BDP/福莫特罗 HFA pMDI 在健康志愿者、哮喘患者和 COPD 患者中的肺部沉积。

Lung deposition of BDP/formoterol HFA pMDI in healthy volunteers, asthmatic, and COPD patients.

机构信息

University Hospital Antwerp , Edegem, Belgium.

出版信息

J Aerosol Med Pulm Drug Deliv. 2010 Jun;23(3):137-48. doi: 10.1089/jamp.2009.0772.

DOI:10.1089/jamp.2009.0772

PMID:20109122

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3123836/

Abstract

BACKGROUND

When inhaling medication, it is essential that drug particles are delivered to all sites of lung inflammation, including the peripheral airways. The aim of this study was to assess the lung deposition and lung distribution of beclomethasone dipropionate (BDP)/formoterol (100/6 microg), both dissolved in hydrofluoroalkane (HFA) and delivered by pressurized metered dose inhaler (pMDI) in healthy subjects, asthmatic, and chronic obstructive pulmonary disease (COPD) patients, to investigate how the in vitro characteristics of the formulation translate into the in vivo performance in diseases with different airway obstruction.

METHODS

Healthy volunteers (n = 8), persistent asthmatics (n = 8), and patients with stable COPD (n = 8) completed this open-label, single-dose parallel-group study. Each patient received one single treatment of four puffs of (99 m)Tc-labeled BDP/formoterol formulation. The correlation between particle size distribution of radioactivity and of the drugs in the radiolabeled formulation was validated. Intra- and extrapulmonary deposition, amount of exhaled drug, and the central to peripheral ratio (C/P) were calculated immediately after inhalation. Patients' lung function and pharmacokinetic parameters were also assessed up to 24 h post-dose.

RESULTS

The average lung deposition of BDP/formoterol was 34.08 +/- 9.30% (relative to nominal dose) in healthy subjects, 30.86 +/- 8.89% in asthmatics, and 33.10 +/- 8.90% in COPD patients. Extrathoracic deposition was 53.48% +/- 8.95, 57.64% +/- 9.92 and 54.98% +/- 7.01, respectively. C/P ratios of 1.42 +/- 0.32 in healthy subjects, 1.96 +/- 0.43 in asthmatics, and 1.94 +/- 0.69 for COPD patients confirmed drug distribution to all regions of the lungs. Forced expiratory volume in 1 sec (FEV(1)) increased in all groups after BDP/formoterol inhalation, but was more evident in the patient groups. No significant correlation between baseline lung function and drug deposition was observed. Formoterol, BDP, and beclomethasone 17 monopropionate (B17MP) plasma profiles were comparable between groups.

CONCLUSION

Inhalation of BDP/formoterol HFA (100/6 microg) produces high and homogeneous deposition of BDP and formoterol in the airways, regardless of pathophysiological condition.

摘要

背景

吸入药物时，药物颗粒必须输送到肺部所有炎症部位，包括外周气道。本研究的目的是评估吸入丙酸倍氯米松（BDP）/福莫特罗（100/6μg）在健康受试者、哮喘和慢性阻塞性肺疾病（COPD）患者中的肺部沉积和肺部分布，以研究不同气道阻塞疾病中制剂的体外特性如何转化为体内性能。

方法

健康志愿者（n=8）、持续性哮喘患者（n=8）和稳定期 COPD 患者（n=8）完成了这项开放标签、单剂量平行组研究。每位患者接受四喷放射性标记的 BDP/福莫特罗制剂。验证了放射性标记制剂中药物粒径分布与放射性的相关性。吸入后立即计算内、外肺沉积量、呼出药物量和中央至外周比（C/P）。还评估了患者的肺功能和药代动力学参数，直至给药后 24 小时。

结果

BDP/福莫特罗在健康受试者中的平均肺部沉积率为 34.08±9.30%（相对于名义剂量），在哮喘患者中为 30.86±8.89%，在 COPD 患者中为 33.10±8.90%。胸外沉积率分别为 53.48%±8.95%、57.64%±9.92%和 54.98%±7.01%。健康受试者的 C/P 比值为 1.42±0.32，哮喘患者为 1.96±0.43，COPD 患者为 1.94±0.69，证实药物分布到肺部所有区域。吸入 BDP/福莫特罗后，所有组的 1 秒用力呼气量（FEV1）均增加，但在患者组更为明显。在基线肺功能和药物沉积之间未观察到显著相关性。各组间布地奈德、福莫特罗和丙酸倍氯米松 17-单丙酸酯（B17MP）的血浆谱相似。