Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Mometasone Furoate”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1991

Cytokine inhibition by a novel steroid, mometasone furoate.

Mometasone furoate (9 alpha, 21 dichloro-11 beta, 17 alpha dihydroxy-16 alpha methyl-1,4 pregnadiene-3, 20 dione-17-[2'] furoate) was an unexpectedly potent inhibitor of the in vitro production of three inflammatory cytokines, IL-1(1), IL-6, and TNF-alpha. The potency of mometasone furoate in inhibiting cytokine production was compared to that of hydrocortisone, betamethasone, dexamethasone, and beclomethasone. IL-6 and TNF-alpha were both produced by WEHI-265.1 (murine myelomonocytic leukemia) cells following stimulation by lipopolysaccharide (LPS). Twenty-four hours after stimulation by LPS, the cell-free supernatant fluids were removed. Their cytokine content was analyzed using ELISAs specific for each cytokine. IL-1 synthesis was induced in the harvested peritoneal macrophages of BALB/c mice by incubation with LPS for twenty-four hours. The IL-1 content in the cell-free supernatant fluids was determined by the thymocyte-costimulator bioassay. Using these systems, mometasone furoate was found to be the most potent steroid tested for inhibiting the production of the three cytokines. The IC50's were 0.05 nM (IL-1), 0.15 nM (IL-6), and 0.25 nM (TNF-alpha). The inhibition of the production of proinflammatory mediators by extremely low concentrations of mometasone furoate suggests that this steroid should be highly effective in various disorders.

Administration, Topical↗
PubMed2004

Characterization of degradation products of mometasone furoate.

Mometasone furoate (MF) is a synthetic glucocorticoid with anti-inflammatory activity, which is used for the treatment of topical skin disorders, allergic rhinitis and treatment of mild to moderate persistent asthma. The focus of this study is to examine the stability of MF in simulated lung fluid (SLF) and to clearly identify the structure of the degradation products of MF by MS and NMR analysis. Mometasone furoate degradation leads to the formation of two products, D1 and D2 with significant pH dependence. The half-lives for the conversion of MF to D1 and subsequent conversion of D1 to D2 at 37 degrees C in SLF were 1.3 and 4.8 h respectively. LC-MS and NMR analysis confirmed that D1 is 9,11-epoxide mometasone furoate while D2 represents a new chemical structure that shows cyclization within the C17-C21 region. The biological activity of these degradation products was assessed in rat lung glucocorticoid receptor binding studies. D1 showed 4 fold greater receptor affinity to glucocorticoid receptors compared to dexamethasone. However, the receptor affinity for D2 was a log order lower than that for dexamethasone. The instability of MF in SLF resulted in two degradation products, one of the degradation products showing glucocorticoid receptor activity, the other representing a new cyclized structure whose pharmacological properties have not been described. The biological significance of these degradation products is unknown.

Animals↗
PubMed2005

Nasal allergies and beyond: a clinical review of the pharmacology, efficacy, and safety of mometasone furoate.

Mometasone furoate nasal spray (MFNS; Nasonex, Schering-Plough Corporation, Kenilworth, NJ, USA) is an effective and well-tolerated intranasal corticosteroid approved for the prophylactic treatment of seasonal allergic rhinitis, and the treatment of perennial allergic rhinitis. MFNS is a potent molecule with a rapid onset of action and excellent safety and efficacy profiles. Having recently received approval for the treatment of nasal polyposis, data indicate that MFNS may also be effective in rhinosinusitis.

Anti-Allergic Agents↗
PubMed2004

Human receptor kinetics, tissue binding affinity, and stability of mometasone furoate.

Mometasone furoate (MF) is a topically used glucocorticoid with high anti-inflammatory potency. In contrast to the wealth of data derived from clinical studies, information about the molecular pharmacology of the compound is lacking or contradictory. Thus, we elucidated the characteristics of receptor binding kinetics and receptor affinity in a bioassay. Metabolite formation was determined in human plasma and lung tissue as well as binding affinity to human lung tissue. Fast and extensive association of MF to the human glucocorticoid receptor was observed while the dissociation of the MF-receptor complex was faster compared to fluticasone propionate (FP). The relative receptor affinity of MF was calculated as 2200 (dexamethasone = 100, FP = 1800) and confirmed in a bioassay measuring the induction of the glucocorticoid regulated protein CD163 in human monocytes. In plasma and human lung tissue MF formed a 9,11-epoxy degradation product. The binding affinity of MF to human lung tissue was low compared to FP due to fast redistribution from tissue into plasma. These molecular pharmacological properties are in accordance with clinical data.

