Is inhaled beclomethasone (BDP) with a non-CFC propellant equivalent to the CFC propellant formulations?

We read with interest the recent article of Milanowski et al. (1) which reported an apparent equivalent anti-asthmatic e€ect of low (400 mg per day) and high (2000 mg per day) doses of HFA-134a (Norton Healthcare Ltd, London, U.K.) and CFC formulations of beclomethasone dipropionate (BDP). In order to evaluate the relative potency of two inhaled corticosteroid formulations, it is necessary to compare anti-asthmatic e€ects on the steep part of the dose-response curve, preferably using at least three doses (2). In the study of Milanowski et al. baseline values for mean forced expiratory volume in 1 sec (FEV1) showed that both groups were well matched for the low dose study (67% predicted) and the high dose study (70% predicted). The primary ecacy variable from the intent-to-treat populations showed no evidence of a dose-response e€ect between 2000 mg per day and 400 mg per day for either the CFC or HFA formulations, in terms of the change in FEV1 between baseline and end-point after 6 weeks of treatment. For HFA-BDP the mean change in FEV1 was 0 4 l at 400 mg and 0 2 l for 2000 mg, whilst for CFC-BDP values were 0 3 l and 0 3 l, respectively. In other words, for the patients who were studied, 400 mg day of either CFC or HFA-BDP was on the plateau part of the dose-response curve. Hence it is not possible to make any valid conclusions regarding therapeutic equivalence from these data. Had the authors evaluated doses of BDP less than 400 mg per day on the steep part of the dose-response curve, it is conceivable that di€erences in anti-asthmatic potency between the two formulations may have become evident. In this respect we have recently performed a pharmacokinetic study to compare the systematic bioequivalence of a 1000 mg nominal dose of HFA-134a BDP metered dose inhaler (as Beclazone-CFC free 250 mg per actuation, Norton-Waterford, Ireland) or CFC containing metered dose inhaler (Beclazone 250 mg per actuation) (3). The HFA-134a BDP inhaler was identical to that used in the study of Milanowski et al. Plasma levels of beclomethasone-17-monopropionate (17-BMP) were measured over a 12 h period after inhalation. The results showed mean values for the area under the curve (AUC0±12) were 1 5 fold greater, and mean values for maximum plasma concentration (Cmax) were 1 9 fold greater when comparing HFABDP vs. CFC-BDP formulations. Furthermore, the 90% con®dence interval for the ratio of HFA-BDP to CFC-BDP was outside of that established for bioequivalence for both AUC (90% CI 1 33±1 95) and Cmax (90% CI 1 57±2 61).