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Fluticasone Propionate (fluticasone + propionate)

Distribution by Scientific Domains

Medical Sciences	91%
Chemistry	8%

Distribution within Medical Sciences

Respiratory Medicine	32%
Pharmacology & Pharmaceutical Medicine	18%
Allergy & Clinical Immunology	14%
5 Other Subdomains	22%

Selected Abstracts

Improved safety with equivalent asthma control in adults with chronic severe asthma on high-dose fluticasone propionate

RESPIROLOGY, Issue 3 2001
Norbert Berend
Objective: High-dose inhaled corticosteroids (ICS) have been associated with the same side-effects as oral corticosteroids. Beclomethasone dipropionate (BDP) and budesonide (BUD) in doses greater than 2000 ,g/day are used regularly in severe asthma, despite the fact that safety and efficacy data at such high doses are limited. Fluticasone propionate (FP) has been promoted as being twice as potent clinically as BDP or BUD at doses of 2000 ,g/day or less with a similar safety profile. The aim of this study was to compare the efficacy and safety of FP with BDP and BUD in 133 symptomatic adult asthmatics requiring at least 1750 ,g/day of BDP or BUD. Methodology: Patients fulfilling the entry criteria were randomized to receive either their regular ICS medication or FP at approximately half the microgram dose for 6 months in an open, parallel group study. The primary efficacy measure was based on morning peak expiratory flow measurements recorded by patients on daily record cards, while determination of safety was based on a number of endpoints including changes in bone turnover indices, the incidence of topical side-effects and assessments of quality of life. Results: It was shown that patients who were switched to FP, but not those continuing with BDP or BUD, had significant increases in levels of morning serum cortisol and the urine cortisol:creatinine ratio while maintaining asthma control. Serum osteocalcin and the pyridinoline:creatinine ratio, as well as the deoxypyridinoline:creatinine ratio, were also shown to increase only in the FP group. Subjective assessments such as quality of life score, the incidence and ease of bruising, and reports of hoarseness also favoured the FP group. Conclusions: It is concluded that, at the doses studied and with the delivery devices used clinically, FP is at least as effective as BDP/BUD in the management of severe asthma and may offer clinical advantages with respect to steroid-related adverse effects. [source]

A randomized double-blind study to compare the effects of nasal fluticasone and betamethasone on the hypothalamo,pituitary,adrenal axis and bone turnover in patients with nasal polyposis

CLINICAL OTOLARYNGOLOGY, Issue 6 2002
P.D. Fowler
Treatment of nasal polyposis with topical betamethasone is associated with suppression of the hypothalamo,pituitary,adrenal (HPA) axis and, potentially, has adverse effects on bone turnover. Fluticasone propionate is a potent corticosteroid with negligible absorption across the nasal mucosa and extensive first-pass hepatic metabolism. We performed a randomized double-blind study, in patients with nasal polyposis, comparing the effects of 8 weeks' treatment with betamethasone drops or fluticasone nasules on the HPA axis using the 1 µg tetracosactide test, and on bone turnover using two serum markers. Nine patients were allocated to each treatment. Betamethasone resulted in significant suppression in the tetracosactide test (P = 0.006), but fluticasone did not (P = 0.113). There were no differences in bone turnover or treatment efficacy between treatments. Treatment of nasal polyposis with topical betamethasone drops, but not with fluticasone nasules, suppresses the HPA axis and, given comparable efficacy, fluticasone administered via nasule should be the preferred agent. [source]

Cough after inhalation of corticosteroids delivered from spacer devices in children with asthma

