Pharmacokinetic and Pharmacodynamic Properties of Inhaled Beclometasone Dipropionate Delivered Via Hydrofluoroalkane-Containing Devices

Abstract

Inhaled corticosteroids have a key role in the treatment of asthma and chronic obstructive pulmonary disease. In recent times, beclometasone dipropionate has been reformulated in pressurised metered dose inhalers (pMDIs), using hydrofluoroalkanes (HFAs) as a propellant. Extensive toxicological testing has shown that HFA-propellants are well tolerated. Among the reformulated beclometasone dipropionate-containing pMDIs, only the characteristics of the two Qvar™ formulations have been thoroughly explored. Compared to the reference beclometasone dipropionate formulation, the mass median aerodynamic diameter of the Qvar™ formulations are substantially smaller (1.1 vs 4.0μm), whereas that of Modulite® averages 2.6μm. Scintigraphic and pharmacokinetic studies indicate a higher lung deposition for both the Qvar™ and the Beclazone® formulations, compared with reference beclometasone dipropionate formulation. Since the 2- to 3-fold increase in pulmonary deposition results in a 2.6- to 3-fold difference in relative efficacy for Qvar™, half the dose of the reference beclometasone dipropionate formulation has been currently recommended in adult patients with asthma, a recommendation that is supported by a large number of clinical trials. Conversely, the design of the studies conducted to compare the efficacy of Qvar™ with fluticasone propionate and budesonide does not allow establishing their equivalence on a milligram per milligram basis. Good studies on the bioequivalence between the reference beclometasone dipropionate formulation and the Modulite® or Beclazone® formulations are not available.