Antigens, CD↗
PubMed2004

Significant receptor affinities of metabolites and a degradation product of mometasone furoate.

Mometasone furoate (MF) is a highly potent glucocorticoid used topically to treat inflammation in the lung, nose and on the skin. However, so far no information has been published on the human glucocorticoid receptor activity of the metabolites or degradation products of MF. We have now determined the relative receptor binding affinities of the known metabolite 6beta-OH MF and the degradation product 9,11-epoxy MF to understand their possible contribution to undesirable systemic side effects. In competition experiments with human lung glucocorticoid receptors we have determined the relative receptor affinities (RRA) of these substances with reference to dexamethasone (RRA = 100). We have discovered that 6beta-OH MF and 9,11-epoxy MF display RRAs of 206 +/- 15 and 220 +/- 22, respectively. This level of activity is similar to that of the clinically used inhaled corticosteroid flunisolide (RRA 180 +/- 11). Furthermore we observed that 9,11-epoxy MF is a chemically reactive metabolite. In recovery experiments with human plasma and lung tissue we found a time dependent decrease in extractability of the compound. Hence, we provide data that might contribute to the understanding of the pharmacokinetics as well as the clinical effects of MF.

Biodegradation, Environmental↗
PubMed2004

Adrenal suppression with dry powder formulations of fluticasone propionate and mometasone furoate.

Mometasone furoate (MF) and fluticasone propionate (FP) are high potency inhaled corticosteroids. The systemic bioavailability of MF is claimed to be negligible, leading to a minimal potential for systemic adverse effects. We assessed the overnight urinary cortisol/creatinine as the primary outcome of adrenal suppression in 21 patients with persistent asthma (mean FEV1 = 91%). Patients were randomized in a crossover fashion to receive 2 weekly consecutive doubling incremental doses of either FP Accuhaler (500, 1,000, and 2,000 microg/day) or MF Twisthaler (400, 800, and 1,600 microg/day). For the 21 per protocol completed patients, there was significant suppression of overnight urinary cortisol/creatinine with high and medium doses of both drugs-as geometric mean fold suppression (95% confidence interval) from baseline: FP 2,000 microg, 1.85 (1.21-2.82, p = 0.002); FP 1,000 microg, 1.45 (1.07-1.96, p = 0.02); MF 1,600 microg, 1.92 (1.26-2.93, p = 0.001); and MF 800 microg, 1.39 (1.04-1.88, p = 0.02). For secondary outcomes of 8:00 A.M. plasma cortisol, serum osteocalcin, and early morning urinary cortisol/creatinine, there was significant suppression with MF and FP at the highest dose. Our data refute the assertion that MF has negligible systemic bioavailability and a lower potential for systemic adverse effects compared with FP.

Administration, Inhalation↗
PubMedDate not supplied

Mometasone furoate 0.1%-salicylic acid 5% ointment versus mometasone furoate 0.1% ointment in the treatment of moderate-to-severe psoriasis: a multicenter study.

Topical corticosteroids and keratolytics are both used widely in the management of patients with psoriasis. A combination of the two types of agents may provide enhanced relief. The purpose of this study was to compare the efficacy and safety of the combination ointment mometasone furoate 0.1% plus salicylic acid 5% with that of mometasone furoate 0.1% ointment in the treatment of moderate-to-severe psoriasis vulgaris. A total of 408 patients were enrolled in this controlled, randomized, double-masked, parallel-group, multicenter comparison. Patients applied either mometasone furoate-salicylic acid ointment or mometasone furoate ointment alone to target lesions twice daily for 21 days. Severity of erythema, induration, and scaling were scored at baseline and at days 4, 8, 15, and 22. An evaluation of overall change in disease status of all treated lesions was performed at each follow-up visit. Adverse events were also monitored and scored, including signs of skin atrophy. Beginning on day 8, the combination of mometasone furoate-salicylic acid was significantly more effective than mometasone furoate alone, as indicated by the mean percentage of improvement in total disease scores, mean total disease sign scores, and the individual score for scaling. Similarly, the combination was more effective beginning on day 15, as indicated by the global evaluation of overall clinical response and individual scores for erythema and induration. Both treatments were well tolerated. Mometasone furoate-salicylic acid ointment provides more effective treatment of moderate-to-severe psoriasis than does mometasone furoate ointment alone and is safe and well tolerated.

