The relative bioavailability of salbutamol to the lung using urinary excretion following inhalation from a novel dry powder inhaler: the effect of inhalation rate and formulation

Each dry powder inhaler has a different resistance so that a respirable dose can be generated from the formulation by the patient's inspiratory effort. It is important to recognize that this effect is achievable. The inspiratory flow characteristics of asthmatics inhaling through a Clickhaler(R) were determined. In a separate study 10 volunteers inhaled separate 2x100 mu g salbutamol doses from a Clickhaler (ML Laboratories pie U.K.). Two different formulations tone with a high and one with a low respirable fraction) were each inhaled using an inspiratory flow of 30 and 60 l min(-1). A urine sample was collected 30 min post inhalation and then pooled for the next 24 h. The mean (SD) inhalation rate of 24 asthmatics when they inhaled from a Clickhaler was 37.3 (14.6) l min(-1). The mean (SD) urinary salbutamol excretion during the first 30 min, by the volunteers, using the high respirable dose formulation at 30 and 60 l min(-1) was 5.59 (1.87) and 4.62 (1.49) mu g respectively (P < 0.01). Similar values using the low respirable dose formulation were 4.84 (1.58) and 3.86 (2.14) mu g. There was no significant difference between the amounts excreted in the 24 h post-dose. The different 30-min urinary excretions following inhalation of the two formulations suggest a link between the relative bioavailability of salbutamol to the lung and the respirable dose, and that a slow inhalation rate should be used when using a Clickhaler. The patient study shows that this rate is achieved by most asthmatics without further training. (C) 2000 HARCOURT PUBLISHERS LTD.