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2003
Jean-Christophe Dubus
Abstract Children using a spacer device rather than another device for delivering inhaled corticosteroids (ICS) has been identified as a risk factor for cough immediately after inhalation. The aim of this study was to point out the different factors influencing the occurrence of such lateral side-effects. We studied this local side-effect in 402 asthmatic children (55.6 ± 34.9 months; 65.6% boys) treated for at least 1 month with beclomethasone dipropionate (n = 331), budesonide (n = 47) or fluticasone propionate (n = 24) delivered from pressurized metered-dose inhalers and small (75.1%) or large volume (24.8%) spacer devices mainly used with face mask (90.7%). A total of 219 patients (54.5%), treated with either high doses of ICS or ICS and long-acting ,2-agonist, were considered as having severe asthma. Cough was reported after each inhalation of corticosteroids in 216 patients (53.7%). Among them, about 30% also complained of cough with ,2-agonists. Despite different propellants and dispersants, all corticosteroids induced cough similarly. Cough was not linked with asthma severity, but was significantly related to therapy duration and use of long-acting ,2-agonist. Type and volume of the spacer device, use of a face mask or mouthpiece were not influencing factors. Cough after inhalation of corticosteroids delivered from spacer devices is a frequent local side-effect in children with asthma. This side effect can greatly alter compliance. A practitioner must be sought at each visit. [source]

An interesting case of colocalization of segmental lichen planus and vitiligo in a 14-year-old boy

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 8 2002
Kabir Sardana MD
A 14-year-old boy had segmental vitiligo (L3,4) on the right thigh and leg for 4 years, and was advised to apply topical clobetasol propionate, 0.05%, in the night, with daily sun exposure for 10 min, as he refused to comply with topical psoralens. As there was no response to therapy even after 3 months, the patient stopped the steroid cream but continued with the sun exposure. Subsequently, the patient noticed gradual-onset, itchy, violaceous, pigmented, raised lesions superimposed on the vitiligo macules. Cutaneous examination revealed violaceous, polygonal papules, 0.5 × 0.5 cm in size, some of which coalesced to form discrete violaceous plaques, confined to areas of vitiligo, with a clear-cut demarcation from normal skin (Fig. 1). The scalp, palms, soles, nails, and mucosa were normal. Histopathology of the polygonal papules revealed hyperkeratosis, wedge-shaped hypergranulosis, irregular acanthosis with saw toothing of the rete ridges, basal cell liquefaction, and a band-like lymphocytic infiltrate (Fig. 2), consistent with lichen planus. The patient was subsequently prescribed fluticasone propionate (0.05%) ointment once daily for the lesions of lichen planus. There was a marked improvement in the lesions of lichen planus after 1 month. Figure 1. Violaceous papules of lichen planus colocalized on vitiligo macules with associated leukotrichia seen on the right leg Figure 2. Histopathology reveals hyperkeratosis, wedge-shaped hypergranulosis, irregular acanthosis with saw toothing of the rete ridges, basal cell liquefaction, and a band-like lymphocytic infiltrate (hematoxylin and eosin, × 40) [source]

Use of Inhaled Corticosteroids and Risk of Fractures

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2001
T. P. Van Staa
Abstract Treatment with systemic corticosteroids is known to increase the risk of fractures but little is known of the fracture risks associated with inhaled corticosteroids. A retrospective cohort study was conducted using a large UK primary care database (the General Practice Research Database [GPRD]). Inhaled corticosteroid users aged 18 years or older were compared with matched control patients and to a group of noncorticosteroid bronchodilator users. Patients with concomitant use of systemic corticosteroids were excluded. The study comprised 170,818 inhaled corticosteroid users, 108,786 bronchodilator users, and 170,818 control patients. The average age was 45.1 years in the inhaled corticosteroid, 49.3 years in the bronchodilator, and 45.2 years in the control groups. In the inhaled corticosteroid cohort, 54.5% were female. The relative rates (RRs) of nonvertebral, hip, and vertebral fractures during inhaled corticosteroid treatment compared with control were 1.15 (95% CI, 1.10,1.20), 1.22 (95% CI, 1.04,1.43), and 1.51 (95% CI, 1.22,1.85), respectively. No differences were found between the inhaled corticosteroid and bronchodilator groups (nonvertebral fracture RR = 1.00; 95% CI, 0.94,1.06). The rates of nonvertebral fractures among users of budesonide (RR = 0.95; 95% CI, 0.85,1.07) and fluticasone propionate (RR = 1.03; 95% CI, 0.71,1.49) were similar to the rate determined for users of beclomethasone dipropionate. We conclude that users of inhaled corticosteroids have an increased risk of fracture, particularly at the hip and spine. However, this excess risk may be related more to the underlying respiratory disease than to inhaled corticosteroid. [source]

