Background: Fluticasone propionate is a glucocorticoid with negligible oral bioavailability and very low intranasal bioavailability that is used as an intranasal spray for the treatment of rhinitis.Objective: The purpose of this study was to evaluate the hypothalamic-pituitary-adrenal (HPA)-axis effects of fluticasone propionate aqueous nasal spray (FP ANS) compared with oral prednisone and placebo by using a 6-hour cosyntropin infusion test.Methods: In a 4-week, randomized, double-blind, double-dummy, placebo-controlled parallel-group study, 105 adult patients with allergic rhinitis were randomly assigned to receive FP ANS 200 mu g once daily, FP ANS 400 mu g twice daily, oral prednisone 7.5 mg once daily, oral prednisone 15 mg once daily, or placebo. HPA-axis function was assessed at the screening visit and after 4 weeks of treatment by measuring morning plasma cortisol concentrations and poststimulation concentrations of plasma and urinary cortisol.Results: There was no evidence of altered HPA-axis response to cosyntropin by the end of treatment with FP ANS 200 mu g once daily or FP ANS 400 mu g twice daily when compared with placebo. In contrast, 4 weeks of treatment with oral prednisone 7.5 or 15 mg once daily was associated with significant (p < 0.05 vs placebo) reduction in HPA-axis function, as evidenced by lower plasma cortisol concentrations (area under the plasma concentration-time curve and peak concentrations) after cosyntropin stimulation and reduced mean 24-hour urinary cortisol excretion. FP ANS 400 mu g twice daily and both prednisone regimens were associated with a significant (p < 0.05 vs placebo) reduction in mean morning plasma cortisol concentrations.Conclusion: These results indicate that a 4-week course of FP ANS at four times the recommended dose does not suppress adrenal function in response to a 6-hour cosyntropin stimulation test.

Cytokines active on eosinophils are important in the pathogenesis of allergic diseases. A study was conducted to determine if nasal eosinophilia in allergic rhinitis is associated with an increase in eosinophil-active cytokines in nasal secretions and to compare the effects of fluticasone propionate aqueous nasal spray with astemizole and placebo on the levels of these cytokines. Forty-five patients with moderately severe ragweed allergic rhinitis were randomly assigned to receive 2 weeks of treatment with fluticasone propionate aqueous nasal spray 200 micrograms once daily, astemizole 10 mg once daily, or placebo. Nasal lavage was performed in July (preseason), August (peak season), September (after 2 weeks of treatment), and October (postseason). The number of eosinophils, the amount of eosinophil-derived neurotoxin (EDN), and the amount of eosinophil survival-enhancing activity were measured. Total mean nasal symptom scores, concentrations of nasal eosinophils and EDN, and eosinophil survival-enhancing cytokine activity in nasal secretions were significantly lower after 2 weeks of treatment with fluticasone propionate compared with astemizole or placebo. Survival-enhancing activity was detected in the nasal secretions of 25 patients. By blocking activity with monoclonal antibodies, specific cytokines were identified (granulocyte macrophage-colony stimulating factor, 3 samples; interleukin-3, 2 samples; interleukin-5, 5 samples). In conclusion, eosinophil-active cytokine concentrations parallel the nasal symptoms of patients with ragweed allergic rhinitis. Unlike astemizole, fluticasone propionate significantly lowers cytokine activity in nasal tissue, which may contribute to the therapeutic efficacy of the drug.

Background: Comparative studies with topical corticosteroids and antihistamines for treatment of allergic rhinitis have not always demonstrated clear distinctions between the two on the basis of therapeutic efficacy.Objective: This study was designed to compare the efficacy and tolerability of fluticasone propionate aqueous nasal spray with those of terfenadine in the treatment of seasonal allergic rhinitis.Methods: Three hundred forty-eight patients with allergic rhinitis were given fluticasone propionate aqueous nasal spray (200 mu g once daily), terfenadine tablets (60 mg twice daily), or placebo for 4 weeks in a multicenter, randomized, double-blind, double-dummy, parallel-group study.Results: Clinician-rated total nasal symptom scores after 1, 2, 3, and 4 weeks of therapy and patient-rated total nasal symptom scores throughout treatment were significantly (p < 0.05) lower in the fluticasone propionate group compared with the terfenadine group or the placebo group. Terfenadine was not statistically different from placebo on the basis of clinician-rated nasal symptom scores, except for sneezing. Total nasal airflow, measured by rhinomanometry, significantly (p < 0.05) improved in the fluticasone propionate group compared with the terfenadine group or the placebo group. More fluticasone propionate-treated patients compared with the place-treated patients has reduced nasal mucosal eosinophil counts after 4 weeks of therapy (p < 0.05). No serious or unusual drug-related adverse events were reported. Morning plasma cortisol concentrations after 4 weeks of therapy did not differ among groups.Conclusion: Fluticasone propionate aqueous nasal spray is more effective than terfenadine tablets for treatment of seasonal allergic rhinitis.

