Fluticasone Furoate, a Novel Inhaled Corticosteroid, Demonstrates Prolonged Lung Absorption Kinetics in Man Compared with Inhaled Fluticasone Propionate
| Autor: | Ann Allen, Vicki Rousell, Philippe Bareille |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Adult
Male Agonist medicine.medical_specialty Metabolic Clearance Rate medicine.drug_class Chemistry Pharmaceutical Biological Availability Pharmacology Glucocorticoid receptor binding Fluticasone propionate Absorption chemistry.chemical_compound Internal medicine Administration Inhalation medicine Humans Pharmacology (medical) Original Research Article Lung Fluticasone Asthma Cross-Over Studies Inhalation Nebulizers and Vaporizers Middle Aged medicine.disease Bronchodilator Agents Androstadienes Endocrinology chemistry Area Under Curve Delayed-Action Preparations Corticosteroid Vilanterol Half-Life medicine.drug |
| Zdroj: | Clinical Pharmacokinetics |
| ISSN: | 0312-5963 |
| DOI: | 10.1007/s40262-012-0021-x |
| Popis: | Background Fluticasone furoate (FF; GW685698) is a novel inhaled corticosteroid that is active at 24 h and under development for once-daily administration in combination with the long-acting β2-adrenoceptor agonist vilanterol (GW642444) for chronic obstructive pulmonary disease and asthma. In vitro studies examining the respiratory tissue-binding properties of corticosteroids showed FF to have the largest cellular accumulation and slowest rate of efflux compared with other clinically used inhaled corticosteroids, consistent with greater tissue retention. The enhanced affinity of the glucocorticoid receptor binding of FF, coupled with its extended tissue association, may be expected to lead to greater and more prolonged anti-inflammatory effects and should provide relevant once-daily efficacy. Objective The aim of this study was to assess the rate and extent of systemic absorption of FF from the lung following inhaled administration of FF from three exploratory dry powder formulations (via DISKHALER®) compared with inhaled fluticasone propionate (FP) [via DISKHALER®] using deconvolution analysis. Methods This open-label, part-randomized, six-way crossover study evaluated three early development dry powder inhaled formulations of FF administered as single doses via DISKHALER®. Healthy male subjects (n = 24) each received FF (2,000 μg; three formulations), inhaled FP (1,000 μg; via DISKHALER®) and 250 μg of each molecule by intravenous infusion. The bioavailability of both inhaled FF and FP represents absorption from the lung as the oral bioavailability from the swallowed portion of the inhaled dose is negligible ( |
| Databáze: | OpenAIRE |
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