Administration, Topical↗
PubMed1998

Anti-inflammatory activity of inhaled mometasone furoate in allergic mice.

Mometasone furoate (CAS 83919-23-7, Sch 32088) is a new inhaled corticosteroid that is being developed to treat allergic inflammatory airway disorders such as rhinitis and asthma. In this study, we investigated the effects of inhaled mometasone furoate in allergic mice that, after antigen challenge, develop an influx of eosinophils and T cells and display an increased mRNA expression of proinflammatory cytokines in the lungs. Mometasone furoate aerosol was generated from metered dose inhalers and delivered into an animal exposure chamber. The mice were exposed to mometasone furoate by nose-only inhalation at respired doses ranging from 0.5-33 micrograms/kg given 24, 18 and 2 h before aeroallergen challenge. The elevated eosinophil numbers in the bronchoalveolar lavage fluid and lung tissues of sensitized, ovalbumin challenged mice were dose-dependently inhibited by inhaled mometasone furoate. Increased numbers of Thy1+ T cells and CD4+ (T-helper) and CD8+ (T-cytotoxic) T cell subsets were seen in the bronchoalveolar lavage fluid of ovalbumin-challenged mice. Pretreatment of these animals with mometasone furoate (33 micrograms/kg) reduced the number of Thy1+ T cells and the T-helper subset. Furthermore, mometasone furoate (33 micrograms/kg) reduced the percentage of CD44+ T-helper cells (activated/memory cells) to the levels observed in non-sensitized, ovalbumin-challenged mice. There were increased levels of steady-state mRNA for interleukin-4, interleukin-5, and to a lesser extent, gamma-interferon in the lungs of sensitized mice after ovalbumin challenge and pretreatment with mometasone furoate reduced the steady-state mRNA levels of these cytokines. Our results demonstrate a potent lung anti-inflammatory effect of inhaled mometasone furoate and identify that inhibition of T cell influx, eosinophil accumulation and modulation of cytokine activity are important components of this response.

Administration, Inhalation↗
PubMed2005

Solid state characterization of mometasone furoate anhydrous and monohydrate forms.

Mometasone furoate is a potent glucocorticoid anti-inflammatory agent. Its anhydrous Form 1 and monohydrate form were characterized by X-ray crystallography, X-ray powder diffraction at ambient and elevated temperature, thermal analysis, FT-IR, and dynamic moisture adsorption. In Form 1, mometasone furoate molecules pack tightly with molecules interlocked in a space group of P2(1)2(1)2(1). The monohydrate form crystallizes in space group P1. The unit cell of the monohydrate contains one water molecule and one mometasone furoate molecule. The water molecules form channels along the a axis and mometasone furoate molecules pack in layers in the same direction. Dehydration was observed between 60 and 100 degrees C by thermogravimetric analysis with a heating rate of 10 degrees C/min. It corresponds to a broad endotherm over the same temperature range in the differential scanning calorimetry with the same heating rate. Variable temperature X-ray powder diffraction reveals that a new anhydrous form (Form 2) was fully produced above 90 degrees C. This crystalline form was converted to Form 1 after being heated above 150 degrees C; and was totally converted to the monohydrate after 1 day at 23 degrees C, 45% RH.

Anti-Inflammatory Agents↗
PubMed1998

Mometasone furoate. A review of its intranasal use in allergic rhinitis.