Improved synthesis of [18F]fluoromethyl tosylate, a convenient reagent for radiofluoromethylations

JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 8 2005
Timothy R. Neal
Abstract The utility of [18F]fluoromethyl tosylate as an [18F]fluoromethylation reagent has been reexamined. The preparation of this potentially useful compound from the reaction of bis(tosyloxy) methane with 18F- was reported several years ago, but it had not found use as a labeling reagent. When the reported reaction of bis(tosyloxy) methane with 18F- was carried out, [18F]fluoromethyl tosylate was formed along with [18F]tosyl fluoride. The product ratio depended upon reaction conditions, with the yield of [18F]fluoromethyl tosylate usually in the range of 25,40%. Addition of a small amount of water to the reaction mixture resulted in a significant increase in the yield of [18F]fluoromethyl tosylate. Reaction conditions were defined that produced a yield of 71±6% of [18F]fluoromethyl tosylate (decay corrected). The product was conveniently purified by alumina chromatography. Reaction of [18F]fluoromethyl tosylate with the (des-fluoromethyl) fluticasone propionate thioacid precursor produced [18F]fluticasone propionate in improved yield (16%, from fluoride in production-scale runs) over other synthesis methods. Similarly, formation of [18F]choline, [18F]fluoromethionine and N- ([18F]fluoromethyl)spiperone from the reaction of [18F]fluoromethyl tosylate with corresponding precursors was examined. Copyright © 2005 John Wiley & Sons, Ltd. [source]

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

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2004
Anagnostis Valotis
Abstract 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. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1337,1350, 2004 [source]

Time Dependent Effects of Glucocorticoids on Adrenocorticotropin Secretion of Rat Pituitaries Ex-vivo

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2000
R. BRUNS
Different glucocorticoids have been compared with respect to the inhibition of corticotropin-releasing factor (CRF)-mediated adrenocorticotropin (ACTH) secretion from pituitary fragments of the rat. The influence of time of exposure to glucocorticoids and glucocorticoid concentration has been investigated. CRF-stimulated ACTH secretion of perifused rat pituitary fragments was measured by a chemiluminescence immunoassay. ACTH secretion was monitored over three days. Inhibition of CRF-stimulated ACTH secretion by glucocorticoids was quantified by the area under the curve of CRF-stimulated ACTH secretion over baseline. Concentrations needed to inhibit ACTH secretion decreased with the receptor affinities of the glucocorticoids as follows: fluticasone propionate; receptor affinity 1800, concentration 10,8 M; budesonide, 935 and 3,2.5 times 10,8 M; flunisolide, 478 and 5 times 10,7 M; prednisolone, 10 and 10,6 M. CRF-stimulated secretion was inhibited by glucocorticoids after incubation for 1 min at concentrations between 10,8 and 10,6 M. The same absolute quantity of the glucocorticoids produced no inhibition when incubation was prolonged to 50 min or when a lower concentration was used. Immediately after the perifusion stimulation of ACTH secretion was observed. The results suggest the possibility of minimizing the side effects of glucocorticoids by prolonging drug release. [source]

Steroid sparing effects of intranasal corticosteroids in asthma and allergic rhinitis

