Evaluation of in vitro Penetration of Fluticasone Propionate from MP-AzeFlu and Fluticasone Propionate Nasal Spray Through EpiAirway™606 Tissues Using Vertical Diffusion Cells.

PURPOSE: Most patients with allergic rhinitis (AR) have moderate-to-severe disease, requiring complete and prompt relief when symptoms occur. The time course of fluticasone propionate (FP) penetration into nasal tissues after intranasal administration is not well characterized. The goal of this proof-of-concept study was to evaluate the mucosal penetration of FP from fixed-combination FP-azelastine nasal spray (MP-AzeFlu) compared with an FP-only nasal spray in an in vitro, 3-dimensional human bronchial tissue model. MATERIALS AND METHODS: Absorption of FP from MP-AzeFlu and FP nasal spray was modeled using EpiAirway™606 (MatTek Corporation; Ashland, MA, USA) tissue cultured in vertical diffusion cells. The dosing amount of MP-AzeFlu was optimized in a pilot study. Based on the results of the pilot study, 10 µL of MP-AzeFlu (3.65 µg; n = 8) and 10 µL of FP nasal spray (5.00 µg; n = 8) were evaluated for penetration of tissue. Tissue integrity was monitored with Lucifer yellow. FP in the receiving media was quantified for each sample using liquid chromatography with tandem mass spectrometry. RESULTS: MP-AzeFlu and FP nasal spray were associated with similar FP accumulation profiles in the receiving media, but the permeability of FP was greater for MP-AzeFlu during hours 0 to 6, suggesting faster absorption for MP-AzeFlu. No indications of compromised tissue integrity were found in any of the tested cells. CONCLUSION: The higher and more rapid penetration of FP from MP-AzeFlu supports the use of MP-AzeFlu for patients with AR, particularly when prioritizing fast and pronounced symptom relief.

Glycopyrrolate causes prolonged bronchoprotection and bronchodilatation in patients with asthma.

INTRODUCTION: Inhaled anticholinergic drugs are effective bronchodilators in the treatment of COPD, and tiotropium bromide has recently been introduced as a once-daily bronchodilator for use as a maintenance treatment. Racemic glycopyrrolate is an anticholinergic drug that has been used orally to control gastric acidity, parenterally as an antisialogogue and to reverse neuromuscular blockade, and has been studied by inhalation for asthma and COPD. DESIGN AND OBJECTIVE: We investigated the duration of protection against the constrictor effects of inhaled methacholine of a single dose of inhaled nebulized racemic glycopyrrolate (0.5, 1.0, and 2.0 mg) compared with ipratropium bromide (0.5 mg) and placebo in 10 atopic asthmatic volunteers in a double-blind, five-way, crossover study. RESULTS: Protection against methacholine-induced bronchospasm after administering glycopyrrolate was maintained to 30 h, the last time point measured. Both bronchodilatation and bronchoprotection were significantly longer with glycopyrrolate than after ipratropium bromide, and bronchoprotection was significant at all time points from 2 to 30 h compared to placebo. Dryness of the mouth and nose was described in 18% of patients after the highest dose of glycopyrrolate. CONCLUSIONS: The prolonged bronchodilator response and the protection against methacholine-induced bronchospasm demonstrated in asthma suggests that inhaled racemic glycopyrrolate would be superior to ipratropium bromide for treatment of stable COPD.