UNLABELLED: Mometasone furoate is a synthetic corticosteroid which has been evaluated for intranasal use in the treatment of adults and children with allergic rhinitis. In several large, well-controlled clinical trials, mometasone furoate 200 micrograms administered once daily as an aqueous intranasal spray was significantly more effective than placebo in controlling the symptoms associated with moderate to severe seasonal or perennial allergic rhinitis. Mometasone furoate was as effective as twice-daily beclomethasone dipropionate or once-daily fluticasone propionate in the treatment of perennial allergic rhinitis, and was as effective as twice-daily beclomethasone dipropionate and slightly more effective than once-daily oral loratadine in the treatment of seasonal allergic rhinitis. Mometasone furoate was also as effective as twice-daily beclomethasone dipropionate or once-daily budesonide, and significantly more effective than placebo in the prophylaxis of seasonal allergic rhinitis. The onset of action of mometasone furoate was approximately 7 hours in patients with seasonal allergic rhinitis. Mometasone furoate was as well tolerated as beclomethasone dipropionate, fluticasone propionate and budesonide in clinical trials, with an overall incidence of adverse events similar to placebo. Adverse events were generally mild to moderate and of limited duration. The most common adverse events associated with mometasone furoate therapy were nasal irritation and/or burning, headache, epistaxis and pharyngitis. Intranasal or oral mometasone furoate had no detectable effect on hypothalamic-pituitary-adrenal axis function in studies of < or = 1 year in duration. CONCLUSIONS: Mometasone furoate is a well tolerated intranasal corticosteroid with minimal systemic activity and an onset of action of < or = 7 hours. It is effective in the prophylaxis and treatment of seasonal allergic rhinitis and the treatment of perennial allergic rhinitis in patients with moderate to severe symptoms.

Anti-Allergic Agents↗
PubMed2001

Inhaled mometasone furoate: a review of its use in adults and adolescents with persistent asthma.

UNLABELLED: Mometasone furoate is a corticosteroid with relatively high in vitro potency. Recent randomised, double-blind, multicentre trials have assessed the efficacy of mometasone furoate delivered by dry powder inhaler over 12 weeks in adults and adolescents with mild to severe persistent asthma. Mometasone furoate 200 microg twice daily or 400 microg once daily in the morning or 200 microg once daily in the evening improved lung function, asthma symptom scores and use of rescue medication to a significantly greater extent than placebo in patients who had previously received only short-acting inhaled beta2-adrenoceptor agonists alone as treatment in 3 trials (n = 195 to 306). In studies in 227 to 733 patients with mild to moderate asthma who were receiving ongoing treatment with inhaled corticosteroids prior to enrolment, mometasone furoate 100 to 400 microg twice daily was consistently better at improving the above indicators of asthma than placebo. Mometasone furoate 100 to 200 microg twice daily was as effective as beclomethasone dipropionate 200 microg twice daily or budesonide 400 microg twice daily and mometasone furoate 200 microg twice daily was as effective as fluticasone propionate 250 microg twice daily. Mometasone furoate 400 or 800 microg twice daily was also consistently more effective than placebo in reducing oral corticosteroid dosages and improving lung function and asthma symptoms in 132 patients with oral corticosteroid-dependent asthma. Once daily administration of mometasone furoate 400 microg appears to be as effective at improving indicators of asthma as twice daily administration of 200 microg. Patients receiving mometasone furoate < or =800 microg/day and recipients of placebo experienced a similar overall incidence of adverse events considered to be related to treatment. The most common of these events were oral candidiasis, headache, pharyngitis and dysphonia. Mometasone furoate 100 to 400 microg twice daily, beclomethasone dipropionate 200 microg twice daily, budesonide 400 microg twice daily or fluticasone propionate 250 microg twice daily were similarly tolerated. CONCLUSION: Inhaled mometasone furoate is well tolerated, with minimal systemic activity and is equally effective when administered as a divided dose or as a single daily dose. Use of the drug can result in a decrease in requirements for oral corticosteroids in patients with oral corticosteroid-dependent asthma and is as effective as other inhaled corticosteroids currently used in the treatment of mild to moderate persistent asthma. Thus mometasone furoate is suitable for the control of mild to severe persistent asthma in adults or adolescents.

Administration, Inhalation↗
PubMed2006

Effects of treatment with mometasone furoate dry powder inhaler in children with persistent asthma.

