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PubMed2006

Comparison between compliance of fluticasone propionate diskhaler and of fluticasone propionate diskus in adult bronchial asthma patients.

BACKGROUND AND OBJECTIVES: Because inhaled corticosteroids (ICS) play a central role in the management of asthma, new drug delivery systems for fluticasone propionate, Diskhaler (FPdh) and Diskus (FPdk), were developed. However, few studies have focused on compliance with these drug delivery systems, which can influence drug efficacy. Hence, we compared compliance with FPdk versus that with FPdh. METHODS: Data were obtained from a survey of pharmacists dispensing anti-asthmatic drugs to adult asthma patients who visited participating pharmacies between October 2002 and November 2003. Patients were limited to regular users of FPdh or FPdk whose medication had not been changed for >6 months before the survey. Compliance and daily administration frequency of ICS were evaluated on the basis of pharmaceutical records. Data on asthma status and various other factors affecting ICS compliance were obtained by questionnaire. RESULTS: Data were acquired on 337 patients. There were no significant differences in gender, age, and duration between the FPdk and FPdh groups. Although FPdk compliance was significantly higher than that of FPdh, conversely there was no significant difference in daily dose and administration frequency between the 2 groups. Furthermore, there was no significant difference in the rate of concomitant drug and in various influencing factors associated with drug compliance. Regarding compliance of concomitant drug, that of oral sustained-released theophylline was significantly lower in FPdk versus FPdh users. CONCLUSION: In the area of drug compliance, FPdk is superior to FPdh. Although the reason for this is unclear, it is probably due to the characteristics of FPdk itself.

Administration, Inhalation↗
PubMed2004

Cost effectiveness of fluticasone propionate plus salmeterol versus fluticasone propionate plus montelukast in the treatment of persistent asthma.

BACKGROUND: Asthma is a chronic disease, the two main components of which are inflammation and bronchoconstriction. Fluticasone propionate (FP) and salmeterol, a strategy that treats both main components of asthma, has been recently compared with FP plus montelukast in a randomised clinical trial. The present study reports economic evaluation of these two strategies. OBJECTIVE: To determine the relative cost effectiveness when persistent asthma is treated with FP/salmeterol 100/50 microg twice daily administered via a single Diskus inhaler device versus treatment with FP 100 microg twice daily via a Diskus inhaler plus oral montelukast 10mg once daily. STUDY DESIGN: A cost-effectiveness analysis was performed by applying cost unit data to resource utilisation data collected prospectively during a US randomised, double-blind, 12-week trial of FP/salmeterol (n = 222) versus FP + montelukast (n = 225). Patients were > or =15 years of age and were symptomatic despite inhaled corticosteroid (ICS) therapy. PATIENTS AND METHODS: Efficacy measurements in this analysis included improvement in forced expiratory volume in 1 second (FEV(1)) and symptom-free days. Direct costs included those related to study drugs, emergency room department visits, unscheduled physician visits, treatment of drug-related adverse events (oral candidiasis), and rescue medication (salbutamol [albuterol]). The study assumed a US third-party payer's perspective with costs in 2001 US dollars. RESULTS: Treatment with FP/salmeterol resulted in a significantly higher proportion (p < 0.001) of patients who achieved a > or =12% increase in FEV(1) than treatment with FP + montelukast (54% [95% CI 47%, 61%] vs 32% [95% CI 26%, 38%]). Lower daily costs and greater efficacy of FP/salmeterol resulted in a cost-effectiveness ratio of US6.77 dollars (95% CI US5.99 dollars, US7.66 dollars) per successfully treated patient in the FP/salmeterol group compared with US14.59 dollars (95% CI US12.12 dollars, US17.77 dollars) for FP + montelukast. In addition, FP/salmeterol achieved similar efficacy in terms of symptom-free days compared with FP + montelukast (31% [95% CI 26%, 35%] vs 27% [95% CI 23%, 32%]), but at a significantly lower daily per-patient cost (US3.64 dollars [95% CI US3.60, US3.68 dollars] vs US4.64 dollars [95% CI US4.56 dollars, US4.73 dollars]). Sensitivity analyses demonstrated the stability of the results over a range of assumptions. CONCLUSION: From a US third-party payer's perspective, these findings suggest that treating the two main components of asthma (inflammation and bronchoconstriction) with FP/salmeterol may not only be a more cost-effective strategy but may actually lead to cost savings compared with the addition of montelukast to low-dose FP in patients with persistent asthma. The results were found to be robust over a range of assumptions.

Acetates↗
PubMedDate not supplied

Efficacy of fluticasone propionate compared with beclomethasone dipropionate in bronchial asthma: improvement in compliance and symptoms by fluticasone.