ALLERGY, Issue 3 2010
A. Nair
To cite this article: Nair A, Vaidyanathan S, Clearie K, Williamson P, Meldrum K, Lipworth BJ. Steroid sparing effects of intranasal corticosteroids in asthma and allergic rhinitis. Allergy 2010; 65: 359,367. Abstract Background:, Treating allergic rhinitis may have a downstream anti-inflammatory effect on the lower airways. We conducted a dose ranging study in asthma and persistent allergic rhinitis to evaluate if intranasal corticosteroids exhibit a sparing effect on the dose of inhaled corticosteroid. Methods:, Twenty five participants were randomized to receive two weeks of 100 ,g/day (Low dose) or 500 ,g/day (High dose) of inhaled fluticasone propionate both with intranasal placebo; or inhaled fluticasone 100 ,g/day with intranasal fluticasone 200 ,g/day (Combined) in a double-blind cross-over fashion. Results:, Low dose fluticasone produced a shift of 1.20 doubling-dilutions (95% CI, 0.63, 1.77); Combined fluticasone, 1.79 doubling-dilutions (95% CI, 0.77, 2.80) and high dose fluticasone, 2.01 doubling-dilutions (95% CI, 1.42, 2.61) in methacholine PC20 from respective baselines. There was a significant difference between high and low doses: 0.82 doubling dilutions (95%CI, 0.12, 1.50) but not between combined and low dose 0.58 doubling dilutions (95% CI, ,0.78, 1.95). Combined treatment alone produced improvements in peak nasal inspiratory flow (P < 0.001), rhinitis quality of life (P = 0.004) and nasal NO (P = 0.01); reduced blood eosinophil count (P = 0.03), and serum eosinophil cationic protein (P = 0.02). All treatments significantly improved tidal NO, FEV1 and asthma quality of life. Conclusions:, High-dose fluticasone was superior to low dose fluticasone for methacholine PC20, demonstrating room for further improvement. Combined treatment was not significantly different from low dose fluticasone and we could not demonstrate a steroid sparing effect on methacholine PC20. Combined treatment alone produced improvements in upper airway outcomes and suppressed systemic inflammation but not adrenal function. [source]

Effects of single-dose fluticasone on exercise-induced asthma in asthmatic children: A pilot study,

PEDIATRIC PULMONOLOGY, Issue 2 2001
B.J. Thio MD
Abstract A single high dose of inhaled corticosteroid (ICS) can increase airway caliber in children with asthma attacks and laryngitis subglottica. Presumably the effect is due to the vasoconstrictive and antiedematous properties of topical steroids. Enlarged vessels have been suggested to play a role in the pathophysiology of exercise-induced bronchial obstruction (EIB). To investigate this, we evaluated the effect of a single high dose of fluticasone propionate (FP) on EIB in asthmatic children. Nine children aged 8,16 years with mild to moderate asthma were included. All children had a history of EIB, which was confirmed by an exercise test. None was taking ICS maintenance therapy. The children inhaled either a single dose of 1 mg FP or placebo on 2 separate days within 7,14 days. After inhalation, airway caliber (FEV1) was assessed for 4 hr before exercise. Then an exercise challenge was performed on a treadmill to assess EIB (% fall FEV1). A significant increase in FEV1 was observed 1 hr after inhalation of FP compared to placebo. Response to exercise was expressed as maximal % fall in FEV1 from baseline (% fall) and as area under the curve (AUC) of the 30-min time/response curve. The % fall FEV1 after exercise and the AUC were significantly reduced when FP was inhaled compared to placebo inhalation (% fall 9.7% vs. 19.2%, respectively, P,=,0.038 and AUC 92.0%,min vs. 205.7%,min, respectively, P,=,0.03). There was considerable individual variability in reduction of EIB, with 5 out of 9 children having a clinically significant response. We conclude that a single high dose of inhaled FP has an acute protective effect on the bronchial response to exercise in a substantial proportion of asthmatic children. Pediatr Pulmonol. 2001; 32:115,121. © 2001 Wiley-Liss, Inc. [source]

Effects of inhaled fluticasone propionate on CTLA-4-positive CD4+CD25+ cells in induced sputum in mild asthmatics

