Pharmacokinetic and pharmacodynamic properties of inhaled beclometasone dipropionate delivered via hydrofluoroalkane-containing devices.
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 4.0 microm), whereas that of Modulite averages 2.6 microm. 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.
Derom
Eric
E
Department of Respiratory Diseases, Ghent University Hospital, De pintelaan 185, B-9000 Gent, Belgium. eric.derom@Ugent.be
Pauwels
Romain A
RA
D000280:Administration, Inhalation; D000335:Aerosol Propellants; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy; D001507:Beclomethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D005938:Glucocorticoids / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D006845:Hydrocarbons, Fluorinated; D013810:Therapeutic Equivalency; D005466:Fluorocarbons
D000335:Aerosol Propellants; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D001507:Beclomethasone; D005938:Glucocorticoids; D006845:Hydrocarbons, Fluorinated; C094049:apaflurane; D005466:Fluorocarbons