B J Lipworth1, D J Clark. 1. Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital & Medical School, University of Dundee.
Abstract
AIMS: To compare the lung delivery of salbutamol from a commonly used constant output open vent jet nebuliser (Sidestream) with use of both a conventional large volume plastic spacer (Volumatic) and a novel small volume metal spacer (NebuChamber). This was assessed using the early lung absorption profile of salbutamol over the first 20 min after inhalation. METHODS:Twelve healthy volunteers were studied in a randomized single (investigator) blind crossover design. Single 1200 microg nominal doses salbutamol from a CFC-free metered-dose inhaler (12 sequential 100 microg puffs of Airomir) were delivered via the Volumatic and NebuChamber spacers. A single 1200 microg nominal dose of salbutamol was given as a 4 ml fill volume from a Sidestream nebuliser with mouthpiece. Mouth rinsing was performed after each drug sequence. Plasma salbutamol was measured at 5, 10, 15 and 20 min after the last dose of each inhalation sequence, with calculation of maximal concentration (Cmax) and average concentration over 20 min (C[av]). Systemic beta2-responses were measured as plasma potassium, tremor and heart rate. RESULTS: Both the Volumatic and the NebuChamber spacers produced significantly greater salbutamol concentration than the Sidestream nebuliser. For C(av) this amounted to a 7.34-fold difference (95%CI 5.31 to 9.38) between Volumatic vs Sidestream, and a 7.04-fold difference (95%CI 4.91 to 9.17) for NebuChamber vs Sidestream. Similar differences were found for the extrapulmonary beta2-responses. There were no significant differences in either salbutamol concentration or extrapulmonary beta2-responses between the Volumatic and NebuChamber spacers. CONCLUSIONS: We found that, in vivo, both the Volumatic and the NebuChamber spacers produced seven-fold greater lung delivery of salbutamol than the Sidestream nebuliser when comparing microgram equivalent nominal doses, in terms of the early lung absorption profile.
RCT Entities:
AIMS: To compare the lung delivery of salbutamol from a commonly used constant output open vent jet nebuliser (Sidestream) with use of both a conventional large volume plastic spacer (Volumatic) and a novel small volume metal spacer (NebuChamber). This was assessed using the early lung absorption profile of salbutamol over the first 20 min after inhalation. METHODS: Twelve healthy volunteers were studied in a randomized single (investigator) blind crossover design. Single 1200 microg nominal doses salbutamol from a CFC-free metered-dose inhaler (12 sequential 100 microg puffs of Airomir) were delivered via the Volumatic and NebuChamber spacers. A single 1200 microg nominal dose of salbutamol was given as a 4 ml fill volume from a Sidestream nebuliser with mouthpiece. Mouth rinsing was performed after each drug sequence. Plasma salbutamol was measured at 5, 10, 15 and 20 min after the last dose of each inhalation sequence, with calculation of maximal concentration (Cmax) and average concentration over 20 min (C[av]). Systemic beta2-responses were measured as plasma potassium, tremor and heart rate. RESULTS: Both the Volumatic and the NebuChamber spacers produced significantly greater salbutamol concentration than the Sidestream nebuliser. For C(av) this amounted to a 7.34-fold difference (95%CI 5.31 to 9.38) between Volumatic vs Sidestream, and a 7.04-fold difference (95%CI 4.91 to 9.17) for NebuChamber vs Sidestream. Similar differences were found for the extrapulmonary beta2-responses. There were no significant differences in either salbutamol concentration or extrapulmonary beta2-responses between the Volumatic and NebuChamber spacers. CONCLUSIONS: We found that, in vivo, both the Volumatic and the NebuChamber spacers produced seven-fold greater lung delivery of salbutamol than the Sidestream nebuliser when comparing microgram equivalent nominal doses, in terms of the early lung absorption profile.
Authors: B J Lipworth; R A Clark; D P Dhillon; T A Moreland; A D Struthers; G A Clark; D G McDevitt Journal: Eur J Clin Pharmacol Date: 1989 Impact factor: 2.953