Recent studies have shown that fluticasone propionate (FP) was more effective than beclomethasone dipropionate (BDP) inhalation even at a dose reduced by twofold or more in the treatment of bronchial asthma. Here, we further compared the effectiveness of FP and BDP, including rates of drug compliance. Forty-two symptomatic patients were treated by BDP (1000 +/- 345; mean +/- SD; microgram/day) for 8 weeks, followed by FP at one-half the respective dose, and peak expiratory flow and forced expiratory volume in 1 second were investigated. In addition, the patients were asked about drug compliance and factors related to compliance (expressed using a visual analogue scale). Significant increases of peak expiratory flow (from 316 +/- 96 L/minute to 345 +/- 86 L/minute) and forced expiratory volume in 1 second (from 1.7 +/- 0.5 L to 1.9 +/- 0.4 L) were found. Furthermore, significantly higher scores were obtained for compliance and various factors related to compliance. These data indicate that FP is more effective than a twofold higher dosage of BDP and that better compliance with the use of FP, probably because of improved various factors associated with FP compliance, contributes to FP efficacy.

Adult↗
PubMed2004

[Effectiveness and safety of fluticasone propionate in therapy of children suffering from asthma. Part II. Safety aspects of therapy with fluticasone propionate in asthmatic children].

Inhaled administration of glucocorticoid doesn't mean lack of systemic effects of drug. Bioavailability of steroid depends on oral absorption and absorption from respiratory system. In case of fluticasone propionate (FP) swallowed dose can be neglected because almost total (>99%) inactivation in liver during first pass. In second part of paper the most important safety parameters of therapy with FP are discussed, it means; influence on hypothalamic-pituitary-adrenal axis, growth and bone metabolism. Interpretation of potential side effects should differentiate between abnormal value of laboratory test and clinically important symptoms. Adrenal suppression depends on dose of FP and was found even after low dose (about 200 microg per day), but clinical value of this findings is unknown. Prolonged administration of high doses can suppress hypothalamic-pituitary-adrenal axis; exceptionally, it can induce adrenal insufficiency. Recommended doses of FP given 1 to 2 years doesn't cause growth retardation. Long term studies on influence of drug on final height are needed. FP as other inhaled corticosteroids, may transiently alter bone metabolism. Till now there are no evidences that this drug, when prescribed appropriately in standard doses for asthma control, may decrease the bone mineral density or induce osteoporosis and may increase the risk of bone fractures in asthmatic children. Effective asthma control achieved with FP therapy permits normal activity and development of asthmatic children which prevails over exceptionally noticed side effects.

Administration, Inhalation↗
PubMed2006

[Cost-effectiveness of fluticasone propionate for asthma episodes in Japanese patients with asthma--Fluticasone Investigation of Asthma Episode (FINE) study].

BACKGROUND: To discuss and estimate the economic benefits gained by fluticasone propionate (FP) for patients with asthma over hospitalization, emergency room visit, unscheduled visit, and absence (representative by asthma-related episode). METHOD: Asthma-related episodes in pre and post 6 months of FP use were derived from a survey of FP on asthma-related episodes (FINE study). Medical cost was evaluated by macro-cost estimate and productivity loss by human capital approach. RESULTS: Discussion of asthma-related episodes in-between before and after the use of FP in eight hundred ninety-eight valuable subjects revealed that FP use significantly reduced asthma-related episodic costs of approximately 120,000 yen (p<0.001), whereas total drug acquisition costs for being newly consumed FP, leukotriene receptor antagonists, inhaled short-acting beta2 agonists, etc were significantly increased by approximately 16,000 yen. Moreover, while significantly avoiding productivity loss of approximately about 35,000 yen it totally provided cost-savings of about 70,000 yen at the patients' viewpoint. When sensitivity analyses were performed by adjusting the confounding factors using analysis of covariance, the aforementioned base case results might be persistent. For safety of FP, some adverse events related to the use of FP were identified of about 2.0%, and there were not any serious ones at all. CONCLUSION: The economic evaluation of FP demonstrated that it is sufficient, whereas an acquisition cost was increased. Use of FP economically impacts on Japanese society and patients.

Adult↗
PubMed2001

Pharmacokinetics and systemic activity of fluticasone via Diskus and pMDI, and of budesonide via Turbuhaler.

