Borgström L, Derom E, Ståhl E, Wåhlin-Boll E, Pauwels R
Astra Draco AB, Lund, Sweden.
Am J Respir Crit Care Med. 1996 May;153(5):1636-40. doi: 10.1164/ajrccm.153.5.8630614.
The development of new inhalation devices for asthma drugs raises the issue of the relationship between pulmonary deposition and therapeutic effect of inhaled drugs in patients with obstructive lung diseases. We thus conducted a randomized, double-blind and double-dummy, four-period crossover study in 13 patients with moderate asthma (mean age 36 yr; FEV1 59% of predicted), who inhaled 0.25 and 0.5 mg terbutaline sulphate on separate occasions either via a pressurized metered dose inhaler (pMDI) or Turbuhaler (TBH). Pulmonary deposition was 8.1 +/- 2.7% and 8.3 +/- 2.3%, respectively, of the nominal dose for pMDI and 19.0 +/- 7.3%, and 22.0 +/- 8.1% for TBH. The FEV1 increase after 0.25 mg terbutaline sulphate via TBH was significantly greater than after 0.25 mg via pMDI. No significant differences in FEV1 increase were observed between 0.25 mg via TBH, 0.5 mg via pMDI, or 0.5 mg via TBH. Other lung function variables showed similar dose- and device-related changes. We concluded that: (1) the dose of terbutaline sulphate deposited in the lungs is dependent on which inhalation system is used; (2) TBH delivers about twice the amount of drug to the lungs as the pMDI; and (3) the observed difference in deposition is reflected in the bronchodilating effect.
用于哮喘药物的新型吸入装置的研发引发了阻塞性肺病患者吸入药物的肺部沉积与治疗效果之间关系的问题。因此,我们对13例中度哮喘患者(平均年龄36岁;FEV1为预测值的59%)进行了一项随机、双盲、双模拟、四期交叉研究,这些患者分别通过压力定量吸入器(pMDI)或都保(TBH)吸入0.25毫克和0.5毫克硫酸特布他林。pMDI的肺部沉积分别为标称剂量的8.1±2.7%和8.3±2.3%,TBH的肺部沉积分别为19.0±7.3%和22.0±8.1%。通过TBH吸入0.25毫克硫酸特布他林后FEV1的增加显著大于通过pMDI吸入0.25毫克后的增加。在通过TBH吸入0.25毫克、通过pMDI吸入0.5毫克或通过TBH吸入0.5毫克之间,未观察到FEV1增加有显著差异。其他肺功能变量显示出类似的剂量和装置相关变化。我们得出结论:(1)肺部沉积的硫酸特布他林剂量取决于所使用的吸入系统;(2)TBH输送到肺部的药物量约为pMDI的两倍;(3)观察到的沉积差异反映在支气管扩张作用中。