评估布地奈德/福莫特罗 Easyhaler(®)在体外和体内的流速依赖性。
Evaluation of in vitro and in vivo flow rate dependency of budesonide/formoterol Easyhaler(®).
机构信息
1 Department of Allergy, Helsinki University Central Hospital , Helsinki, Finland .
出版信息
J Aerosol Med Pulm Drug Deliv. 2014 Oct;27(5):329-40. doi: 10.1089/jamp.2013.1099. Epub 2014 Jun 30.
BACKGROUND
The Easyhaler(®) (EH) device-metered dry powder inhaler containing budesonide and formoterol is being developed for asthma and chronic obstructive pulmonary disease (COPD). As a part of product optimization, a series of in vitro and in vivo studies on flow rate dependency were carried out.
METHODS
Inspiratory flow parameters via EH and Symbicort(®) Turbuhaler(®) (TH) inhalers were evaluated in 187 patients with asthma and COPD. The 10(th), 50(th), and 90(th) percentile flow rates achieved by patients were utilized to study in vitro flow rate dependency of budesonide/formoterol EH and Symbicort TH. In addition, an exploratory pharmacokinetic study on pulmonary deposition of active substances for budesonide/formoterol EH in healthy volunteers was performed.
RESULTS
Mean inspiratory flow rates through EH were 64 and 56 L/min in asthmatics and COPD patients, and through TH 79 and 72 L/min, respectively. Children with asthma had marginally lower PIF values than the adults. The inspiratory volumes were similar in all groups between the inhalers. Using weighted 10(th), 50(th), and 90(th) percentile flows the in vitro delivered doses (DDs) and fine particle doses (FPDs) for EH were rather independent of flow as 98% of the median flow DDs and 89%-93% of FPDs were delivered already at 10(th) percentile air flow. Using±15% limits, EH and TH had similar flow rate dependency profiles between 10(th) and 90(th) percentile flows. The pharmacokinetic study with budesonide/formoterol EH in healthy subjects (n=16) revealed a trend for a flow-dependent increase in lung deposition for both budesonide and formoterol.
CONCLUSIONS
Comparable in vitro flow rate dependency between budesonide/formoterol EH and Symbicort TH was found using the range of clinically relevant flow rates. The results of the pharmacokinetic study were in accordance with the in vitro results showing only a trend of flow rate-dependant increase in lung deposition of active substances with EH.
背景
Easyhaler（EH）装置计量干粉吸入器含有布地奈德和福莫特罗，正在开发用于哮喘和慢性阻塞性肺疾病（COPD）。作为产品优化的一部分，进行了一系列关于流速依赖性的体外和体内研究。
方法
评估了 187 名哮喘和 COPD 患者使用 EH 和 Symbicort（®）Turbuhaler（®）（TH）吸入器的吸气流量参数。利用患者达到的 10（th）、50（th）和 90（th）百分位数流量来研究布地奈德/福莫特罗 EH 和 Symbicort TH 的体外流速依赖性。此外，还在健康志愿者中进行了布地奈德/福莫特罗 EH 活性物质肺部沉积的探索性药代动力学研究。
结果
EH 在哮喘患者和 COPD 患者中的平均吸气流量分别为 64 和 56 L/min，TH 分别为 79 和 72 L/min。哮喘儿童的 PIF 值略低于成人。在所有组中，两种吸入器的吸气量相似。使用加权 10（th）、50（th）和 90（th）百分位数流量，EH 的体外输送剂量（DD）和细颗粒剂量（FPD）与流量相当独立，98%的中位数流量 DD 和 89%-93%的 FPD 已经在 10（th）%的空气流量下输送。使用±15%的限制，EH 和 TH 在 10（th）到 90（th）%的流量之间具有相似的流速依赖性。在健康受试者（n=16）中进行的布地奈德/福莫特罗 EH 的药代动力学研究显示，布地奈德和福莫特罗的肺部沉积呈流速依赖性增加的趋势。
结论
在使用临床相关流速范围内，发现布地奈德/福莫特罗 EH 和 Symbicort TH 之间具有相当的体外流速依赖性。药代动力学研究的结果与体外结果一致，仅显示 EH 中活性物质肺部沉积的流速依赖性增加趋势。
Zotero 插件