RESPIROLOGY, Issue 7 2008
Tomotaka KAWAYAMA
Background and objective: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) signalling of regulatory T cells regulates mucosal lymphocyte tolerance and differentiation, and may therefore have a beneficial effect in allergic diseases such as asthma. The aim of this study was to evaluate the effects of fluticasone propionate (FP) on CD4+CD25+ T cell co-expression of CTLA-4 in the sputum of mild asthmatic subjects. Methods: Eleven mild, stable asthmatic subjects completed a double-blind, randomized, cross-over, placebo-controlled study to compare the effects of 14 days 200 µg twice daily FP and placebo. Before and after treatment, airway hyperresponsiveness was measured, and sputum was induced for measurements of CTLA-4+CD4+CD25+ cells, eosinophils and levels of IL-10, IL-13 and transforming growth factor (TGF)-, Results: FP treatment increased co-expression of CTLA-4 on sputum CD4+CD25+ cells from a mean (SEM) of 7.9% (1.8) to 12.7% (3.3) after 14 days treatment (P < 0.05) compared with placebo. FP treatment also significantly increased IL-10 levels, reduced per cent sputum eosinophils, and reduced airway hyperresponsiveness (P < 0.05). There was a significant negative correlation between the change in airway hyperresponsiveness and per cent sputum eosinophils (P < 0.01), but no correlation with changes in CTLA-4+CD4+CD25+ cells (P > 0.05). There was no change in the levels of sputum IL-13 or TGF-, Conclusions: The percentage of airway CTLA-4+CD4+CD25+ cells increased after FP treatment, coincident with improvements in airway inflammation and hyperresponsiveness. Whether improved asthma assessments are related to the increase in CTLA-4+CD4+CD25+ cells and thus improved regulation of T-cell tolerance and differentiation will require a larger sample size to determine. The normalization of CTLA-4+CD4+CD25+ cells in asthma may contribute to the management of this disease. [source]

Improvement in health-related quality of life with fluticasone propionate compared with budesonide or beclomethasone dipropionate in adults with severe asthma

RESPIROLOGY, Issue 3 2003
Carolyn RUTHERFORD
Objective: Changes in health-related quality of life (HRQoL) were evaluated in adults with severe asthma following inhaled corticosteroid treatment with high-dose beclomethasone dipropionate or budesonide (BDP/BUD) and compared with fluticasone propionate taken at approximately half the dose of BDP/BUD. Methodology: HRQoL was assessed as part of an open, multicentre, randomized, parallel-group study in Australia evaluating the safety and efficacy of switching to fluticasone propionate (FP) 1000,2000 µg/day (n = 67) compared with remaining on BDP/BUD ,1750 µg/day (n = 66) for 6 months. Patients completed two HRQoL questionnaires, the Asthma Quality of Life Questionnaire (AQLQ) and the Medical Outcomes Study Short Form-36 (SF-36), at baseline and at weeks 12 and 24. A change in AQLQ score of ,0.5 was considered to be clinically meaningful. Results: There were significant improvements in HRQoL with FP on four of the eight dimensions on the SF-36 (i.e. physical functioning, general health, role-emotional, and mental health), while there were no significant improvements in HRQoL in the BDP/BUD group. Overall, patients in the FP group experienced significantly greater improvement (P < 0.001) in AQLQ scores at weeks 12 and 24 compared with the BDP/BUD group. On the individual domains of the AQLQ, there were significant treatment differences (P < 0.01) in favour of FP in three of the four domains (activity limitations [0.92], symptoms [0.73], and emotional function [1.02]). Mean differences between groups for overall score and these three domains were also clinically meaningful. Conclusion: Patients with severe asthma who received FP (at approximately half the dose of BDP/BUD) experienced statistically significant, as well as clinically meaningful, improvements in their HRQoL. [source]

Improved safety with equivalent asthma control in adults with chronic severe asthma on high-dose fluticasone propionate

In vivo comparison of the relative systemic bioavailability of fluticasone propionate from three anti-static spacers and a metered dose inhaler

