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Comparison of bronchoprotective and bronchodilator effects of a single dose of formoterol delivered by hydrofluoroalkane and chlorofluorocarbon aerosols and dry powder in a double blind, placebo‐controlled, crossover study
Author(s) -
Houghton C. M.,
Langley S. J.,
Singh S. D.,
Holden J.,
Monici Preti A. P.,
Acerbi D.,
Poli G.,
Woodcock A.
Publication year - 2004
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2004.02172.x
Subject(s) - dry powder inhaler , medicine , inhaler , bronchodilator , chlorofluorocarbon , metered dose inhaler , crossover study , formoterol , placebo , anesthesia , spirometry , inhalation , tolerability , methacholine , asthma , pharmacology , adverse effect , lung , respiratory disease , chemistry , alternative medicine , organic chemistry , pathology , budesonide
Background In response to the phasing out of chlorofluorocarbon (CFC) inhalers, a metered dose hydrofluoroalkane (HFA) formulation, Modulite (Chiesi Farmaceutici S.p.A, Parma, Italy), to be delivered with a pressurized metered dose inhaler (pMDI), has been developed. Modulite is a HFA formulation technology that has been designed to provide stable and uniform dose delivery of HFA‐based formulations to enable an easy transition from CFC to HFA inhalers. Objectives The aim of this study was to compare the bronchoprotective and bronchodilator effects of a single dose of 12 µg of formoterol from the HFA Modulite inhaler with the Foradil Aerolizer (dry powder inhaler, DPI) and the Foradil CFC inhalers (Novartis Health Consumer, Basel, Switzerland). Methods This was a double blind, double dummy, randomized, placebo‐controlled, crossover study conducted in 38 subjects with mild to moderate asthma (mean forced expiratory volume in 1 s [FEV 1 ] 87.5% predicted). The primary endpoint was methacholine challenge provocative dose required for 20% fall in the FEV 1 (PD 20 ) 90 min post dose. Bronchodilation was assessed with spirometry (FEV 1 , FVC, FEF 25–75 ) and impulse oscillometry (resistance at 5 and 20 Hz, reactance at 5 Hz and resonant frequency) over the 90 min post dose. In a subset of 12 subjects formoterol plasma levels, serum potassium and glucose were determined up to 480 min post dose. Results The three formoterol formulations demonstrated significant ( P ≤ 0.05) improvements in bronchoprotection compared to placebo and non‐inferiority of the HFA preparation compared to the CFC and DPI preparations was demonstrated. Geometric mean PD 20 values were 0.51 mg with HFA, 0.62 mg with DPI, 0.62 mg with CFC and 0.2 mg with placebo. The log transformed mean differences in PD 20 doubling dose between HFA and (a) DPI was −0.28 (95% CI −0.84–0.29, P = 0.57) (b) CFC was −0.28 (95% CI −0.84–0.28, P = 0.57) and (c) placebo was 1.38 (95% CI 0.82–1.94, P < 0.001). Serum potassium, glucose and formoterol plasma profiles were comparable for the CFC, HFA and DPI devices. Conclusion Our findings of similar efficacy, pharmacokinetics and systemic effects of the HFA formoterol inhaler compared to the CFC and DPI preparations supports the potential use of this novel formulation in the treatment of asthma.