Pharmacokinetic comparison of beclomethasone dipropionate extrafine aerosol from two inhaler devices in children with asthma.
OBJECTIVE
The primary objective was to test the comparability of the pharmacokinetics of beclomethasone dipropionate (BDP) delivered from a pressurized extrafine solution formulation in two inhalation devices in children with asthma. One inhaler was actuated using the press and breathe (P&B) technique and the other was breath-actuated (AH); both inhalers used HFA-134a as propellant.


METHODS
Eighteen children aged between 9 years and 12 years entered and completed the study; written informed consent was obtained from all patients and their legal guardians. Each patient received, according to a randomized three-period crossover design, 200 microg BDP as four inhalations from 50 microg/actuation P&B, 200 microg BDP as four inhalations from 50 microg/actuation AH, and 400 microg BDP as four inhalations from 100 microg/actuation AH. Each patient was instructed on the proper use of each device once, at the screening visit. Patients self-administered all inhalations at the same time of day during the study without further coaching. Blood samples were collected for 24 h during each period to assay for the presence of BDP and metabolites. The log-transformed pharmacokinetic data were compared using a confidence-interval approach.


RESULTS
Almost all the BDP-derived material in the plasma was the active metabolite beclomethasone 17-monopropionate; pharmacokinetic analyses were only performed for this metabolite. The ratios each of the pharmacokinetic parameters maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC), between the AH and P&B inhaler devices, were 0.94 and 1.1, respectively, and the corresponding 95% confidence intervals demonstrated comparability of the devices. Dose proportionality of C(max) and AUC between the 200-microg and 400-microg doses was similarly shown. About twice as many inhalation errors occurred during the P&B administration as during the AH periods, but the incidence was still low and did not result in any change in pharmacokinetics.


CONCLUSIONS
The rate and extent of drug absorption was comparable from the P&B and AH inhaler devices in children with asthma. Dose proportionality was also observed.
Harrison
Lester I
LI
Research and Development Laboratory, 3M Pharmaceuticals, 3M Center Building 270-3S-05, St. Paul, MN 55144, USA. liharrison@mmm.com
Kurup
Sarala
S
Chen
Lin-Zhi
LZ
Ekholm
Bruce P
BP
Wighton
Timothy G
TG
Shapiro
Gail G
GG
D000336:Aerosols; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001507:Beclomethasone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D016001:Confidence Intervals; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D009330:Nebulizers and Vaporizers
D000336:Aerosols; D018927:Anti-Asthmatic Agents; D001507:Beclomethasone