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) beclomethasone dipropionate (BDP) metered-dose inhaler (MDI) with the use of the propellant HFA-134a (HFA). Lung deposition studies demonstrated that the HFA BDP MDI delivers to the lungs approximately 56% of the BDP dose (ex-adaptor), a substantially higher percentage than the 5-30% delivered by conventional CFC BDP MDIs. As new sensitive bioanalytical methods are becoming available to quantitate systemic levels of inhaled corticosteroids, pharmacokinetic evaluations are emerging as sensitive and reproducible methods that can be used as a complement to the data obtained from lung deposition studies to assess and compare the performance of MDIs. The present study was designed to determine the beclomethasone (BOH) availability of oral BDP relative to inhaled HFA BDP as a first step to alloy 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 to inhaled HFA BDP. In addition, the fraction of an oral dose that reaches the systemic circulation was estimated from the 40% relative availability and previous lung deposition data to be 0.26. These estimated pharmacokinetic parameters will be used in the future to further characterize the pharmacokinetics of inhaled BDP and to compare the performance of different MDI products.
Department of Pharmacokinetics and Drug Metabolism, St. Paul, MN 55144-1000, USA. isoria1@mmm.com
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Soria
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Harrison
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Machacek
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Cline
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Stampone
D000280:Administration, Inhalation; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001507:Beclomethasone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers
D001507:Beclomethasone