Morice A H, Waterhouse J C, Peers E M, Parry-Billings M
Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield, UK.
Respiration. 1998;65(2):120-4. doi: 10.1159/000029242.
Whole-body plethysmography is not included in guidelines from regulatory authorities for the development of treatments or delivery devices for lung disease, despite its potential advantages compared to spirometry. Two separate studies were undertaken to assess the use of specific airway conductance (sGaw) as a pharmacodynamic endpoint for the comparison of two bronchodilator delivery systems (a novel dry powder inhaler and a standard metered dose inhaler). The first pilot study involved delivery of a single dose of salbutamol (200 micrograms) to 12 healthy volunteers and determination of sGaw up to 120 min after treatment. The second study involved delivery of cumulative doses of salbutamol (100, 200 and 400 micrograms) to 19 healthy volunteers with demonstrated reversibility of sGaw to the bronchodilator and measurement of sGaw up to 240 min after treatment. In both studies, increases in sGaw after treatment were significant compared to placebo and larger than the recorded increases in FEV1. Increases in sGaw were similar for both delivery devices and support the therapeutic equivalence of the two products. Power calculations indicated that the second study had appropriate statistical power to discriminate between treatments. It is concluded that the assessment of sGaw in healthy volunteers may be a useful and sensitive pharmacodynamic endpoint for use in the development of bronchodilators and their delivery devices.
尽管与肺活量测定法相比，全身体积描记法具有潜在优势，但监管机构制定的肺部疾病治疗方法或给药装置的指南中并未将其纳入。开展了两项独立研究，以评估将比气道传导率（sGaw）作为药效学终点，用于比较两种支气管扩张剂给药系统（一种新型干粉吸入器和一种标准定量吸入器）的情况。第一项初步研究包括向12名健康志愿者单次给药沙丁胺醇（200微克），并在治疗后长达120分钟测定sGaw。第二项研究包括向19名sGaw对支气管扩张剂有可逆性表现的健康志愿者累积给药沙丁胺醇（100、200和400微克），并在治疗后长达240分钟测量sGaw。在两项研究中，与安慰剂相比，治疗后sGaw的增加均具有显著性，且大于记录的第一秒用力呼气容积（FEV1）的增加。两种给药装置的sGaw增加相似，支持了两种产品的治疗等效性。功效计算表明，第二项研究具有适当的统计功效来区分不同治疗方法。得出的结论是，在健康志愿者中评估sGaw可能是用于支气管扩张剂及其给药装置研发的一种有用且敏感的药效学终点。