BACKGROUND: Mometasone furoate dry powder inhaler (DPI) has been shown to effectively treat asthma in children. OBJECTIVE: To evaluate the efficacy and safety of 2 dosing regimens of mometasone furoate DPI in the treatment of mild-to-moderate persistent asthma in children previously using inhaled corticosteroids (ICSs). METHODS: A 12-week, multicenter, double-blind, parallel-group, placebo-controlled study evaluated 2 dosing regimens of mometasone furoate DPI (100 microg every evening and 100 microg twice daily) in 296 children 4 to 11 years old with asthma previously using ICSs. The primary efficacy variable was the change in percentage of predicted forced expiratory volume in 1 second (FEV1) from baseline to end point. Secondary efficacy variables included absolute FEV1, forced expiratory flow between 25% and 75% forced vital capacity, morning and evening peak expiratory flow, asthma symptom scores, albuterol use, nocturnal awakenings, response to therapy, and health-related quality of life. RESULTS: Mean changes from baseline at end point in predicted FEV1 were 4.73 and 5.52 percentage points for mometasone furoate DPI, 100 microg every evening and 100 microg twice daily, respectively, the difference of which was not significant, and -1.77 percentage points for placebo (P < or = .002). Significant improvements in secondary efficacy variables were also observed for both mometasone furoate DPI treatments over placebo. Both mometasone furoate DPI doses were well tolerated, and no significant differences were noted among the 3 treatment groups in adverse event reporting. CONCLUSIONS: Both mometasone furoate DPI doses were well tolerated and significantly improved lung function, maintained effective asthma control, and improved quality of life in children with asthma.

Abdominal Pain↗
PubMed2003

Degradation kinetics of mometasone furoate in aqueous systems.

Mometasone furoate (MF) is a synthetic glucocorticoid. There is little information available on the stability of MF and no degradation products have been unequivocally identified. Thus, the primary objective of this study was to characterize the degradation of MF, qualitatively and quantitatively. Stability of MF decreased with increasing pH (>4) and decreasing ionic strength in aqueous media. The chemical stability of MF in aqueous systems was significantly dependent on pH. MF appeared to be stable at pH < 4 but degraded to four products at higher pH. The degradation of MF in aqueous solutions follows pseudo-first-order kinetics and involved a series of parallel and consecutive reactions. The turnover of MF and its products appears to be catalyzed by the hydroxide ion. The pH dependence of these reactions should be considered, when formulating or extemporaneously compounding MF formulations. An optimal pH of stability was below pH 4. The changes in pH, however, do not appear to be the only factor of importance, since an increase in ionic strength and buffer concentration displayed a stabilizing effect on this glucocorticoid in the buffers tested. Trace metal ions are unlikely to be involved in degradation of MF in aqueous solution.

Buffers↗
PubMed1999

Short-term lower leg growth rate in children with rhinitis treated with intranasal mometasone furoate and budesonide.

BACKGROUND: Mometasone furoate (MF) aqueous nasal spray is a potent intranasal glucocorticoid with low systemic bioavailability. Knemometry has been shown to be a sensitive method of detecting systemic effects of exogenous steroids in children. OBJECTIVE: We sought to assess whether MF (100 or 200 microg) or budesonide intranasal aqueous spray (400 microg) influences the short-term lower leg growth rate in children with seasonal or perennial allergic rhinitis. METHODS: MF, budesonide, and placebo were administered once daily for 2 weeks to 22 children aged 7 to 12 years (mean, 10 years) in a randomized, double-blind, crossover study. Lower leg measurements were done before and after each 2-week treatment period. Two-week washout intervals separated each treatment period. RESULTS: There were no significant differences in lower leg growth rates among the MF 200 microg (0.95 +/- 0.79 mm; mean +/- SD), budesonide 400 microg (0.73 +/- 0.61 mm), or placebo (0.69 +/- 0.70 mm) groups. The growth rate of the group receiving a 100-microg dose of MF (1.16 +/- 0.67 mm) was greater than that for the group receiving placebo (P =.024) or budesonide (P =.033). No statistically significant sequence effect (P =.11), carry-over effect (P =.24), overall treatment effect (P =.086), or period effect (P =.065) was detected. CONCLUSION: No short-term adverse effects on linear lower leg growth rates were detected after once daily MF or budesonide at clinically relevant doses.

