Objective: The objectives of this study were to test the Jose and strength proportionalities of beclomethasone dipropionate (BDP) delivered from two strengths of a pressurized extrafine solution formulation. Methods: Thirty adults with mild, stable asthma, aged between 18 years and 70 years, completed the study; written informed consent was obtained from all patients. Each patient received, according to a randomized four-period crossover design, 100 mug BDP as two inhalations from 50-mug/actuation strength, 100 mug BDP as one inhalation from 100-mug/activation strength, 400 mug BDP as eight inhalations from the 50-mug/actuation strength, and 400 mug BDP as four inhalations from the 100-mug/actuation strength. Patients self-administered all inhalations at the same time of day during the study. Blood samples were collected for 12 h during each period to assay for the presence of BDP and metabolites. The log-transformed pharmacokinetic data were compared for proportionality equivalence using a confidence-interval approach. Results: Almost all the BDP-derived material in the plasma was the active metabolite beclomethasone 17-monopropionate (17-BMP). Due to low levels, neither elimination half-life (t(1/2)) nor the area under the plasma concentration-time curve (AUC) for 17-BMP could be calculated for the 100-mug BDP doses. Dose proportionality of the 100-mug and 400-mug BDP doses, using 17-BMP maximum plasma concentration (C-max) was demonstrated for each strength. Strength proportionality of the 50-mug and 100-mug/actuation strengths was observed for C-max at both dose levels and for AUC at the higher dose level. The t(1/2) of 17-BMP was found to be approximately 2.8 h. Conclusion: This study demonstrated both the strength and dose proportionalities of the BDP extrafine aerosol. This important information will allow physicians maximum flexibility in prescribing this aerosol product.
