Salmeterol inhaler using a non-chlorinated propellant, HFA134a: systemic pharmacodynamic activity in healthy volunteers.
BACKGROUND
Metered dose inhalers for the treatment of asthma use chlorofluorocarbons as propellants. These face an international ban due to their effect on the ozone layer. Salmeterol has been reformulated using the non-chlorinated propellant Glaxo inhalation grade HFA134a.


METHODS
The safety, tolerability and systemic pharmacodynamic activity of the salmeterol/HFA134a inhaler, the current salmeterol inhaler, and placebo (HFA134a) were compared in 12 healthy volunteers in a double blind, randomised crossover study using a cumulative dosing design.


RESULTS
Safety and tolerability were similar and the response was related to the dose over the range used (50-400 micrograms) with both salmeterol inhalers. The salmeterol/HFA134a inhaler showed no differences from the current inhaler for pulse rate, blood pressure, tremor, QTc interval, and plasma glucose levels. The salmeterol/HFA134a inhaler had significantly less effect on plasma potassium levels.


CONCLUSIONS
In healthy volunteers the salmeterol/HFA134a inhaler is at least as safe and well tolerated as the current salmeterol inhaler, and has similar systemic pharmacodynamic activity.
Kirby
S M
SM
Clinical Pharmacology Division, Glaxo Research and Development Ltd, Greenford, Middlesex, UK.
Smith
J
J
Ventresca
G P
GP
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000009:adverse effects / Q000493:pharmacokinetics*; D000328:Adult; D000335:Aerosol Propellants / Q000493:pharmacokinetics*; D000420:Albuterol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000493:pharmacokinetics*; D008297:Male; D011188:Potassium / Q000097:blood; D011674:Pulse / Q000187:drug effects; D000068299:Salmeterol Xinafoate; D004980:Ethane / Q000031:analogs & derivatives; D005466:Fluorocarbons
D000318:Adrenergic beta-Agonists; D000335:Aerosol Propellants; D000420:Albuterol; D001993:Bronchodilator Agents; D006845:Hydrocarbons, Fluorinated; D011188:Potassium; D000068299:Salmeterol Xinafoate; C063006:norflurane; D004980:Ethane; D005466:Fluorocarbons