Comparative in vivo lung delivery of hydrofluoroalkane-salbutamol formulation via metered-dose inhaler alone, with plastic spacer, or with cardboard tube.
OBJECTIVE
To compare the lung delivery of chlorofluorocarbon-free salbutamol via a pressurized metered-dose inhaler (pMDI) alone, a pMDI with a small-volume plastic spacer, and a pMDI with a cardboard tube.


METHODS
A randomized, single (investigator)-blind, three-way, crossover study.


METHODS
The Asthma and Allergy Research Group, Ninewells Hospital, University of Dundee, Dundee, Scotland, UK.


METHODS
Twelve healthy volunteers aged 16 to 65 years.


METHODS
The subjects were administered 400 microg of salbutamol via a pMDI alone, via a pMDI plus a small-volume plastic spacer, or via a pMDI plus a cardboard tube.


RESULTS
Blood samples for plasma salbutamol concentrations were taken at 5 min, 10 min, and 20 min after inhalation, to measure lung bioavailability as a surrogate for relative lung dose. The addition of the plastic spacer resulted in a significantly higher maximal plasma salbutamol concentration (CMAX) and average plasma salbutamol concentration (CAV) than the pMDI used alone. This amounted to a 1.48-fold (32%) difference (95% confidence interval [CI], 1.03 to 2.13) for CMAX and a 1.42-fold (30%) difference (95% CI, 1.01 to 2.00) for CAV. There was no significant difference in the CMAX or CAV comparing the addition of the cardboard tube with the plastic spacer or the pMDI alone.


CONCLUSIONS
Using a chlorofluorocarbon-free pMDI with a plastic spacer produced statistically, but not biologically, significant greater lung delivery of salbutamol. If a spacer is required for reasons other than increasing delivered drug dose, then the addition of a readily available cardboard tube will fulfill many of the required functions with no expense to the patient.
Fowler
S J
SJ
Asthma and Allergy Research Group, Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, UK.
Wilson
A M
AM
Griffiths
E A
EA
Lipworth
B J
BJ
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000335:Aerosol Propellants; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004867:Equipment Design; D006801:Humans; D006845:Hydrocarbons, Fluorinated; D008168:Lung / Q000378:metabolism*; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D016037:Single-Blind Method; D005466:Fluorocarbons
D000335:Aerosol Propellants; D000420:Albuterol; D001993:Bronchodilator Agents; D006845:Hydrocarbons, Fluorinated; C094049:apaflurane; D005466:Fluorocarbons