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Fluticasone and budesonide inhibit cytokine release in human lung epithelial cells and alveolar macrophages.

Ek A, Larsson K, Siljerud S, Palmberg L.

Department of Occupational Medicine, National Institute for Working Life, Solna, Sweden.

Glucocorticoids are potent anti-inflammatory agents capable of influencing cytokine release in a number of cell types. The aim of the present study was to investigate whether glucocorticoids, frequently used in the treatment of asthma, interfere with cytokine secretion by lung epithelial cells and alveolar macrophages in vitro. Inhalation of swine dust induces airway inflammation with influx of inflammatory cells and release of proinflammatory cytokines in the lungs. Therefore, human lung epithelial cells (A549) and human alveolar macrophages were stimulated with swine dust or lipopolysaccharide (LPS), and the inhibitory effect of budesonide and fluticasone propionate on cytokine release was studied in a dose-response (10(-13)-10(-8) M) manner. The time course for the steroid effect was also investigated. Both steroids caused a dose-dependent, almost total, inhibition of swine dust-induced IL-6 and IL-8 release from epithelial cells and LPS-induced IL-6 and TNF-alpha from alveolar macrophages. The steroids only partially inhibited IL-8 release from alveolar macrophages. Budesonide was approximately 10 times less potent than fluticasone propionate. Preincubation with the steroids did not inhibit cytokine release more than simultaneous incubation with stimulus and steroid. In conclusion, budesonide and fluticasone propionate, in concentrations that probably occur in the airway lining fluid during inhalational therapy, inhibited cytokine release from human lung epithelial cells (IL-6, IL-8) and alveolar macrophages (TNF-alpha, IL-6, IL-8). In vitro, the onset of this effect was rapid.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10442524&dopt=Abstract fluticasone Flonase



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Pharmaceutical properties of fluticasone propionate nasal drops: a new formulation.

Denyer S.

Department of Pharmacy, School of Pharmacy and Biomolecular Sciences, University of Brighton, UK.

A variety of corticosteroid delivery systems have been considered for the treatment of nasal polyposis. Safety considerations favour local delivery of the drug to the nasal cavity. No topical delivery system is entirely without problems, however, and formulations must address issues of microbiological quality, drug stability, reproducible drug delivery and adequate drug distribution at site, while also offering environmental and patient acceptability. Fluticasone propionate has been formulated in a new nasal drop preparation. As a highly water-insoluble compound, the active fluticasone propionate requires micronization to an optimal particle size and subsequent dispersion with a surface-active wetting agent. The product is presented in a unit dose low-density polyethylene container, manufactured by a blow-fill-seal process and stored in an aluminium foil overwrap. Micronized active has been used to promote optimal local drug delivery, and excipients have been selected for low irritancy potential and high formulation stability. There is no microbiological risk with fluticasone propionate unit dose nasal drops 400 microg and therefore no need to include a preservative in the preparation. They provide a convenient and effective treatment option for patients with nasal polyposis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10442546&dopt=Abstract fluticasone Flonase



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The cost-effectiveness of inhaled fluticasone propionate and budesonide in the treatment of asthma in adults and children.

Barnes NC, Thwaites RM, Price MJ.

Department of Respiratory Medicine, London Chest Hospital, U.K.

Inhaled corticosteroids form the mainstay of the treatment and management of asthma and the results of a meta-analysis comparing two of the most frequently prescribed inhaled corticosteroids, fluticasone propionate and budesonide, administered in a clinically equivalent 1:2 dose ratio to 1980 patients with asthma, demonstrated that fluticasone propionate had an improved efficacy:safety ratio. However, limited data are available on the relative economic benefits of fluticasone propionate and budesonide. The database for clinically relevant parameters, for which the efficacy:safety meta-analysis had demonstrated statistical significance between the two corticosteroids, was used for this pharmacoeconomic analysis. Treatment with fluticasone propionate was more cost-effective than budesonide with respect to improvement in morning peak expiratory flow rate, successfully treated weeks, symptom-free days, symptom-free 24 h and episode-free days. The costs of treatment for fluticasone propionate and budesonide were 7.78 Pounds per week and 12.33 Pounds per week, respectively. The main contributing factor to the higher costs of budesonide was the higher cost of health care contacts, which were 4.53 Pounds per week for budesonide and 0.57 Pounds per week for fluticasone propionate. The pharmacoeconomic difference increased in favour of fluticasone propionate as the criteria for success were made more stringent. These results demonstrate that, for asthma patients requiring modification of therapy treatment with fluticasone propionate is more effective and also cheaper, in terms of overall health-care costs, than treatment with budesonide.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10464822&dopt=Abstract fluticasone Flonase



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Effects of high-dose inhaled corticosteroids on plasma cortisol concentrations in healthy adults.

