RELATIVE BIOAVAILABILITY OF SALBUTAMOL TO THE LUNG FOLLOWING INHALATION USING METERED-DOSE INHALATION METHODS AND SPACER DEVICES

Background - Inhalation aids do not require coordination between actua tion of a metered dose inhaler (MDI) with inspiration and reduce oroph aryngeal impaction. The delivery of sarbutamol to the lung and systemi c availability following inhalation with three commonly used spacers a nd an open mouth technique have been evaluated using a simple noninvas ive technique based on urinary excretion 30 minutes and 24 hours after the dose. Methods - Ten healthy subjects inhaled, on randomised study days, 4 x 100 mu g from a Ventolin MDI and, subsequently, with the ai d of a Volumatic, Bricanyl Spacer, and Nebuhaler spacer device. In add ition, an open mouth inhaler technique was evaluated, Urine samples we re collected 0-30 minutes and 0.5-24 hours after inhalation. From thes e samples the relative bioavailability to the lung (urinary salbutamol excretion 30 minutes after dosing) and the systemic bioavailability o f the dose (24 hour urinary excretion of salbutamol and its metabolite ) for each inhalation method was obtained. Results - The mean (SD) uri nary excretion of salbutamol 30 minutes after inhalation using the MDI alone and with the Volumatic, Bricanyl Spacer, Nebuhaler, and open mo uth technique was 2.83 (0.78)%, 3.37 (0.69)%, 4.09 (0.91)%, 4.34 (1.60 )%, and 3.49 (0.98)%, respectively, expressed as a percentage of the n ominal dose. The Nebuhaler and Bricanyl Spacer spacer devices were fou nd to increase the relative bioavailability of salbutamol to the lung compared with the MDI alone. Compared with the MDI the inhalation aid increases were much greater than the intra-individual variability of t he urinary excretion method, In 11 individuals who each repeated the s ame inhalation procedure on four separate occasions, the mean (SD) coe fficient of variation was 8.24 (2.36)%. The mean (SD) 24 hour urinary excretion of salbutamol and its metabolites was 26.6 (6.79), 27.0 (7.9 5), and 55.6 (9.74)% of the salbutamol dose for the Volumatic, Nebuhal er, and MDI, respectively. Similar values following the open mouth met hod and Bricanyl Spacer were 48.9(10.97)% and 43.8 (11.57)%. These val ues, representing the systemic availability of the inhaled dose, were lower when inhaling with the aid of the Volumatic and Nebuhaler than i nhalation from the MDI alone. Conclusions - Spacer devices improve pul monary bioavailability of salbutamol and reduce the systemically avail able dose.