title: Effect of multiple actuations, delayed inhalation and antistatic treatment on the lung bioavailability of salbutamol via a spacer device.
abstract: BACKGROUND
  The aim of this study was to extend previous in vitro observations regarding the effects of multiple actuations of aerosols into spacer devices, delayed inhalation, and antistatic treatment of spacer devices on the amount of drug delivered for inhalation. An in vivo study of lung bioavailability of salbutamol from a large volume (Volumatic) spacer was conducted.
  
  
  METHODS
  Ten healthy volunteers of mean age 20.5 years with a mean forced expiratory volume in one second of 112.1% predicted were studied in a randomised single blind (investigator blind) crossover study. 1200 micrograms of salbutamol was given with mouth rinsing (100 micrograms/puff) on four study days: single puffs via spacer, multiple puffs via spacer (3 x 4 puffs), single puffs with 20 second delay before inhalation via spacer, and single puffs via an antistatic treated spacer. All spacers, including those treated with antistatic, were prewashed prior to each study day. Measurements of lung bioavailability were made at five, 10, and 20 minutes after inhalation to determine peak (Cmax) and average (Cav) plasma salbutamol levels. Systemic beta 2 responses including finger tremor, heart rate, and plasma potassium levels were also evaluated.
  
  
  RESULTS
  Single puffs from the spacer produced higher plasma salbutamol levels and greater systemic beta 2 responses than either multiple puffs or single puffs with delayed inhalation for a 1200 micrograms dose. For Cmax this amounted to a 1.93-fold (95% CI 1.68 to 2.19) greater lung bioavailability for single puffs than for multiple puffs and a 1.80-fold (95% CI 1.59 to 2.00) greater lung bioavailability for single puffs than for single puffs with a 20 second delay. Comparison of the normal and antistatic treated spacers (both prewashed) revealed differences for Cmax with levels 1.23-fold (95% CI 1.04 to 1.41) greater for the normal spacer.
  
  
  CONCLUSIONS
  Delayed inhalation from a Volumatic spacer and the use of multiple puffs results in a considerable decrease in the delivery of salbutamol to the lungs with an approximate twofold reduction in lung bioavailability. Washing a Volumatic spacer is as effective as an antistatic lining in reducing the effects of static charge on salbutamol delivery in vivo.
authors.affiliation: Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Clark
authors.forename: B J
authors.initials: BJ
authors.lastname: Lipworth
mesh_terms: D000328:Adult; D000420:Albuterol / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D001993:Bronchodilator Agents / Q000493:pharmacokinetics*; D004867:Equipment Design; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000378:metabolism; D009330:Nebulizers and Vaporizers; D011188:Potassium / Q000097:blood; D011897:Random Allocation; D016037:Single-Blind Method; D013997:Time Factors
chemical_list: D001993:Bronchodilator Agents; D000420:Albuterol; D011188:Potassium