Efficacy of Inhaled Fluticasone Propionate in Asthma Results from Topical and Not from Systemic Activity

Abstract

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.

Duration of effect of single-dose inhaled fluticasone propionate on AMP-induced bronchoconstriction

“…ICS are known for their topical anti-inflammatory effects and inhaled FP in particular has a highly favourable topical efficacy compared with systemic safety [19]. This direct topical effect of ICS is supposed to be responsible for the acute clinical effect on FEV1 as soon as 2 h, as demonstrated in a previous study in acute severe asthma [20].…”

Categorizing Asthma Severity: An Overview of National Guidelines

“…When given in the inhaled form, especially at low doses, corticosteroids act as topical anti-inflammatory agents in the airways with little risk of systemic exposure. 2 Inhaled corticosteroids have been shown to effectively reduce airway inflammation, 3,4 control asthma symptoms, improve lung function, decrease exacerbations, 5 and reduce hospitalization 6 and mortality rates 7,8 from asthma. However, as higher doses of inhaled corticosteroids are used the risks of systemic exposure 2 and side effects will correspondingly increase 9 .…”

Establishing bioequivalence for orally inhaled drug products

“…Dr García Arieta suggests this is a misinterpretation of the supporting data we cited [4], arguing that it is simply a matter of tissue distribution and that after oral administration fluticasone propionate distributes to fatty tissues and not to the lungs. The volume of distribution of fluticasone propionate, and indeed of any drug, is a primary pharmacokinetic parameter and independent of its route of administration [5].…”

“…Therefore at steady-state, fluticasone propionate's volume of distribution and its rate and extent of tissue partitioning should be the same for oral and inhaled administration. After single dose administration the rate of tissue distribution may well be relevant, but in the cited study [4], 6 weeks dosing was used and steady-state equilibrium should have been achieved between plasma and tissues compartments. However, despite the higher systemic concentration of fluticasone propionate achieved after oral compared to inhaled dosing, only the inhaled regimens were efficacious, suggesting a lack of equilibrium between the site of action in the lung and the drug concentrations in plasma.…”