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2009
Arun Nair
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Conventional spacers help overcome problems with co-ordination and may improve lung deposition and decrease oropharyngeal impaction. , Antistatic spacers eliminate electrostatic charge and may hence improve respirable dose delivery. , The systemic bioavailability of inhaled fluticasone propionate is primarily dependent on delivery by the pulmonary route and hence the performance of antistatic spacers can be evaluated using adrenal suppression as a sensitive surrogate for relative bioavailability to the lung after an inhalation. WHAT THIS STUDY ADDS , This study compares the relative bioavailability to the lung of inhaled fluticasone delivered via conventional pressurized metered dose inhalers (pMDI) and three antistatic spacers (plastic Zerostat-V, plastic Aerochamber Max, and metal Nebuchamber) in patients with asthma. , All three antistatic spacers when compared with pMDI significantly increased the relative bioavailability to the lungs of inhaled fluticasone in terms of relative adrenal suppression, and there were no significant differences between the plastic and metal antistatic spacers. AIMS The systemic bioavailability of inhaled fluticasone propionate (FP) depends primarily on lung absorption and can be quantified by measuring suppression of overnight and early morning urinary cortisol/creatinine (OUCC and EMUCC, respectively). The aim of the study was to determine the relative bioavailability of hydrofluoroalkane (HFA) FP to the lungs via anti-static plastic (Zerostat-V and Aerochamber Max), metal (Nebuchamber) anti-static spacers and metered dose inhaler [Flixotide Evohaler (EH) (pMDI)]. METHODS A randomized, double-blind, double-dummy, four-way crossover design was used. Eighteen mild to moderate asthmatics received single doses of placebo/HFA-FP 2 mg via the 280-ml Zerostat-V (ZS); 250-ml Nebuchamber (NC); 197-ml Aerochamber Max (AC); and pMDI (EH). Measurements of OUCC and EMUCC were made at baseline and 10 h after each dose. RESULTS Significant suppression of OUCC and EMUCC occurred from baseline with all three spacers, but not Evohaler (geometric mean fold suppression, 95% confidence interval): ZS, 2.74 (1.75, 4.30), P < 0.001; NC, 3.31 (1.81, 6.06), P < 0.001; AC, 4.98 (3.39, 7.31), P < 0.001; and for EH this was 1.42 (0.92, 2.21), P= 0.169 (equating to a 64, 70, 80 and 30% fall in OUCC via the ZS, NC, AC and EH devices, respectively). There were significant differences between all three spacers vs. EH. When compared with the Evohaler, the Zerostat V resulted in 48% greater suppression (P= 0.009); the Nebuchamber 57% greater suppression (P= 0.001); and the Aerochamber Max 71% greater suppression of OUCC (P < 0.001). CONCLUSION All three antistatic spacers significantly increased the relative systemic bioavailability of HFA-FP compared with the standard pMDI. [source]

Plasma concentrations of fluticasone propionate and budesonide following inhalation: effect of induced bronchoconstriction

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2007
Kevin J. Mortimer
What is already known about this subject ,,All inhaled corticosteroids are absorbed into the systemic circulation and hence have the potential to cause adverse systemic effects. ,,Plasma drug concentrations following inhalation of 1000 µg fluticasone are considerably lower in people with airflow obstruction than in healthy volunteers but this is not the case for budesonide. What this study adds ,,This is the first study to determine whether changes in airflow obstruction within an individual affect the systemic absorption of inhaled fluticasone and budesonide; ,,Plasma concentrations of fluticasone and, to a lesser extent, those of budesonide were lower when the drugs were inhaled following induced bronchoconstriction; ,,The lower plasma concentrations of corticosteroids seen when the drugs were inhaled following induced bronchoconstriction is likely to reflect variations that will occur with fluctuations in airway caliber in asthma. Aims To determine whether and to what extent bronchoconstriction affects plasma concentrations of fluticasone and budesonide following inhalation. Methods Twenty people with mild asthma inhaled 1000 µg fluticasone (Accuhaler®) plus 800 µg budesonide (Turbohaler®) on two visits. On one occasion, prior to drug inhalation, FEV1 was decreased by at least 25% using inhaled methacholine. Plasma drug concentrations were measured for each drug over 5 h and area under the plasma concentration-time curve (AUC(0,5 h)) compared between visits. Results The mean difference in FEV1 prior to drug inhalation on the 2 days was 33%. AUC(0,5 h) values for fluticasone and budesonide were lower by a median of 60% (IQR 36,75) and 29% (IQR 2,44), respectively, when administered following bronchoconstriction; the reduction was greater for fluticasone than for budesonide, P = 0.007. Conclusions The lower plasma concentrations of fluticasone and, to a lesser extent, budesonide seen when the drugs were inhaled following induced bronchoconstriction, is likely to reflect variations that will occur with fluctuations in airway caliber in asthma. [source]