AIMS: To determine the basal pharmacokinetics, lung uptake and plasma cortisol suppression for two commonly prescribed inhaled corticosteroids. METHODS: Twenty-one subjects (13 healthy and 8 mild asthmatic patients) received fluticasone propionate via a chlorofluorocarbon-propelled pressurized metered-dose inhaler (pMDI) (healthy subjects only) and Diskus and budesonide via Turbuhaler, 1000 microg twice daily for 7 days. Intravenous doses (200 microg) of both compounds were used as references. Plasma concentrations of fluticasone and budesonide were determined during 48 h by liquid chromatography plus tandem mass spectrometry (LC-MS-MS). Plasma concentrations of cortisol were determined by LC-MS every second hour for 24 h at baseline, and following each treatment. RESULTS: The volume of distribution was found to be larger and the elimination half-life and mean absorption time longer for fluticasone than for budesonide. The systemic availability of budesonide via Turbuhaler (39%) was significantly higher than that of fluticasone via Diskus (13%) (ratio 3.0 [2.5, 3.6] with 95% confidence interval [CI]), and via pMDI (21%) (ratio 1.8 [1.3, 2.3]). In addition, at steady state the systemic availability of fluticasone via pMDI was significantly higher than via Diskus (ratio 1.6 [1.1, 2.2]). The lung deposition of budesonide via Turbuhaler was 2.2-fold [1.7, 2.9] higher than that of fluticasone pMDI and 3.4-fold [2.8, 4.0] higher than that of fluticasone Diskus. In addition, the lung deposition of fluticasone via pMDI was 1.5-fold [1.1, 2.9] higher than that via the Diskus inhaler. Plasma cortisol (24 h) was significantly reduced vs baseline for all three treatments. The cortisol concentration vs baseline was 12% for fluticasone pMDI, which was significantly lower (ratio 0.32 [0.24, 0.42]) than that for fluticasone Diskus (39%), and for budesonide Turbuhaler (46%) (ratio 0.27 [0.21, 0.37]). The plasma cortisol concentration did not differ significantly between treatments with fluticasone Diskus and budesonide Turbuhaler (ratio 0.87 [0.65; 1.15]). CONCLUSIONS: Budesonide and fluticasone differ in their pharmacokinetic properties in that although clearance is the same, the rate of uptake and elimination is slower for fluticasone. Despite a significantly higher pulmonary availability of budesonide via Turbuhaler, the plasma cortisol suppression is less than that of fluticasone via pMDI and similar to that of fluticasone via Diskus. There is no indication of any difference between healthy subjects and mild asthmatic patients in the pharmacokinetics and plasma cortisol suppression of fluticasone and budesonide.

Administration, Inhalation↗
PubMed1999

Evaluation of the buccal component of systemic absorption with inhaled fluticasone propionate.

BACKGROUND: Inhaled corticosteroids have dose related systemic effects determined by oral (swallowed or oropharyngeal absorption) and lung bioavailability. A study was undertaken to evaluate the significance of oropharyngeal absorption for fluticasone propionate. METHODS: Sixteen healthy volunteers of mean age 29.3 years were studied using an open randomised, placebo controlled, four way crossover design. Treatments were: (a) fluticasone metered dose inhaler (pMDI) 250 microg, 8 puffs; (b) fluticasone pMDI 250 microg, 8 puffs + mouth rinsing/gargling (water); (c) fluticasone pMDI 250 microg, 8 puffs + mouth rinsing/gargling (charcoal); and (d) placebo pMDI, 8 puffs + mouth rinsing/gargling (water). Overnight (ONUC) and early morning (EMUC) urinary cortisol/creatinine ratios and 8 am serum cortisol (SC) levels were measured. RESULTS: Significant (p<0. 05) suppression of ONUC, EMUC, and SC occurred with each active treatment compared with placebo. The mean values (95% CI for difference from placebo) were: (a) ONUC (nmol/mmol): fluticasone (2. 8, 95% CI 3.6 to 7.9), fluticasone + water (3.1, 95% CI 3.3 to 7.7), fluticasone + charcoal (2.3, 95% CI 4.1 to 8.5); placebo (8.6); (b) EMUC (nmol/mmol): fluticasone (5.6, 95% CI 8.4 to 24.5), fluticasone + water (7.6, 95% CI 6.6 to 22.4); fluticasone + charcoal (5.6, 95% CI 8.7 to 24.5); placebo (22.1). There were no significant differences between active treatments. The numbers of subjects with an overnight urinary cortisol of <20 nmol/10 hours were 0 (placebo), 11 (fluticasone), 12 (fluticasone + water), and 13 (fluticasone + charcoal). CONCLUSIONS: Oropharyngeal absorption of fluticasone does not significantly contribute to its overall systemic bioactivity as assessed by sensitive measures of adrenal suppression. In view of almost complete hepatic first pass inactivation with fluticasone, there is no rationale to employ mouth rinsing to reduce its systemic effects although it may be of value for reducing oral candidiasis.

