PHARMACOKINETICS AND DOSE PROPORTIONALITY OF BECLOMETHASONE FROM 3 STRENGTHS OF A CFC-FREE BECLOMETHASONE DIPROPIONATE METERED-DOSE INHALER

As part of a development program to offer alternatives to chlorofluoro carbon (CFC) containing metered-dose inhalers, beclomethasone dipropio nate has been formulated in a CFC-free system at three strengths: 50, 100, and 200 mu g/actuation ex valve. To measure serum levels and dose proportionality of the beclomethasone derived from beclomethasone dip ropionate, 13 mild to moderate asthmatic patients received a single do se of eight inhalations from each strength according to a double-blind crossover design. Seven patients were studied over 4 h and six patien ts over 12 h. For the total doses of 400, 800, and 1600 mu g studied o ver 12 h, C-max and AUC increased in a ratio of 1:18:31. A good correl ation was seen between the fine-particle mass delivered and the in viv o performance of the three strengths. From a clinical point of view, t he predictable increases in serum levels with an increase in dose will permit the clinician to effectively titrate a patient with this produ ct. (C) 1997 by John Wiley & Sons, Ltd.