Pharmacokinetics of chlorofluorocarbon and hydrofluoroalkane metered-dose inhaler formulations of beclomethasone dipropionate.
OBJECTIVE
To compare the pharmacokinetic profile of Beclazone (beclomethasone dipropionate) in its chlorofluorocarbon (CFC)-based and CFC-free formulations.


METHODS
Ten healthy adults received a single 1,000 microg nominal dose (ex-valve) of beclomethasone dipropionate from a CFC inhaler (BEC-CFC) or from a CFC-free inhaler containing hydrofluoroalkane (HFA)-134a (BEC-HFA) in an open-label, randomized, two-way, crossover study. Blood samples were collected predose and over 12 h after inhalation. Comparisons were made of maximum plasma concentration of beclomethasone 17-monopropionate (17-BMP) (Cmax), and area under the plasma concentration vs time curve (AUC).


RESULTS
The tmax was significantly (P<0.05) earlier with BEC-HFA and plasma levels were significantly higher following administration of BEC-HFA than BEC-CFC. Geometric mean values for AUC were 1.5 fold greater (90% CI 1.3-1.9) and for Cmax were 1.9 fold greater (90% CI 1.6-2.6) following BEC-HFA than BEC-CFC.


CONCLUSIONS
Our data in healthy volunteers would not be consistent with the manufacturers' recommendation for a microgram equivalent (1:1) nominal dose switch between these HFA and CFC formulations. Further well designed trials are required in asthmatic patients to properly define their respective dose-response relationships for antiasthmatic and systemic adverse effects.
Lipworth
B J
BJ
Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee, Scotland, UK. b.j.lipworth@dundee.ac.uk
Jackson
C M
CM
D000328:Adult; D000335:Aerosol Propellants; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001507:Beclomethasone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D017402:Chlorofluorocarbons; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D006845:Hydrocarbons, Fluorinated; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D005466:Fluorocarbons
D000335:Aerosol Propellants; D000893:Anti-Inflammatory Agents; D001507:Beclomethasone; D017402:Chlorofluorocarbons; D006845:Hydrocarbons, Fluorinated; C094049:apaflurane; D005466:Fluorocarbons