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 mug BDP as four inhalations from 50 mug/actuation PB, 200 mug BDP as four inhalations from 50 mug/actuation AH, and 400 mug BDP as four inhalations from 100 mug/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-mug and 400-mug 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. Conclusion: 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.