Wet-wrap treatment using dilutions of tacrolimus ointment and fluticasone propionate cream in human APOC1 (+/+) mice with atopic dermatitis

BRITISH JOURNAL OF DERMATOLOGY, Issue 1 2009
A.P. Oranje
Summary Background, Wet-wrap treatment (WWT) with diluted topical steroids is widely used in atopic dermatitis (AD). Mice with transgenic overexpression of human apolipoprotein C1 (APOC1) in the liver and the skin are not only characterized by hyperlipidaemia and raised IgE levels, but also by pruritic dermatitis and a disturbed skin barrier function, providing a novel in vivo mouse model for AD. Objectives, We investigated an adapted WWT method in the AD model in APOC1 mice in order to establish its efficacy. Methods, The effect of topical 0·1% and 0·03% tacrolimus ointment, tacrolimus base ointment, different dilutions of 0·05% fluticasone propionate (FP) cream and emollient on the development of dermatitis in APOC1 mice was investigated. WWT was performed with 0·03% tacrolimus ointment or 0·017% FP cream. Results, AD in APOC1 mice responded to topical treatment with tacrolimus or FP. In contrast to tacrolimus treatment, FP treatment was associated with loss of body weight. WWT reinforced several therapeutic aspects, notably improvements in transepidermal water loss and in epidermal thickness. WWT using tacrolimus 0·03% ointment was more effective than WWT using FP 0·017% cream. Conclusions, AD in APOC1 mice responds to treatment with (diluted) tacrolimus or FP; treatment with FP cream, but not tacrolimus ointment, was associated with weight loss. In this study, the adapted WWT using tacrolimus or FP in mice had a limited improving effect as compared with open application of tacrolimus or FP. [source]

Intermittent dosing of fluticasone propionate cream for reducing the risk of relapse in atopic dermatitis patients

BRITISH JOURNAL OF DERMATOLOGY, Issue 3 2002
J. Hanifin
Summary Background One of the most troublesome features of atopic dermatitis (AD) is its chronic relapsing nature, and there is a lack of published evidence on the best treatment strategy for long-term management of the disease. Objectives To compare an intermittent dosing regimen of fluticasone propionate (FP) cream 0·05% (twice per week) with its vehicle base in reducing the risk of relapse when added to regular daily emollient in adult and paediatric subjects with stabilized AD. Methods Subjects (aged 3 months to 65 years) with moderate or severe AD were enrolled into an open-label Stabilization Phase of up to 4 weeks on daily emollients plus FP twice daily. Those subjects who achieved ,treatment success' (Global Assessment Score ,,2, erythema, pruritus, and papulation/induration/oedema scores ,,1) entered the double-blind Maintenance Phase. They continued with regular emollients and were randomized at a 2 : 1 ratio to either intermittent FP or vehicle, once daily 4 days per week for 4 weeks followed by once daily 2 days per week for 16 weeks. Subjects who relapsed on intermittent FP were discontinued from the study. Those who did not relapse continued for an additional 24 weeks on intermittent dosing for safety monitoring. Results A total of 372 (247 paediatric, 125 adult) subjects were enrolled into the Stabilization Phase. Of these, 348 (231 children, 117 adults) were randomized into the Maintenance Phase. Analysis of the primary efficacy parameter showed that subjects receiving intermittent FP cream (twice per week), in addition to regular daily emollients in the Maintenance Phase, were 7·7 times less likely to have an AD relapse than subjects receiving intermittent vehicle cream/emollients [Mantel,Haenszel (MH) estimate of the odds ratio, 95% confidence interval (CI) 4·6, 12·8; P < 0·001]. Paediatric subjects were 8·1 times less likely to have an AD relapse (95% CI 4·3, 15·2; P < 0·001) and adult subjects were 7·0 times less likely to have an AD relapse (95% CI 3·0, 16·7; P < 0·001). For subjects receiving intermittent FP cream/emollient, the median time to relapse could not be estimated as the majority remained controlled at 20 weeks. For those receiving intermittent vehicle/emollient, the median time to relapse was 4·7 weeks. For paediatric and adult groups, this was 5·1 and 4·1 weeks, respectively. Median exposure to FP for all subjects was 337 days. There was only one study drug-related adverse event (acne) and there were no reports of skin thinning or atrophy associated with the use of FP cream in paediatric or adult subjects. Conclusions In paediatric and adult subjects, once stabilized with regular FP treatment, the risk of relapse of AD can be significantly reduced by extended intermittent dosing with FP cream in addition to regular emollient therapy. [source]

