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通过呼吸启动的压力气雾剂和干粉吸入器装置进行沙丁胺醇的肺部给药。

Lung delivery of salbutamol given by breath activated pressurized aerosol and dry powder inhaler devices.

作者信息

Lipworth B J, Clark D J

机构信息

Department of Clinical Pharmacology, Ninewells Hospital & Medical School, University of Dundee, Scotland, UK.

出版信息

Pulm Pharmacol Ther. 1997 Aug;10(4):211-4. doi: 10.1006/pupt.1997.0093.

Abstract

Poor inhalation technique is prevalent in asthmatics using standard metered dose inhalers (MDI). Both dry powder inhalers (DPI) and breath activated MDIs offer a solution to this problem. Our aim was to compare the lung delivery of salbutamol from two DPIs, Diskhaler and Diskus (Accuhaler), and the Easi-Breathe breath activated MDI. Ten healthy volunteers mean (SEM) age 24.0 years (1.7) were studied in a randomized single (investigator) blind crossover design. Single 1200 micrograms nominal doses of salbutamol via Diskhaler and Diskus (6 sequential 200 micrograms puffs) and Easi-Breathe (12 sequential 100 micrograms puffs) were given over 6 min. Mouth rinsing was performed after every inhalation sequence. Lung delivery was evaluated by measuring the early lung absorption profile of salbutamol at 5, 10, 15 and 20 min after inhalation, with calculation of peak (Cmax) and average over 20 min (Cav) concentration (ng/ml). Both the Diskhaler and the Easi-Breathe produced significantly greater salbutamol Cmax and Cav than Diskus (as mean and 96% CI for difference vs. Diskus): [Cmax] Diskus 3.22 vs. Diskhaler 4.35 (95% CI 0.19 to 2.08), vs. Easi-Breathe 3.98 (95% CI -0.18 to 1.71). [Cav] Diskus 2.62 vs. Diskhaler 3.95 (95% CI 0.52 to 2.14), vs. Easi-Breathe 3.52 (95% CI 0.09 to 1.71). For Cav this amounted to a 1.51-fold difference (95% CI 1.35 to 1.68) between Diskhaler vs. Diskus, and a 1.36-fold difference (95% CI 1.03 to 1.69) for Easi-Breathe vs. Diskus. In conclusion we found that, in vivo, the Diskus DPI produced significantly lower lung delivery for the same nominal dose of salbutamol than either Diskhaler DPI or the Easi-Breathe pressurised aerosol. This shows that breath activated inhaler devices may have different in vivo deposition characteristics for delivering the same drug.

摘要

在使用标准定量吸入器(MDI)的哮喘患者中,吸入技术不佳的情况很普遍。干粉吸入器(DPI)和呼吸启动型MDI都为解决这一问题提供了方案。我们的目的是比较两种DPI(Diskhaler和Diskus(准纳器))以及易呼吸呼吸启动型MDI的沙丁胺醇肺部递送情况。采用随机单(研究者)盲交叉设计,对10名健康志愿者进行了研究,他们的平均(标准误)年龄为24.0岁(1.7)。在6分钟内,通过Diskhaler和Diskus(6次连续200微克喷雾)以及易呼吸(12次连续100微克喷雾)给予单次1200微克标称剂量的沙丁胺醇。每次吸入序列后进行漱口。通过测量吸入后5、10、15和20分钟时沙丁胺醇的早期肺部吸收情况来评估肺部递送,并计算峰值(Cmax)和20分钟内的平均(Cav)浓度(纳克/毫升)。Diskhaler和易呼吸产生的沙丁胺醇Cmax和Cav均显著高于Diskus(差异的均值和96%置信区间与Diskus相比):[Cmax] Diskus为3.22,Diskhaler为4.35(95%置信区间0.19至2.08),易呼吸为3.98(95%置信区间 -0.18至1.71)。[Cav] Diskus为2.62,Diskhaler为3.95(95%置信区间0.52至2.14),易呼吸为3.52(95%置信区间0.09至1.71)。对于Cav,Diskhaler与Diskus之间的差异为1.51倍(95%置信区间1.35至1.68),易呼吸与Diskus之间的差异为1.36倍(95%置信区间1.03至1.69)。总之,我们发现,在体内,对于相同标称剂量的沙丁胺醇,Diskus DPI产生的肺部递送显著低于Diskhaler DPI或易呼吸压力气雾剂。这表明呼吸启动型吸入装置在递送相同药物时可能具有不同的体内沉积特征。

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