Pharmacokinetics and dose proportionality of beclomethasone from three strengths of a CFC-free beclomethasone dipropionate metered-dose inhaler

Abstract

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 μg/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 μg 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. © 1997 John Wiley & Sons, Ltd.

Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFC-beclomethasone

“…Thus, it would be expected that a given dose of drug from HFA-BDP would result in approximately 2.6-fold more drug in the serum than a similar dose of CFC-BDP. This approximate 2.6 factor has been confirmed in clinical pharmacokinetic studies [25], where all analytes of BDP were hydrolysed to free beclomethasone and subsequently analysed. In addition, clinical efficacy studies have confirmed that HFA-BDP has similar efficacy to approximately twice the dose of CFC-BDP [26,27].…”

The Influence of Lung Deposition on Clinical Response

“…exposure from the HFA MDI was more than twice that from the CFC MDI, (18,19) confirming the greater lung deposition from the HFA MDI.…”

Beclomethasone dipropionate: absolute bioavailability, pharmacokinetics and metabolism following intravenous, oral, intranasal and inhaled administration in man

“…Therefore, considering the other factors that can contribute to the variability in a particular study, such as type of study subject (patients or healthy subjects), inhaler technique, dose regimen and assay methodology, the value obtained seems to be a reasonable estimate. Previous attempts to assess the lung deposition of BDP from an MDI used a combination of gamma scintigraphy with 99m Tc‐labelled BDP formulations and pharmacokinetic data derived from a nonspecific assay method that measured total BOH in plasma after the hydrolysis of the plasma samples [16–18]. A nonuniform 99m Tc labelling of the BDP particles and presystemic metabolism of BDP probably account for the low estimate (5%) of BDP lung deposition by this method [17].…”

“…Previous studies have assessed the pharmacokinetics of BDP in terms of total BOH. This was done to simplify the methodology, and was achieved by the hydrolysis of BDP and its metabolites to BOH in the plasma samples prior to analysis [13, 16, 18]. For comparative purposes, we calculated the total BOH AUC for our data by converting the BDP, B‐17‐MP and BOH AUC values to BOH equivalents and summing them.…”