Repeatability of the low-dose ACTH test in asthmatic children on inhaled corticosteroids

ACTA PAEDIATRICA, Issue 12 2009
Atul Gupta
Abstract Aim:, To assess the repeatability of low-dose Synacthen test (LDST) in asthmatic children receiving high-dose fluticasone propionate (FP). Methods:, Low-dose Synacthen test was performed on 18 children with stable chronic asthma treated with FP at a constant daily dose of ,500 ,g and repeated 1 month later. Repeatability was assessed using the Kappa statistic for categorical variables. Results:, Fifteen patients had consistent results (either two normal or two abnormal responses) and three patients had inconsistent results (one normal and one abnormal response). The Kappa statistic was 0.56 indicating fair to good agreement between the tests. Conclusion:, The results of adrenal function testing in patients on inhaled steroids can have major implications for patient management, making it important to use a test with excellent repeatability. The LDST conducted using our protocol does not fulfil this criterion. [source]

The topical glucocorticoids beclomethasone dipropionate and fluticasone propionate inhibit human T-cell allergen-induced production of IL-5, IL-3 and GM-CSF mRNA and protein

CLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2001
N. Powell
T-cell production of eosinophil-active cytokines (IL-5, IL-3, GM-CSF) is thought to be fundamental to asthma pathogenesis. Inhaled aeroallergens may be one important stimulus for T-cell cytokine production in asthma. To compare the potency and efficacy of the topical anti-asthma glucocorticoids beclomethasone dipropionate (BDP) and fluticasone propionate (FP) in inhibiting allergen-driven peripheral blood T-cell proliferation and production of IL-3, IL-5 and GM-CSF mRNA and protein. Peripheral blood mononuclear cells from six atopic asthmatics sensitized to house dust mite (HDM) were cultured in the presence of HDM and serial dilutions of BDP or FP in vitro. Cellular proliferation (7 days) and culture supernatant cytokine concentrations (6 days) were measured by uptake of tritiated thymidine and ELISA, respectively. Cytokine mRNA expression (24 h) was measured in three subjects using a quantitative PCR technique. Both BDP and FP inhibited allergen-induced T-cell proliferation, expression of IL-3, IL-5 and GM-CSF mRNA, and secretion of the corresponding proteins in a concentration-dependent fashion. FP was considerably more potent, but not more efficacious, in exerting these actions. Both BDP and FP have the potential markedly to inhibit allergen-induced T-cell production of asthma-relevant cytokines. This activity is effected at the level of T-cell proliferation and cytokine gene transcription. These properties may be key features of the anti-asthma activity of these drugs. The greater potency of FP in vitro may be responsible for its greater clinical potency. [source]