BECLOMETHASONE RELATIVE AVAILABILITY OF ORAL VERSUS INHALED BECLOMETHASONE DIPROPIONATE FROM AN HFA-134A METERED-DOSE INHALER

3M has formulated a new chlorofluorocarbon-free (CFC-free) beclomethas one dipropionate (BDP) metered-dose inhaler (MDI) with the use of the propellant HFA-134a (HFA). Lung deposition studies demonstrated that t he HFA BDP MDI delivers to the lungs approximately 56% of the BDP dose (ex-adaptor), a substantially higher percentage than the 5-30% delive red by conventional CFC BDP MDIs. As new sensitive bioanalytical metho ds are becoming available to quantitate systemic levels of inhaled cor ticosteroids, pharmacokinetic evaluations are emerging as sensitive an d reproducible methods that can be used as a complement to the data ob tained from lung deposition studies to assess and compare the performa nce of MDIs. The present study was designed to determine the beclometh asone (BOH) availability of oral BDP relative to inhaled HFA BDP as a first step to alley MDI product comparisons in the future. Forty mild asthmatic patients completed this open-label, randomized, single-dose, two-period crossover study. Each patient received an oral dose of BDP (0.2, 0.5, 1, 2 or 5 mg) in one period and an inhaled dose of BDP (0. 2 or 0.8 mg) in the other period, with four patients allocated to each of ten different treatment sequences. The BOH availability of orally administered BDP was approximately 40% relative Co inhaled HFA BDP. In addition, the fraction of an oral dose that reaches the systemic circ ulation was estimated from the 40% relative availability and previous lung deposition data to be 0.26. These estimated pharmacokinetic param eters will be used in the future to further characterize the pharmacok inetics of inhaled BDP and to compare the performance of different MDI products. (C) 1998 John Wiley & Sons, Ltd.