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.

This two-week, double-blind, randomized, parallel-group, placebo-controlled study examined the efficacy and tolerability of intranasal fluticasone propionate (200 mcg once daily or 100 mcg twice daily) in 12- to 17-year-old adolescents (n = 243) with seasonal allergic rhinitis. Both clinician- and patient-rated symptom scores for nasal obstruction, sneezing, nasal itching, and rhinorrhea were significantly lower in the groups treated with intranasal fluticasone propionate compared with the placebo-treated group. Clinician ratings of overall response to therapy also were significantly more favorable for each intranasal fluticasone propionate dosing regimen compared with placebo. There were no statistically significant differences between the intranasal fluticasone propionate groups in nasal symptom scores or clinician-rated overall response to therapy. No severe or unusual adverse events were reported in any of the groups. Morning plasma cortisol concentrations after 2 weeks of therapy did not differ among groups. These data indicate that intranasal fluticasone propionate 200 mcg once daily and 100 mcg twice daily are equally effective and well-tolerated in adolescents with seasonal allergic rhinitis.

Purpose: To evaluate the efficacy and tolerability of intranasally administered fluticasone propionate, 200 mu g or 100 mu g (half the adult dosage) when administered once daily for 4 weeks to children with seasonal allergic rhinitis. Design and selling: Double-blind, randomized, placebo-controlled, parallel-group clinical study in 10 pediatric outpatient centers. Subjects: Children (n = 249), 4 to 11 years of age, with moderate to severe symptoms of seasonal allergic rhinitis, positive skin test reaction to a local autumn allergen, and a history of seasonal allergic rhinitis. Measurements: Clinician- and patient-rated nasal symptom scores (obstruction, rhinorrhea, sneezing, itching), clinician-rated assessment of overall response to treatment, patient-rated nasal obstruction on awakening, and use of rescue medication. Clinicians questioned patients (or parents) regarding symptoms and adverse events. Morning plasma cortisol concentrations and 24-hour urinary excretion of cortisol and 17-ketogenic steroids were evaluated. Results: Intranasal fluticasone propionate, 200 mu g or 100 mu g once daily, was significantly more effective than placebo in the treatment of seasonal allergic rhinitis in children. Clinician- and patient-rated symptom scores indicated greater improvement in nasal symptoms, including nasal obstruction On awakening, among patients receiving intranasal fluticasone propionate. Overall response to treatment was also significantly greater in the active treatment groups. The two fluticasone propionate groups were not statistically different. Mean morning plasma cortisol concentrations and 24-hour urinary excretion of free cortisol and 17-ketogenic steroids were similar across all groups both before and after treatment. Conclusions: Intranasal fluticasone propionate, 100 mu g (half the adult dose) or 200 mu g given once daily for 4 weeks is effective and well tolerated in children 4 to II years of age with seasonal allergic rhinitis.

BACKGROUND:Nasal cytograms of patients with allergic rhinitis contain increased numbers of eosinophils and basophilic cells. Neutrophils are also more numerous in cytograms of allergic persons. Topical intranasal corticosteroid therapy for allergic rhinitis has been shown to decrease the numbers of some inflammatory cell types. Fluticasone propionate aqueous nasal spray, a potent synthetic corticosteroid preparation, is effective therapy for seasonal and perennial allergic rhinitis.METHODS:Nasal mucosal scrapings were obtained with a Rhinoprobe (Apotex Scientific, Inc. Arlington, Texas) before and after therapy with fluticasone propionate aqueous nasal spray at several doses in patients with either seasonal allergic rhinitis (2 to 4 weeks' therapy) or perennial allergic rhinitis (24 weeks' therapy). More than 1000 paired nasal cytograms obtained from patients participating in five multicenter studies were evaluated.RESULTS:The percentage of patients with nasal eosinophils (p < 0.01, most studies) and basophilic cells (p < 0.05, most studies) decreased significantly after treatment with fluticasone propionate compared with placebo-treated patients. Similar findings were observed with beclomethasone dipropionate in one study. The number of neutrophils remained relatively unchanged after treatment with the intranasal corticosteroids or placebo.CONCLUSIONS:These findings suggest that the therapeutic benefits of topical intranasal fluticasone propionate and beclomethasone dipropionate for the therapy of seasonal and perennial allergic rhinitis are reflected by the decrease in inflammatory cells in the nasal mucosa.