Absorption↗
PubMed1999

Inhaled fluticasone propionate: a review of its therapeutic efficacy at dosages < or = 500 microg/day in adults and adolescents with mild to moderate asthma.

UNLABELLED: Fluticasone propionate is a corticosteroid with comparatively high receptor affinity and topical activity. Inhaled fluticasone propionate < or =500 microg/day provided effective corticosteroid maintenance treatment in patients with mild to moderate asthma in randomised, controlled clinical studies of 4 to 24 weeks in duration. Dosages of 50 to 250 microg twice daily produced consistent improvement in spirometric measures of lung function, reduced the frequency of as-needed beta2-agonist bronchodilator use, asthma symptom scores and night-time wakenings, and prevented asthma exacerbations compared with placebo. Fluticasone propionate < or =250 microg twice daily provided significantly greater improvements in lung function than nedocromil 4 mg 4 times daily, theophylline (5 to 15 mg/L) or zafirlukast 20 mg twice daily. Health-related quality of life improved significantly with fluticasone propionate 88 microg twice daily, but not zafirlukast 20 mg twice daily or placebo. In comparative trials in which fluticasone propionate was given at half the dosage of beclomethasone dipropionate, budesonide or flunisolide, fluticasone propionate < or =250 microg twice daily produced equivalent or greater improvement in spirometric parameters and equivalent reductions in the use of as-needed beta2-agonists than beclomethasone dipropionate, budesonide or flunisolide. Fluticasone propionate 250 microg twice daily was generally more effective than triamcinolone acetonide 200 microg 4 times daily in two 24-week trials. The combination of inhaled fluticasone propionate < or =250 plus salmeterol < or =50 microg twice daily allowed for the use of lower dosages of the inhaled corticosteroid. The incidence of adverse events in patients receiving inhaled fluticasone propionate 50 to 250 microg twice daily was similar to that in beclomethasone dipropionate 168 to 500 microg twice daily and budesonide 100 to 600 microg twice daily recipients and greater than that in recipients of triamcinolone acetonide 200 microg 4 times daily in comparative trials. The incidence of oral candidiasis was < or =8% in patients treated with fluticasone propionate < or =250 microg twice daily or other agents. There was no evidence of clinically significant hypothalamo-pituitary-adrenal (HPA) axis suppression with fluticasone propionate < or =250 microg twice daily in comparative trials. CONCLUSIONS: Inhaled fluticasone propionate < or =500 microg/day is an effective antiinflammatory therapy for mild to moderate asthma in adolescents and adults. The drug is more effective than nedocromil, theophylline or zafirlukast and is at least as effective as other inhaled corticosteroids administered at twice the fluticasone propionate dosage. The addition of inhaled salmeterol allows the use of lower maintenance dosages of fluticasone propionate. The drug is well tolerated and there is no evidence of a clinically significant effect of this dosage on HPA axis function. Hence, fluticasone propionate < or =500 microg/day is a particularly suitable agent for patients with mild to moderate asthma.

Administration, Inhalation↗
PubMedDate not supplied

The efficacy of fluticasone propionate aqueous nasal spray for allergic rhinitis and its relationship to topical effects.

Fluticasone propionate aqueous nasal spray is an intranasal corticosteroid for the treatment of patients with allergic rhinitis. This double-masked, double-dummy, parallel-group study was conducted to confirm that the efficacy of fluticasone propionate nasal spray is attributable to topical rather than systemic effects. A total of 304 patients with documented seasonal allergic rhinitis were randomly assigned to receive fluticasone propionate nasal spray 200 micrograms once daily (n = 77), oral fluticasone propionate 5 mg once daily (n = 73), oral fluticasone propionate 10 mg once daily (n = 77), or placebo (n = 77) for 14 days. Plasma fluticasone propionate concentrations were determined at baseline and after 14 days of treatment (day 15). Nasal symptoms were recorded daily by patients and assessed weekly by clinicians. On day 15, more patients in the oral fluticasone propionate 5-mg or 10-mg groups, compared with patients in the fluticasone propionate nasal spray group or the placebo group, had detectable plasma fluticasone propionate concentrations, and mean concentrations were higher in the oral fluticasone propionate groups. Both clinician- and patient-rated total and individual nasal symptom scores for obstruction, rhinorrhea, sneezing, and itching were significantly lower in the fluticasone propionate nasal spray group compared with either of the oral fluticasone propionate groups or the placebo group. With few exceptions, oral fluticasone propionate (5 mg or 10 mg) was not significantly different from placebo on any measures of efficacy. These findings indicate that the efficacy of fluticasone propionate nasal spray (200 micrograms once daily) in the treatment of allergic rhinitis results from direct topical effects rather than from indirect effects after systemic absorption.