Administration, Intranasal↗
PubMed1996

Once-daily mometasone furoate aqueous nasal spray (Nasonex) in seasonal allergic rhinitis: an active- and placebo-controlled study.

Mometasone furoate aqueous nasal spray (Nasonex) was compared with beclomethasone dipropionate (BDP) aqueous nasal spray in a double-blind, randomized, placebo-controlled, double-dummy, parallel-group study of adults with moderate to severe seasonal allergic rhinitis. Patients allergic to at least one tree and/or grass aeroallergen received one of the following regimens for up to 4 weeks; mometasone furoate 100 micrograms once daily [OD] (n = 126) or 200 micrograms OD (n = 126), BDP 200 micrograms twice daily (n = 126), or only placebo spray (n = 123). Physician-rated nasal and total symptom scores, and global evaluation of overall condition and therapeutic response by physicians and patients, showed that the three active treatments were equally effective, and all three were significantly superior to placebo at most time points. Overall, mometasone furoate 200 micrograms OD demonstrated somewhat greater numerical, but not statistical, superiority to mometasone furoate 100 micrograms OD at the earliest evaluation time point. At the end of treatment, complete or marked relief was obtained in 77% of patients with mometasone furoate 100 micrograms/day, 79% with mometasone furoate 200 micrograms/day, and 74% with BDP, compared with 54% of placebo vehicle control patients. Mometasone furoate and BDP were equally well tolerated. It was concluded that mometasone furoate adequately controls symptoms of moderate to severe seasonal allergic rhinitis, offers the advantage of OD treatment, and is well tolerated.

Administration, Inhalation↗
PubMed2001

A review of the pharmacology and pharmacokinetics of inhaled fluticasone propionate and mometasone furoate.

BACKGROUND: Fluticasone propionate is an established corticosteroid administered intranasally for the treatment of rhinitis or by oral inhalation for the treatment of asthma. Mometasone furoate, a closely related corticosteroid currently available in an intranasal formulation, is being investigated in an oral inhalation formulation for the treatment of asthma. OBJECTIVE: This article reviews available data on the comparative structure-activity relationships, chemistry, pharmacology, pharmacokinetics, and systemic bioavailability of fluticasone propionate and mometasone furoate to assess whether claims of differences in the absolute systemic bioavailability of the 2 compounds are supported by the published literature. METHODS: Information for this review was identified through a MEDLINE search of the literature from 1966 to the present that contained the term mometasone or fluticasone. The resulting list was narrowed by excluding articles dealing with dermatologic applications. A systematic review was conducted of the identified literature pertaining to the molecular structure, topical potency, lipophilicity, pharmacokinetics, and bioavailability of the 2 agents. Additionally, the pharmacology of the 2 moieties was assessed by a review of the available literature on receptor binding affinity, transactivation and transrepression potency, and inhibition of inflammatory-cell cytokine expression. RESULTS: Based on the available data, fluticasone propionate and mometasone furoate have similar physicochemical properties and structure-activity relationships. When administered intranasally, mometasone furoate is reported to have comparable relative systemic bioavailability to that of fluticasone propionate (mean plasma area under the curve, 123 pmol x h/L vs 112 pmol x h/L, respectively). When administered as a single dose by dry powder inhaler, orally inhaled fluticasone propionate is reported to have a total systemic bioavailability of approximately 17%, whereas that of mometasone furoate is reported to be < 1%. However, the mometasone furoate bioavailability study that reported the latter value used lower drug doses and a less sensitive assay than the fluticasone propionate bioavailability study. When multiple-dose data were used, mometasone furoate had an estimated 11% systemic bioavailability, similar to that of fluticasone propionate. CONCLUSIONS: Inhaled fluticasone propionate and mometasone furoate appear to have comparable potential systemic absorption and, based on the total systemic bioavailabilities of the parent compounds, have a low potential for systemic side effects at the recommended clinical doses. However, in the case of mometasone furoate, the contribution of the active metabolites to systemic effects has not been adequately assessed.

Administration, Intranasal↗