Brus R.

IntroGene BV, Leiden, the Netherlands.

BACKGROUND: Recent studies suggest that inhaled corticosteroids may differ significantly in their systemic effects. OBJECTIVE: To compare the systemic effects, as measured by plasma cortisol suppression, of inhaled beclomethasone dipropionate, budesonide, flunisolide, fluticasone propionate, and triamcinolone acetonide at doses of approximately 1000 microg twice daily. METHODS: Sixty healthy adult male volunteers participated in this randomized, open-label, parallel-design study. Twenty-four-hour plasma cortisol determinations (cortisol-AUC24) were measured after a single dose of placebo medication and after a single dose and 7 consecutive doses of active medication. RESULTS: After a single dose, all inhaled corticosteroid preparations caused statistically significant mean reductions in cortisol-AUC24 compared with placebo as follows: flunisolide, 7% (P= .02); budesonide, 16% (P= .001); beclomethasone, 18% (P= .003); triamcinolone, 19% (P=.001); and fluticasone, 35% (P<.001). After multiple doses, flunisolide was not significantly different from placebo (5%; P = .24), while budesonide (18%; P = .002), triamcinolone (25%; P<.001), beclomethasone (28%; P<.001), and fluticasone (79%; P<.001) all resulted in statistically significant suppression of cortisol-AUC24. After both single and multiple doses, beclomethasone, budesonide, flunisolide, and triamcinolone were not statistically different from each other, while fluticasone was significantly (P<.001) more suppressive than the other 4 medications. CONCLUSIONS: These results indicate that there are differences in the systemic effects of inhaled corticosteroids when used in high doses and emphasize the importance of using the minimum dose of inhaled corticosteroids required to maintain control of asthma symptoms.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10493320&dopt=Abstract fluticasone Flonase



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Effect of fluticasone propionate and salmeterol on Pseudomonas aeruginosa infection of the respiratory mucosa in vitro.

Dowling RB, Johnson M, Cole PJ, Wilson R.

Host Defence Unit, Imperial College of Science, Technology and Medicine at the National Heart and Lung Institute, London, UK.

The purpose of this study was to investigate the effect of the corticosteroid, fluticasone propionate (FP), on Pseudomonas aeruginosa infection of the respiratory mucosa of an organ culture model in vitro. Organ cultures infected with P. aeruginosa had significantly (p< or =0.05) elevated levels of mucosal damage and significantly (p< or =0.05) less ciliated cells compared to controls. Preincubation of tissue with FP (10(-6) or 10(-5) but not 10(-7) M) prior to P. aeruginosa infection significantly (p< or =0.05) reduced the bacterially induced mucosal damage in a concentration-dependent manner. FP (10(-5) M) also significantly (p< or =0.05) prevented loss of ciliated cells. FP did not alter the density of bacteria adherent to the different mucosal features of the organ cultures, but did reduce total bacterial numbers due to the reduced amount of damaged tissue, which is a preferred site of P. aeruginosa adherence. It has previously been shown that the long-acting beta2-agonist salmeterol (4 x 10(-7)M) also reduces the mucosal damage caused by P. aeruginosa infection, probably via elevation of intracellular cyclic adenosine monophosphate concentrations. Preincubation of tissue with both 10(-7)M FP and 10(-7)M salmeterol, concentrations at which they did not by themselves influence the effect of P. aeruginosa infection, significantly (p< or =0.05) reduced P. aeruginosa-induced loss of cilia. However, there was no additional benefit from adding 4 x 10(-7)M salmeterol to 10(-6)M FP. In conclusion fluticasone propionate reduced mucosal damage caused by P. aeruginosa infection in vitro and preserved ciliated cells. There was a synergistic action with salmeterol in the preservation of ciliated cells.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10515415&dopt=Abstract fluticasone Flonase