Pharmacokinetic comparison of beclomethasone dipropionate extrafine aerosol from two inhaler devices in children with asthma

详细信息    查看全文

• 作者：Lester I. Harrison ; Sarala Kurup ; Lin-Zhi Chen ; Bruce P. Ekholm ; Timothy G. Wighton and Gail G. Shapiro
• 刊名：European Journal of Clinical Pharmacology
• 出版年：2002
• 出版时间：June 2002
• 年：2002
• 卷：58
• 期：3
• 页码：191-195
• 全文大小：89 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Pharmacology and Toxicology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-1041

文摘

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 µg BDP as four inhalations from 50 µg/actuation P&B, 200 µg BDP as four inhalations from 50 µg/actuation AH, and 400 µg BDP as four inhalations from 100 µg/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 (Cmax) 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 Cmax and AUC between the 200-µg and 400-µg 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.