Optimal dose selection of fluticasone furoate nasal spray for the treatment of seasonal allergic rhinitis in adults and adolescents

Martin, Bruce G.; Ratner, Paul H.; Hampel, Frank C.; Andrews, Charles P.; Toler, T.; Wu, Wei; Faris, Melissa; Philpot, E.

doi:10.2500/aap.2007.28.2983

Cited by 70 publications

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“…Fluticasone furoate, administered as an intranasal aqueous suspension via a unique side-actuated device, is a new chemical entity for the treatment of nasal and ocular symptoms of allergic rhinitis (Martin et al, 2007). As such, it is important to gain an understanding of the metabolism and disposition of fluticasone furoate in humans.…”

Section: Discussionmentioning

confidence: 99%

Metabolism and Disposition of Fluticasone Furoate, an Enhanced-Affinity Glucocorticoid, in Humans

Hughes

Shardlow²,

Hollis³

et al. 2008

Drug Metab Dispos

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ABSTRACT:The purpose of this study was to investigate the metabolism and disposition of fluticasone furoate, an enhanced-affinity glucocorticoid receptor agonist, in humans. In a two-part, open-label design study, five healthy male subjects received a p. Fluticasone furoate [(6␣,11␤,16␣,17␣)-6,9-difluoro-17-{[(fluoromethyl)-thio]carbonyl}-11-hydroxy-16-methyl-3-oxoandrosta-1,4-dien-17-yl-2-furancarboxylate] is a new enhanced-affinity glucocorticoid receptor agonist. It is a synthetic fluorinated corticosteroid that has been developed as an intranasal treatment for patients with symptoms of rhinitis. Fluticasone furoate, otherwise known as GW685698X, is not a salt or prodrug because the entire molecule is required for pharmacological activity. It has similar or greater potency than other clinically used corticosteroids (including mometasone furoate, budesonide, fluticasone propionate, and the active principle of ciclesonide) for the glucocorticoid receptor and against the proinflammatory transcription factors nuclear factor B (NF-B), activation protein-1, and tumor necrosis factorinduced interleukin-8 cytokine production (Salter et al., 2007). Agonism of the glucocorticoid receptor is known to suppress the activation of downstream transcription factors, such as NF-B and activation protein-1, and to activate the glucocorticoid response element transactivation pathway (Rhen and Cidlowski, 2005). Inhibition of the NF-B pathway, in particular, is thought to be intimately involved in the anti-inflammatory activity of glucocorticoids because it is a key pathway in the synthesis of a number of inflammatory cytokines (Karin et al., 2004). It is well documented that topical glucocorticoids interact with many of the inflammatory pathways, and there is a large body of clinical evidence to support their use for the treatment of rhinitis, asthma, and chronic obstructive pulmonary disease (Goodman and Gilman, 2006). The purpose of the present study was to investigate the metabolism and disposition of [ 14 C]fluticasone furoate after p.o. and i.v. administration to healthy male subjects. These dose routes were used as surrogates for the intranasal and inhalation routes, from which the majority of the dose is likely to be swallowed. The p.o. route acted as a surrogate for the portion of an intranasal or inhaled dose that is swallowed, and the i.v. route represented the portion absorbed locally into the systemic circulation.

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Section: Discussionmentioning

confidence: 99%

Metabolism and Disposition of Fluticasone Furoate, an Enhanced-Affinity Glucocorticoid, in Humans

Hughes

Shardlow²,

Hollis³

et al. 2008

Drug Metab Dispos

View full text Add to dashboard Cite

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“…The favorable effect of INSs on ocular symptoms [44] was supported by recent studies which included treatment with INSs agents: mometasone furoate (MF) [18,19,20,21], fluticasone furoate (FF) [22,23,24,25,26,27,28], fluticasone propionate (FP) [29,30], budesonide [31], and (to some degree) triamcinolone acetonide (TA) [32] and beclomethasone dipropionate (BDP) aqueous nasal spray [33,34]. However, the effects of INSs on ocular symptoms were inconsistent across some separate studies [37,40].…”

Section: Introductionmentioning

confidence: 87%

“…FFNS provided consistent positive effects on the ocular symptoms of SAR, compared with placebo, across the 6 prospective trials [22,23,24,25,26,27,28,45]. These effects were consistent across different allergy seasons and geographic locations, and were considered to be robust owing to the consistent use of ocular symptom scores to determine ocular efficacy [45].…”

Section: Introductionmentioning

confidence: 95%

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Should Intranasal Corticosteroids Be Used for the Treatment of Ocular Symptoms of Allergic Rhinoconjunctivitis? A Review of Their Efficacy and Safety Profile

