Premium
Pharmacokinetics of inhaled monodisperse beclomethasone as a function of particle size
Author(s) -
EspositoFesten J. E.,
Zanen P.,
Tiddens H. A. W. M.,
Lammers J.W. J.
Publication year - 2007
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.1365-2125.2007.02894.x
Subject(s) - pharmacokinetics , bioavailability , beclometasone dipropionate , chemistry , particle size , crossover study , aerosol , chromatography , dispersity , area under the curve , aerodynamic diameter , pharmacology , medicine , respiratory disease , lung , organic chemistry , alternative medicine , pathology , placebo
What is already known about this subject • For asthmatic adults, bronchodilators with a MMAD between 3 and 6 µm were shown to give the best improvement in lung function and the least systemic side‐effects. • It is not known, however, what is the most efficacious particle size for inhaled steroids in asthmatic adults. Clinical efficacy and systemic side‐effects of inhaled steroids should be measured to define the optimal particle size. What this study adds • Our study investigated the systemic absorption of inhaled steroids. We found that a particle size of 2.5 µm and 4.5 µm gave a higher pulmonary bioavailability compared with the 1.5 µm monodisperse aerosols in adults with mild asthma and therefore were more likely to elicit systemic adverse effects. Aims For optimal efficacy, antiasthma drugs should be delivered to the desired region in the airways. To date, the optimal particle size for steroids in adults is not known. The aim of the study was to evaluate the pulmonary bioavailability for inhaled beclomethasone dipropionate (BDP) aerosols of different particle sizes. Methods In a randomized single‐blind crossover trial, 10 mild asthmatic patients inhaled monodisperse BDP aerosols with mass median aerodynamic diameters (MMADs) of 1.5, 2.5 and 4.5 µm. Gastrointestinal absorption was blocked by activated charcoal. Plasma concentrations of 17‐beclomethasone monopropionate (17‐BMP) were measured by liquid chromatography plus mass spectrometry. Results Aerosols with MMADs of 1.5 µm, 2.5 µm, and 4.5 µm gave mean maximum concentrations ( C max ) of 17‐BMP of 475 pg ml −1 , 1300 pg ml −1 , and 1161 pg ml −1 , respectively. The area under the curve (AUC) values of 17‐BMP for MMADs of 1.5 µm, 2.5 µm, and 4.5 µm were 825 pg ml −1 h, 2629 pg ml −1 h, and 2276 pg ml −1 h, respectively. The mean terminal half‐time of 17‐BMP for all three aerosol sizes was around 1.5 h. Conclusions Monodisperse BDP aerosols with a MMAD of 1.5 µm gave two‐three fold lower values for C max and AUC than those with MMADs of 2.5 and 4.5 µm.