Absorption↗
PubMed2005

The safety of twice-daily treatment with fluticasone propionate and salmeterol in pediatric patients with persistent asthma.

BACKGROUND: For children older than 5 years with asthma who remain symptomatic despite inhaled corticosteroid (ICS) therapy, the preferred treatment is to add an inhaled long-acting beta2-agonist vs increasing the ICS dose. OBJECTIVE: To compare the safety of twice-daily treatment with inhaled fluticasone propionate plus the inhaled long-acting beta2-agonist salmeterol with that of fluticasone propionate used alone in children aged 4 to 11 years with persistent asthma. METHODS: A randomized, multicenter, double-blind, active-controlled, parallel-group study in 203 children with persistent asthma who were symptomatic during ICS therapy. Patients received fluticasone propionate-salmeterol (100/50 microg) or fluticasone propionate (100 microg) alone twice daily for 12 weeks. RESULTS: The safety profile of fluticasone propionate-salmeterol was similar to that of fluticasone propionate alone. The overall incidence of adverse events was 59% for fluticasone propionate-salmeterol and 57% for fluticasone propionate. Both treatments were well tolerated. Two patients receiving fluticasone propionate-salmeterol and 5 receiving fluticasone propionate withdrew from the study because of worsening asthma. Changes in heart rate, blood pressure, and laboratory variables were infrequent and were similar between treatments. No patients had clinically significant abnormal electrocardiographic findings during treatment. Geometric mean 24-hour urinary cortisol excretion at baseline and after 12 weeks of treatment was comparable within and between groups; no patient in either group had abnormally low 24-hour urinary cortisol excretion after 12 weeks of treatment. The incidence of withdrawals due to asthma exacerbations was 2% in the fluticasone propionate-salmeterol group and 5% in the fluticasone propionate group. CONCLUSIONS: In pediatric patients with persistent asthma, fluticasone propionate-salmeterol twice daily was well tolerated, with a safety profile similar to that of fluticasone propionate used alone.

Adrenergic beta-Agonists↗
PubMed1996

Comparative adrenal suppression with inhaled budesonide and fluticasone propionate in adult asthmatic patients.

BACKGROUND: A study was performed to compare the adrenal suppression caused by inhaled fluticasone propionate and budesonide on a microgram equivalent basis, each given by metered dose inhaler to asthmatic patients. METHODS: Twelve asthmatic patients of mean age 29.9 years, with a forced expiratory volume in one second (FEV1) 92.9% predicted and forced expiratory flow 25-75% (FEF25-75) 69.5% predicted, on less than or equal to 400 micrograms/day inhaled corticosteroid, were studied in a double blind placebo controlled crossover design comparing single doses of inhaled budesonide 400, 1000, 1600, 2000 micrograms and fluticasone propionate 500, 1000, 1500, 2000 micrograms. Doses were administered at 22.00 hours by metered dose inhaler with mouth rinsing and measurements were made in the laboratory 10 hours later. RESULTS: Serum cortisol levels compared with placebo (mean 325.2 nmol/l) were suppressed by fluticasone at doses of 1500 micrograms (211.6 nmol/l) and 2000 micrograms (112.3 nmol/l) and by budesonide at 2000 micrograms (243.4 nmol/l). Fluticasone propionate 2000 micrograms produced lower absolute serum cortisol levels than budesonide 2000 micrograms (95% CI for difference 42.9 to 219.2). The dose ratio (geometric mean) for the relative potency was 2.89 fold (95% CI 1.19 to 7.07). In terms of percentage suppression versus placebo, fluticasone propionate also produced greater effects (means and 95% CI for difference): budesonide 1600 micrograms (16.0) versus fluticasone propionate 1500 micrograms (40.9) (95% CI -0.6 to 50.6), budesonide 2000 micrograms (26.0) versus fluticasone 2000 micrograms (65.2) (95% CI 10.5 to 67.8). Individual serum cortisol levels at the two highest doses showed 15 of 24 patients below the normal limit of the reference range (150 nmol/l) for fluticasone and five of 24 for budesonide. Fluticasone propionate also caused greater ACTH suppression than budesonide (as % versus placebo): budesonide 1600 micrograms (12.0) versus fluticasone propionate 1500 micrograms (31.9) (95% CI 7.6 to 32.1), budesonide 2000 micrograms (13.5) versus fluticasone propionate 2000 micrograms (44.4) (95% CI 13.2 to 48.7). For overnight 10 hour urinary cortisol (nmol/10 hours) there was a difference between the lowest doses of the two drugs: budesonide 400 micrograms (37.2) versus fluticasone propionate 500 micrograms (19.9) (95% CI 6.9 to 27.8). CONCLUSIONS: Like budesonide the systemic bioactivity of fluticasone propionate is mainly due to lung vascular absorption. Fluticasone propionate exhibited at least twofold greater adrenal suppression than budesonide on a microgram equivalent basis in asthmatic patients.

