Pharmacokinetics of chlorofluorocarbon and hydrofluoroalkane metered-dose inhaler formulations of beclomethasone dipropionate

Authors


Professor Brian J Lipworth Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, UK. Tel.: +44 1382 632 983, Fax: +44 1382 644 972, E-mail: b.j.lipworth@dundee.ac.uk

Abstract

Aims To compare the pharmacokinetic profile of BeclazoneTM (beclomethasone dipropionate) in its chlorofluorocarbon (CFC)-based and CFC-free formulations.

Methods Ten healthy adults received a single 1000 μg nominal dose (ex-valve) of beclomethasone dipropionate from a CFC inhaler (BEC-CFC) or from a CFC-free inhaler containing hydrofluoroalkane (HFA)-134a (BEC-HFA) in an open-label, randomized, two-way, crossover study. Blood samples were collected predose and over 12 h after inhalation. Comparisons were made of maximum plasma concentration of beclomethasone 17-monopropionate (17-BMP) (Cmax ), and area under the plasma concentration vs time curve (AUC).

Results The tmax was significantly (P<0.05) earlier with BEC-HFA and plasma levels were significantly higher following administration of BEC-HFA than BEC-CFC. Geometric mean values for AUC were 1.5 fold greater (90% CI 1.3–1.9) and for Cmax were 1.9 fold greater (90% CI 1.6–2.6) following BEC-HFA than BEC-CFC.

Conclusions Our data in healthy volunteers would not be consistent with the manufacturers’ recommendation for a microgram equivalent (1:1) nominal dose switch between these HFA and CFC formulations. Further well designed trials are required in asthmatic patients to properly define their respective dose–response relationships for antiasthmatic and systemic adverse effects.

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