INTRODUCTION:Fluticasone propionate aqueous nasal spray, a new topical corticosteroid preparation, is effective when given as 200 micrograms once daily in patients (> 12 years of age) with seasonal allergic rhinitis.STUDY OBJECTIVE:To evaluate the efficacy and safety of fluticasone proprionate aqueous nasal spray in children aged 4 to 11 years with seasonal allergic rhinitis.STUDY DESIGN:Multicenter, randomized, double-blind, placebo-controlled, parallel-group.PATIENTS:Two hundred fifty children aged 4 to 11 years with moderate-to-severe nasal symptoms, a positive skin test reaction to a late-summer or autumn allergen, a history of seasonal allergic rhinitis, and documentation of an unsatisfactory response to conventional treatment.INTERVENTIONS:Children were randomly assigned to receive fluticasone propionate, either 100 micrograms or 200 micrograms, or placebo, given by intranasal spray once daily in the morning for 14 days.MEASUREMENTS AND RESULTS:Severity of nasal symptoms (obstruction, rhinorrhea, itching, and sneezing) was recorded on visual analog scales by investigators at weekly visits and by patients (or adult guardian) daily in the evening. According to investigator and patient ratings, both fluticasone propionate 100 micrograms/d and 200 micrograms/d lowered total nasal symptom scores when compared with placebo. Both dosages of fluticasone propionate were more effective than placebo on the basis of investigator-rated overall clinical evaluation of efficacy at the end of treatment, with significant improvement (as opposed to moderate or mild improvement, no change or worsening) noted in 21% to 29% of the active-treatment groups vs 9% in the placebo group. There were no significant differences between the two fluticasone propionate dosages in any efficacy measurement. Morning plasma cortisol concentrations and frequency of drug-related adverse events were similar in the fluticasone propionate and placebo groups.CONCLUSION:In children as young as 4 years, 100 micrograms of fluticasone propionate aqueous nasal spray given once daily is as effective as 200 micrograms given once daily, the usual adult dose for the treatment of seasonal allergic rhinitis. Both fluticasone propionate dosages were well tolerated and neither dosage appears to interfere with the hypothalamic-pituitary-adrenal axis in children.

Diethyl phthalate (DEP) and dimethyl phthalate (DMP), phthalic acid ester (PAE) plasticizers, were evaluated for developmental toxicity because of reports in the literature that some PAE were embryotoxic and teratogenic. A previous study (Singh et al., '72) suggested that an increased incidence of skeletal defects in rats might result from gestational exposure to DEP (0.6-1.9 g/kg) or DMP (0.4-1.3 g/kg), ip, on gestational days (gd) 5, 10, and 15. In the current study DEP (0, 0.25, 2.5, and 5%) or DMP (0, 0.25, 1, and 5%) in feed (approximately 0.2-4.0 g/kg/day) were supplied to timed-mated rats from gd 6 to 15. Treatment with 5% DMP resulted in increased relative maternal liver weight. Also, animals exhibited reduced body weight gain during treatment (5% DEP or DMP) and during gestation (5% DEP). Weight gain corrected for gravid uterine weight was also reduced in animals fed 5% DEP. However, high-dose treatment with either DEP or DMP resulted in changes in food and water consumption paralleling the body weight reductions, suggesting that apparent toxic effects on maternal body weight may reflect PAE/feed unpalatability. Treatment with 2.5% DEP resulted in only transient changes in body weight during early treatment. The only maternal effects at 0.25 or 1% DMP were minor changes in food and/or water consumption, and there were no effects at 0.25% DEP. Thus, the NOAELs for maternal toxicity were 1% DMP and 0.25% DEP. In contrast to the observed maternal toxicity, there was no effect of DEP or DMP treatment on any parameter of embryo/fetal development, except an increased incidence of supernumerary ribs (a variation) in the 5% DEP group. These results do not support the conclusion of other investigators that DEP and DMP are potent developmental toxicants. Rather, they suggest that the short-chain PAE are less developmentally toxic than PAE with more complex substitution groups, e.g., di(2-ethylhexyl) phthalate, mono(2-ethylhexyl) phthalate, and butyl benzyl phthalate.