Administration, Topical↗
PubMedDate not supplied

Salmeterol and fluticasone propionate given as a combination. Lack of systemic pharmacodynamic and pharmacokinetic interactions.

OBJECTIVE: To investigate the potential for systemic pharmacodynamic and pharmacokinetic interactions between inhaled salmeterol and fluticasone propionate when repeat doses of the two drugs are given in combination to healthy subjects. METHODS: Twenty-eight healthy subjects received salmeterol 100 microg, salmeterol 100 microg/fluticasone propionate 500 microg and fluticasone propionate 500 microg via a Diskus dry powder inhaler twice daily for 11 days according to a randomised, double-blind, placebo-controlled, crossover design. Subjects in the placebo group also received a single dose of salmeterol 100 microg on the morning of day 10. On day 10, the systemic effects of salmeterol [on pulse rate, blood pressure, corrected QT (QTc) interval and serum potassium and glucose levels] and fluticasone propionate (on 24-h urinary cortisol and morning plasma cortisol levels) were assessed. Maximal number and affinity of lymphocyte beta2-adrenoceptors and beta2-adrenoceptor polymorphism at loci 16 and 27 were also determined. Plasma pharmacokinetics of salmeterol and fluticasone propionate were determined after the morning dose on day 10. Dosing continued on the evening of day 10 and on day 11, and on day 12 the effect of repeat-dose treatment with salmeterol and salmeterol/fluticasone propionate on the systemic effects of cumulative doses of inhaled salbutamol (up to a total dosage of 3,200 microg) was evaluated. RESULTS: All treatments were safe and well tolerated. With the exception of a higher pulse rate after repeat administration of salmeterol [66.2 beats per minute (bpm) versus 63.6 bpm], there were no significant differences between the single-dose and repeat-dose salmeterol groups. The systemic pharmacodynamic effects of inhaled salmeterol were not affected by the co-administration of fluticasone propionate. Eleven days of treatment with salmeterol induced tachyphylaxis to the systemic effects of cumulative doses of salbutamol; however, co-administration of fluticasone propionate did not affect the response to salbutamol. Fluticasone propionate reduced 24-h urinary cortisol excretion (22.4 microg compared with 48.6 microg with placebo), but this was unaffected by the co-administration of salmeterol. Morning plasma cortisol levels were not reduced compared with placebo. There was no significant treatment effect on lymphocyte beta2-adrenoceptors and no correlation of beta2-adrenoceptor polymorphism at loci 16 and 27 with the development of tachyphylaxis. Salmeterol plasma concentrations were measurable only during the first half-hour after dosing. Co-administration of fluticasone propionate did not affect the peak plasma concentration (Cmax) of salmeterol. For fluticasone propionate, there were no statistically significant differences between salmeterol/fluticasone propionate and fluticasone propionate with respect to Cmax, plasma concentration at the end of the dosing interval (Ct), terminal elimination half-life (t1/2) or time to Cmax (tmax). The area under the concentration-time curve within a dosing interval (AUCt) for fluticasone propionate after inhalation of salmeterol/fluticasone propionate was statistically significantly higher (about 8%) than after inhalation of fluticasone propionate alone (P=0.0135). However, the 90% confidence intervals (CIs) for the AUCt and Cmax ratios for the two treatments were within the accepted limits for bioequivalence (1.03, 1.13 and 0.97, 1.12, respectively). CONCLUSION: These results in healthy subjects indicate that there is no systemic pharmacodynamic or pharmacokinetic interaction between inhaled salmeterol and fluticasone propionate when given in combination.

Administration, Inhalation↗
PubMed2005

Fluticasone propionate plasma concentration and systemic effect: effect of delivery device and duration of administration.

