Clark D J, Lipworth B J
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, UK.
Thorax. 1996 Oct;51(10):981-4. doi: 10.1136/thx.51.10.981.
The aim of this study was to extend previous in vitro observations regarding the effects of multiple actuations of aerosols into spacer devices, delayed inhalation, and antistatic treatment of spacer devices on the amount of drug delivered for inhalation. An in vivo study of lung bioavailability of salbutamol from a large volume (Volumatic) spacer was conducted.
Ten healthy volunteers of mean age 20.5 years with a mean forced expiratory volume in one second of 112.1% predicted were studied in a randomised single blind (investigator blind) crossover study. 1200 micrograms of salbutamol was given with mouth rinsing (100 micrograms/puff) on four study days: single puffs via spacer, multiple puffs via spacer (3 x 4 puffs), single puffs with 20 second delay before inhalation via spacer, and single puffs via an antistatic treated spacer. All spacers, including those treated with antistatic, were prewashed prior to each study day. Measurements of lung bioavailability were made at five, 10, and 20 minutes after inhalation to determine peak (Cmax) and average (Cav) plasma salbutamol levels. Systemic beta 2 responses including finger tremor, heart rate, and plasma potassium levels were also evaluated.
Single puffs from the spacer produced higher plasma salbutamol levels and greater systemic beta 2 responses than either multiple puffs or single puffs with delayed inhalation for a 1200 micrograms dose. For Cmax this amounted to a 1.93-fold (95% CI 1.68 to 2.19) greater lung bioavailability for single puffs than for multiple puffs and a 1.80-fold (95% CI 1.59 to 2.00) greater lung bioavailability for single puffs than for single puffs with a 20 second delay. Comparison of the normal and antistatic treated spacers (both prewashed) revealed differences for Cmax with levels 1.23-fold (95% CI 1.04 to 1.41) greater for the normal spacer.
Delayed inhalation from a Volumatic spacer and the use of multiple puffs results in a considerable decrease in the delivery of salbutamol to the lungs with an approximate twofold reduction in lung bioavailability. Washing a Volumatic spacer is as effective as an antistatic lining in reducing the effects of static charge on salbutamol delivery in vivo.
本研究的目的是扩展先前关于多次向储雾罐装置喷射气雾剂、延迟吸入以及对储雾罐装置进行抗静电处理对吸入药物递送量影响的体外观察结果。开展了一项关于大剂量储雾罐（Volumatic）中沙丁胺醇肺生物利用度的体内研究。
在一项随机单盲（研究者盲法）交叉研究中，对10名平均年龄20.5岁、一秒用力呼气量平均为预测值112.1%的健康志愿者进行了研究。在四个研究日，每次口含漱后给予1200微克沙丁胺醇（100微克/喷）：通过储雾罐单次喷入、通过储雾罐多次喷入（3×4喷）、通过储雾罐吸入前延迟20秒单次喷入以及通过抗静电处理的储雾罐单次喷入。所有储雾罐，包括经过抗静电处理的，在每个研究日前均预先清洗。在吸入后5分钟、10分钟和20分钟测量肺生物利用度，以确定血浆沙丁胺醇的峰值（Cmax）和平均（Cav）水平。还评估了包括手指震颤、心率和血浆钾水平在内的全身β2反应。
对于1200微克剂量，与多次喷入或延迟吸入的单次喷入相比，储雾罐单次喷入产生更高的血浆沙丁胺醇水平和更强的全身β2反应。对于Cmax，单次喷入的肺生物利用度比多次喷入高1.93倍（95%可信区间1.68至2.19），比延迟20秒的单次喷入高1.80倍（95%可信区间1.59至2.00）。比较正常储雾罐和抗静电处理的储雾罐（均预先清洗）发现，Cmax存在差异，正常储雾罐的水平高1.23倍（95%可信区间1.04至1.41）。
从Volumatic储雾罐延迟吸入和多次喷入会导致沙丁胺醇向肺部的递送量显著降低，肺生物利用度降低约两倍。清洗Volumatic储雾罐在减少静电荷对体内沙丁胺醇递送的影响方面与抗静电内衬同样有效。
