of acute and polypoid rhinosinusitis. Moreover, they acquire the status of the agents of choice for the therapy of chronic RS without polyps. Mometasone furoate is one of the best explored preparations of this group of medicines. It is possessed of favourable pharmacodynamic and pharmacokinetic properties when prescribed for local application. The new mometasone furoate preparation in the form of an intranasal spray Dezrinit produced by "Teva" Ltd. was registered in the Russian Federation. In a comparative randomized clinical trial (RCT), the preparation was shown to be an equivalent to the Nasonex spray.

Mometasone furoate nasal spray for the treatment of asthma.

INTRODUCTION: Asthma is a common respiratory disease characterized by airway inflammation, bronchoconstriction and airway hyperresponsiveness and symptoms such as coughing, wheezing, shortness of breath and chest tightness. Allergic rhinitis is a common comorbidity in asthma and glucocorticoids are the key stone in the treatment of both diseases. Mometasone furoate is a potent synthetic steroid with a very high receptor affinity and a low bioavailability and shown to be superior compared to other inhaled corticosteroids. It is not clear whether the use of mometasone furoate nasal spray (MFNS) is associated with an improvement in asthma control. AREAS COVERED: This current paper reviews the current knowledge on the effect of mometasone furoate nasal spray in the treatment of asthma and includes clinical trials in which both subjective and objective outcomes are assessed. EXPERT OPINION: To date, only few clinical studies have investigated the effect of nasal steroids in the treatment of asthma. The studies investigating the effect of MFNS report contradicting results, although the most well-designed study to answer this question finds no improvement in asthma control. Thus, it seems unlikely that asthma guidelines will be influenced by the current knowledge on the effect of MFNS in the treatment of asthma.

[Polypous rhinosinusitis in the children].

We present an overview of the modern literature concerningpolypous rhinosinusitis (PRS) in the children. The information thus derived is compared with the available results of the clinical investigations involving the adults patients with this pathology. Allergic diseases and mucoviscidosis appear to be the pathological conditions most likely leading to the development of polyps in the nasal cavity. The patients suffering from rhinosinusitis associated with the disorders of arachidonic acid metabolismare very rarely encountered in the pediatric practice unlike those among the adult population. Intranasal glucocorticosteroids (INGCS), especially in the form of the mometasonefuroate nasal spray, are considered to be the most promising medications for the treatment of the children presenting with PRS. However, further clinical studies are needed to confirm the effectiveness and safety of this therapeutic modality.

[The modern strategies for the treatment of allergic rhinitis].

The present literature review had the objective to analyze the published data concerning the effectiveness of intranasal administration of antihistamine preparations and intranasal glucocorticoids for the treatment of allergic rhinitis. Special emphasis is placed on the clinical significance and the further prospects for the application of a fixed combination of these medications including azelastineplusmometasonefuroateas the first choice therapy of moderately severe and severe manifestations of allergic rhinitis.

Comparison of Histopathological Effects of Thymoquinone and Local Nasal Corticosteroids in Allergic Rhinitis in a Rabbit Model.

BACKGROUND/AIMS: In this study, we aimed to evaluate the histopathological effects of thymoquinone treatment of the nasal mucosa in a rabbit model of allergic rhinitis, and we compared its effects with those of nasal mometasone furoate. METHODS: A total of 24 male New Zealand rabbits were used. The animals were randomly assigned to one of four groups. Group 1 received no treatment, while group 2 underwent ovalbumin (OVA) sensitization only. Group 3 was the study group; after OVA sensitization, the rabbits were treated with intranasal thymoquinone. The group 4 rabbits received mometasone furoate for 7 days after OVA sensitization. Mucosal structures were stained with hematoxylin and eosin, while toluidine blue was used to stain mast cells. Apoptosis was evaluated using a TUNEL assay. RESULTS: In the positive control groups, including the thymoquinone and intranasal mometasone furoate groups, intraepithelial and submucosal inflammation and goblet cell hypertrophy were significantly decreased compared to group 2 (p < 0.001). The cilial structure was normal, as was the chondrocyte structure in both treatment groups. CONCLUSION: This is the first study to evaluate the histopathological effects of thymoquinone in an allergic rhinitis model. Thymoquinone reduced allergic inflammation and may be valuable for treating allergic rhinitis. However, additional studies are needed.