USE OF WHOLE-BODY PLETHYSMOGRAPHY TO COMPARE BRONCHODILATOR INHALER EFFICACY

Whole-body plethysmography is not included in guidelines from regulato ry authorities for the development of treatments or delivery devices f or lung disease, despite its potential advantages compared to spiromet ry, Two separate studies were undertaken to assess the use of specific airway conductance (sG(aw)) as a pharmacodynamic endpoint for the com parison of two bronchodilator delivery systems (a novel dry powder inh aler and a standard metered dose inhaler). The first pilot study invol ved delivery of a single dose of salbutamol (200 mu g) to 13 healthy v olunteers and determination of sG(aw) up to 120 min after treatment. T he second study involved delivery of cumulative doses of salbutamol (1 00, 200 and 400 mu g) to 19 healthy volunteers with demonstrated rever sibility of sG(aw) to the bronchodilator and measurement of sG(aw) up to 240 min after treatment. In both studies, increases in sG(aw) after treatment were significant compared to placebo and larger than the re corded increases in FEV1. Increases in sG(aw) were similar for both de livery devices and support the therapeutic equivalence of the two prod ucts. Power calculations indicated that the second study had appropria te statistical power to discriminate between treatments. It is conclud ed that the assessment of sG(aw) in healthy volunteers may be a useful and sensitive pharmacodynamic endpoint for use in the development of bronchodilators and their delivery devices.