Lightman

Scadding²

2012

Int Arch Allergy Immunol

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Allergic rhinoconjunctivitis (ARC) presents as nasal symptoms, eye watering and additional signs of ocular allergy (e.g. itchy/burning eyes). Intranasal corticosteroids (INSs) are the most effective treatment for the nasal symptoms of seasonal allergic rhinitis (SAR; based on 4 meta-analyses) and are considered first-line therapy when nasal congestion forms a substantial component of the patient’s rhinitis symptoms. Clinical trial evidence shows that INSs also provide some relief from ocular symptoms of SAR and seasonal ARC in adults. INSs probably alleviate eye watering, the main ocular symptom of SAR, by relieving nasal congestion. Other ocular symptoms also improve with INSs. The mechanism for this effect is unknown, but might relate to naso-ocular reflex reduction. There are limited data on ocular safety with INSs. However, the literature supports the use of INSs over several months as there appears to be no considerable increase in the risk of ocular hypertension or glaucoma.

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“…33 Two other published studies support this conclusion. 34,35 Although the mechanism of action of intranasal steroid sprays in relieving ocular symptoms is not understood, several mechanisms have been proposed. By decreasing nasal inflammation, intranasal steroids may modulate or normalize the excess stimulation of reflex neural activity that occurs during allergic reactions, thereby reducing ocular symptoms.…”

mentioning

confidence: 99%

Nasal-Ocular Reflexes and Their Role in the Management of Allergic Rhinoconjunctivitis With Intranasal Steroids

Baroody

Naclerio

2011

World Allergy Organization Journal

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Allergic rhinitis is a common disorder and involves the reaction to environmental allergens with resultant nasal and eye symptoms. The pathophysiologic mechanisms of the eye symptoms in allergic conjunctivitis include a direct effect on the eye by deposited allergen and indirect effects related to the deposition of allergen in the nasal mucosa. One of these proposed mechanisms is the existence of a nasal-ocular reflex whereby the nasal allergic reaction leads to an afferent reflex response, the efferent limb of which results in eye symptoms. Among the treatments available for allergic rhinitis, intranasal steroids are most efficacious for nasal symptoms and have also shown sizeable efficacy related to eye symptoms. We speculated that the effect of intranasal steroids on eye symptoms in allergic rhinitis was related to their inhibition of the nasal-ocular reflex and present data previously generated from our laboratory to support this assumption in a nasal challenge model. Key Words: Nasal-ocular reflex, allergic rhinoconjuctivitis, nasal challenge, intranasal steroids (WAO Journal 2011; 4:S1-S5) A llergic rhinitis is characterized by an IgE-mediated reaction to environmental allergens. It is a common disorder affecting up to 40 million Americans with adult prevalence estimates ranging from 10 to 30% and pediatric prevalence estimates as high as 40% rendering it the most common chronic condition in children. 1 Several reports also support substantial increases in the prevalence of allergic rhinoconjunctivitis (AR) in developed countries in recent decades making it an important health problem. [1][2][3] Although often referred to as allergic rhinitis, this disease actually involves eye symptoms in addition to the nasal symptoms, hence the more appropriate term, AR. In fact, recent epidemiologic data has shown that ocular symptoms, defined as 'episodes of watery, itchy eyes,' affected 40% of the adult population of the United States during a 12-month period. 4 Another study showed that the incidence of conjunctivitis was high (ϳ88%) in patients experiencing allergic rhinitis during the cypress pollen season. 5 Ocular symptoms are not only common, but also distressing for allergy sufferers, with more than 50% stating that watery and red/itchy eyes were moderately to extremely bothersome in the Allergies in America survey. 6 Furthermore, in 15% of sufferers, the ocular component of the allergic hypersensitivity reaction was the most bothersome symptom. 6 In addition to the typical nasal and eye symptoms, AR leads to a significant impairment of the quality of life of its sufferers when measured by both generic and specific quality of life instruments. 7,8 Also associated with the disease are fatigue and daytime sleepiness, 7,9 reduced work productivity, 10 -12 impaired cognitive functioning, 13,14 reduced learning abilities, 15 and impaired sleep. 16 The high prevalence of this benign, but chronic, condition, its adverse effects on quality of life, work performance, and productivity on the job, and the treat...

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Optimal dose selection of fluticasone furoate nasal spray for the treatment of seasonal allergic rhinitis in adults and adolescents

Cited by 70 publications

References 0 publications

Metabolism and Disposition of Fluticasone Furoate, an Enhanced-Affinity Glucocorticoid, in Humans

Metabolism and Disposition of Fluticasone Furoate, an Enhanced-Affinity Glucocorticoid, in Humans

Should Intranasal Corticosteroids Be Used for the Treatment of Ocular Symptoms of Allergic Rhinoconjunctivitis? A Review of Their Efficacy and Safety Profile

Nasal-Ocular Reflexes and Their Role in the Management of Allergic Rhinoconjunctivitis With Intranasal Steroids

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