title: Comparison of the systemic pharmacodynamic effects and pharmacokinetics of salmeterol delivered by CFC propellant and non-CFC propellant metered dose inhalers in healthy subjects.
abstract: This was a randomised, double-blind, placebo-controlled, cross-over study comparing the systemic pharmacodynamic effects (heart rate and serum potassium) and pharmacokinetics of salmeterol delivered by the non-CFC hydrofluoralkane (HFA) propellant 134a and the CFC propellant (propellant 11/12) metered dose inhalers (MDI) in healthy subjects. At the therapeutic dose (50 microg), salmeterol-mediated systemic pharmacodynamics were equivalent for the HFA and CFC MDIs. Higher doses of salmeterol (150 and 300 microg) produced dose-related beta-agonist pharmacodynamic effects irrespective of the propellant. However, these effects were lower with salmeterol HFA MDI than with the salmeterol CFC MDI at all dose levels. Overall, salmeterol Cmax and AUC(0-t) values were lower for salmeterol HFA compared with salmeterol CFC MDI. At the highest dose (300 microg), where a full pharmacokinetic profile was obtained, exposure to salmeterol delivered by the HFA MDI compared with the salmeterol CFC MDI was 27% and 30% lower for Cmax and AUC(0-t), respectively. Maximum plasma concentrations were generally seen in the first plasma samples taken 5 min after the start of dosing. Salmeterol HFA was well-tolerated. At supratherapeutic doses, adverse events were typical for high-dose salmeterol with fewer adverse events occurring with the HFA compared with the CFC formulation. These data indicate that the salmeterol HFA MDI would not be associated with a significantly different pharmacodynamic, safety and tolerability profile compared with the salmeterol CFC MDI.
authors.affiliation: Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline Research and Development, Greenford Road, Greenford, Middlesex UB6 0HE, UK. rodger.d.kempsford@gsk.com
authors.forename: Rodger
authors.initials: R
authors.lastname: Kempsford
authors.forename: Malcolm
authors.initials: M
authors.lastname: Handel
authors.forename: Rashmi
authors.initials: R
authors.lastname: Mehta
authors.forename: Mariza
authors.initials: M
authors.lastname: De Silva
authors.forename: Peter
authors.initials: P
authors.lastname: Daley-Yates
mesh_terms: D000293:Adolescent; D000328:Adult; D000335:Aerosol Propellants; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D001249:Asthma / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D017402:Chlorofluorocarbons; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006845:Hydrocarbons, Fluorinated; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D011188:Potassium / Q000097:blood; D000068299:Salmeterol Xinafoate; D005466:Fluorocarbons
chemical_list: D000335:Aerosol Propellants; D000420:Albuterol; D018927:Anti-Asthmatic Agents; D017402:Chlorofluorocarbons; D006845:Hydrocarbons, Fluorinated; D011188:Potassium; D000068299:Salmeterol Xinafoate; C094049:apaflurane; D005466:Fluorocarbons