BACKGROUND: Inhaled corticosteroids are the preferred therapy in persistent asthma. Dry powder inhalers (DPIs) generate a larger particle size compared with metered-dose inhalers (MDIs), which affects pulmonary deposition, bioavailability, and subsequent systemic effects of fluticasone propionate (fluticasone). OBJECTIVE: To examine the relationship of fluticasone pharmacokinetics and cortisol suppression for 2 fluticasone formulations (DPI and MDI) administered in adults over 1-week and 6-week treatment periods. METHODS: Two previous studies conducted in adults by the Asthma Clinical Research Network examined relative efficacy and systemic effect of fluticasone from MDI and DPI. Sample sets (n=33) were analyzed for fluticasone after administration of 352 microg from the MDI, and 400 microg from the DPI formulation, twice daily, after a 1-week treatment period. The second study's sample sets (n=9) were analyzed for fluticasone after 6 weeks therapy at 352 microg twice daily from the MDI formulation, allowing achievement of steady state. RESULTS: ANOVA revealed a significant trend of increasing fluticasone area under the curve from 0 to time t (AUC(0-->t)) when comparing DPI with MDI for 1 week with MDI for 6 weeks (P<.0001). Similarly, ANOVA revealed increasing cortisol suppression between these groups (P=.007). Linear regression demonstrated that increasing fluticasone AUC(0-->t) was significantly correlated with cortisol suppression (P<.0001; r(2)=0.41). MDI for 6 weeks showed increasing fluticasone AUC (P=.0008, t test) compared with MDI for 1 week, suggesting accumulation. CONCLUSION: Fluticasone plasma concentrations are significantly greater after MDI compared with DPI, and cortisol suppression is associated with fluticasone plasma concentrations. Accumulation of fluticasone concentrations suggests that time to steady state exceeds 1 week of treatment with MDI.

Administration, Inhalation↗
PubMed1993

Comparison of the efficacy and safety of inhaled fluticasone propionate 200 micrograms/day with inhaled beclomethasone dipropionate 400 micrograms/day in mild and moderate asthma.

This study was designed to compare the efficacy and safety of a new inhaled corticosteroid, fluticasone propionate at a total daily dose of 200 micrograms, with beclomethasone dipropionate 400 micrograms/day in childhood asthma. A total of 398 asthmatic children (aged 4-19 years) were randomised to receive either fluticasone propionate 200 micrograms daily or beclomethasone dipropionate 400 micrograms daily for six weeks inhaled via a spacer device from a metered dose inhaler. During the study the patients recorded morning and evening peak expiratory flow rate (PEFR), symptom scores, and use of beta 2 agonist rescue medication. In addition, clinic visit PEFR and forced expiratory volume in one second were measured. Safety was assessed by recording all adverse events and by performing routine biochemistry and haematology screens including plasma cortisol concentration before and after treatment. For the purposes of analysis the diary card data were grouped into three periods: week 3 (days 15-21), week 6 (days 36-42), and weeks 1-6 (days 1-42). The results showed no significant difference between treatments on most efficacy parameters. However, there were significant differences in changes from baseline in favour of fluticasone propionate for % predicted morning PEFR both at week 3 (fluticasone propionate 6.1%, beclomethasone dipropionate 3.9%) and at week 6 (fluticasone propionate 8.3%, beclomethasone dipropionate 5. 9%) and % predicted evening PEFR at week 6 (fluticasone propionate 7.3%, beclomethasone dipropionate 4.9% and over weeks 1-6 (fluticasone propionate 5.5%, beclomethasone dipropionate 3.6%. Comparison between groups showed that the group receiving fluticasone propionate had a lower % of days with symptom-free exercise at week 6 (fluticasone propionate 87%, beclomethasone dipropionate 81%) and % days without rescue medication at week 6 (fluticasone propionate 87%, beclomethasone dipropionate 80%) and over weeks 1-6 (fluticasone propionate 80%, beclomethasone dipropionate 73%). Except for a higher incidence of sore throat in the fluticasone propionate group, the two treatments did not differ with regard to safety. There was no evidence of adrenal suppression with either treatment. In conclusion, fluticasone propionate 200 microgram daily ws at least as effective and as well tolerated as beclomethasone dipropionate 400 microgram daily in childhood asthma.

Administration, Inhalation↗
PubMed1996

Fluticasone propionate compared with theophylline for mild-to-moderate asthma.

