Pharmacokinetics and dose proportionality of beclomethasone from three strengths of a CFC-free beclomethasone dipropionate metered-dose inhaler.
As part of a development program to offer alternatives to chlorofluorocarbon (CFC) containing metered-dose inhalers, beclomethasone dipropionate has been formulated in a CFC-free system at three strengths: 50, 100, and 200 micrograms/actuation ex valve. To measure serum levels and dose proportionality of the beclomethasone derived from beclomethasone dipropionate, 13 mild to moderate asthmatic patients received a single dose of eight inhalations from each strength according to a double-blind crossover design. Seven patients were studied over 4 h and six patients over 12 h. For the total doses of 400, 800, and 1600 micrograms studied over 12 h, Cmax and AUC increased in a ratio of 1:1.8:3.1. A good correlation was seen between the fine-particle mass delivered and the in vivo performance of the three strengths. From a clinical point of view, the predictable increases in serum levels with an increase in dose will permit the clinician to effectively titrate a patient with this product.
Harrison
L I
LI
3M Pharmaceuticals, 3M Center, St Paul, MN 55144, USA.
Dahl
D R
DR
Cline
A
A
Chang
S F
SF
Machacek
J
J
Nelson
J
J
Kannianinen
C
C
Purrington
A
A
D000280:Administration, Inhalation; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001249:Asthma / Q000097:blood / Q000188:drug therapy; D001507:Beclomethasone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D017402:Chlorofluorocarbons; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers / Q000592:standards*
D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D017402:Chlorofluorocarbons; D001507:Beclomethasone