Pharmacokinetics of inhaled monodisperse beclomethasone as a function of particle size.
OBJECTIVE
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 microm. 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 microm, 2.5 microm, and 4.5 microm 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 microm, 2.5 microm, and 4.5 microm 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 microm gave two-three fold lower values for C(max) and AUC than those with MMADs of 2.5 and 4.5 microm.
Esposito-Festen
J E
JE
Department of Pediatrics, Division of Respiratory Medicine, Erasmus University Medical Center Rotterdam-Sophia Children's Hospital, Rotterdam, The Netherlands.
Zanen
P
P
Tiddens
H A W M
HA
Lammers
J-W J
JW
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000336:Aerosols; D018927:Anti-Asthmatic Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001249:Asthma / Q000097:blood / Q000378:metabolism*; D001507:Beclomethasone / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D016037:Single-Blind Method
D000336:Aerosols; D018927:Anti-Asthmatic Agents; C065857:beclomethasone 17-monopropionate; D001507:Beclomethasone