BACKGROUND: The inhaled corticosteroid, fluticasone propionate, was compared with the oral bronchodilator theophylline in the maintenance treatment of asthma. OBJECTIVE: The objective of the present study was to compare the efficacy and safety of twice-daily inhaled fluticasone propionate, 50 micrograms, and fluticasone propionate, 100 micrograms, with that of theophylline in the maintenance treatment of mild-to-moderate asthma. METHODS: In this randomized, double-blind, placebo-controlled, parallel-group study, 353 adult and adolescent patients with asthma inadequately controlled with inhaled beta-agonist therapy alone received fluticasone propionate, 50 micrograms, or fluticasone propionate, 100 micrograms, by metered-dose inhaler; theophylline capsules; or placebo twice daily for 12 weeks. Only inhaled albuterol was permitted as needed for acute symptoms. RESULTS: Both fluticasone propionate groups had a significantly greater probability of remaining in the study (ie, meeting asthma stability criteria) than did either the theophylline or placebo group (P < or = .008); 39% and 51% in the theophylline and placebo groups, respectively, were withdrawn due to lack of treatment efficacy compared with 14% and 21% in the fluticasone propionate, 50 micrograms, and fluticasone propionate, 100 micrograms, groups. Both fluticasone propionate groups experienced significantly greater improvement in FEV1 and PEF compared with patients in the theophylline or placebo group (P < or = .004). The incidence of potentially drug-related adverse events was significantly greater in the theophylline group (25%) than in the placebo group (11%) (P = .031), while there were no differences between placebo and fluticasone propionate, 50 micrograms, (18%) or fluticasone propionate 100 micrograms, (22%). CONCLUSION: Twice daily treatment with inhaled fluticasone propionate 50 micrograms or 100 micrograms was significantly more effective than theophylline in the treatment of mild-to-moderate asthma.

Administration, Inhalation↗
PubMed2006

Ritonavir-fluticasone interaction causing Cushing syndrome in HIV-infected children and adolescents.

BACKGROUND: Ritonavir, a potent inhibitor of CYP3A4 enzyme, can lead to high systemic concentrations of fluticasone when these 2 drugs are coadministered. Exogenous Cushing syndrome (CS) in HIV-infected patients receiving ritonavir and fluticasone has been reported frequently in adults but not in children. Three patients, all receiving ritonavir-fluticasone, developed weight gain and altered fat distribution concerning for either lipodystrophy or CS. METHODS: Three patients were initially identified by their clinicians as having weight gain and altered fat distribution concerning for either lipodystrophy or CS. All 3 patients were receiving fluticasone and ritonavir, leading to concern about a potential medication interaction. After suspecting exogenous CS, all patient medication lists were reviewed to identify all children prescribed ritonavir-fluticasone. Blood adrenocorticotropic hormone (ACTH) and cortisol were obtained during routine clinic visits. Medication history, laboratory data and physical examination findings were abstracted from medical records. RESULTS: Seventeen (9%) of 189 patients in this pediatric HIV clinic had been prescribed ritonavir-fluticasone. Of 7 patients still taking ritonavir-fluticasone, CS features were present in 4 (57%) patients, including the 3 patients initially suspected of CS or lipodystrophy. Five (71%) patients, including all 4 with CS features, had low serum concentrations: median cortisol <0.2 microg/dL (normal, <0.2 microg/dL). Three of these 5 had ACTH measured, all of which were low: median ACTH 3.0 pmol/L (range, 2.2-<5.0 pmol/L). One patient taking ritonavir-fluticasone had suppressed cortisol but no CS features. The 2 patients with normal serum cortisol and ACTH values had persistent HIV viremia and were suspected of medication nonadherence. Clinical and laboratory abnormalities generally normalized in affected patients within 3 months after discontinuation of fluticasone alone (2) and ritonavir-fluticasone (3). CONCLUSIONS: Pediatric HIV physicians frequently prescribe fluticasone and ritonavir together. The combination can cause CS and adrenal suppression in children, potentially leading to misdiagnosis of lipodystrophy syndrome and to increased risk of adrenal crisis during acute illness. Alternatives to fluticasone should be used for treating children receiving ritonavir.

Adolescent↗
PubMed1997

Efficacy of inhaled fluticasone propionate in asthma results from topical and not from systemic activity.

The objective of this study was to determine whether the therapeutic benefits of inhaled fluticasone propionate are mediated through topical or systemic effects. Two hundred seventy-four patients with asthma receiving beclomethasone dipropionate or triamcinolone acetonide during a 2-wk, single-blind, run-in period were randomized to inhaled fluticasone propionate powder 100 or 500 micrograms twice daily, oral fluticasone propionate 20 mg once daily, or placebo during a 6-wk treatment period. Patients receiving inhaled fluticasone propionate had a significantly greater probability of remaining in the study over time compared with patients receiving oral fluticasone propionate or placebo (p = 0.001). FEV1 and PEF rates at end point were significantly higher with inhaled fluticasone propionate treatment regimens than with oral fluticasone propionate (with the exception of PEF rates for inhaled fluticasone propionate 100 micrograms) or placebo treatments (p < or = 0.004). Systemic exposure to fluticasone propionate as assessed by trough plasma concentrations and/or 12-hr plasma concentration area under the curve analyses (AUC12) was higher with the oral fluticasone propionate than with the two inhaled fluticasone propionate treatment groups. The results of this study suggest that the therapeutic benefits of inhaled fluticasone propionate are mediated through topical effects in the lungs and not through systemic effects.

Administration, Inhalation↗