Abstract
Background
Beclomethasone dipropionate (BDP) is an anti-inflammatory corticosteroid that is rapidly
metabolized to the pharmacologically active monoester, beclomethasone-17-monopropionate
(17-BMP). Recently, a hydrofluoroalkane (HFA)–propelled nasal aerosol formulation
of BDP was developed to treat allergic rhinitis. However, the pharmacokinetic profile
of BDP HFA nasal aerosol has not been previously investigated.
Objective
This study evaluated and compared the systemic levels of 17-BMP and BDP after a single
dose of intranasally administered or orally inhaled BDP HFA in healthy subjects.
Methods
In this single-center, randomized, open-label, 3-period crossover study, healthy subjects
received single doses of intranasal BDP HFA (80 and 320 μg) and orally inhaled BDP
HFA (320 μg). The primary pharmacokinetic parameters assessed were area under the
concentration-time curve until the last measurable value (AUClast) and Cmax for 17-BMP. For AUClast and Cmax, point estimates for treatment differences and CIs were calculated on the log scale
and then exponentiated to provide estimates of the geometric mean ratios (GMRs) and
associated CIs.
Results
Thirty subjects were randomized to receive study medication (aged 18–45 years, 66.7%
male). Mean plasma concentrations of 17-BMP after intranasal administration of BDP
HFA (for both 80- and 320-μg doses) were substantially lower than that of orally inhaled
BDP HFA (320 μg) across all time points. Mean AUClast values of 17-BMP for intranasal 80 μg, intranasal 320 μg, and orally inhaled 320
μg were 295.8, 1139.7, and 4140.3 pg·hr/mL, respectively. Mean Cmax values were 92.1, 262.7, and 1343.7 pg/mL, respectively. The GMR of AUClast for 17-BMP with intranasal BDP HFA 320 μg versus orally inhaled BDP HFA 320 μg was
0.275, indicating substantially lower systemic bioavailability with intranasal administration
than with oral inhalation. Similarly, the GMR of AUClast for 17-BMP with intranasal BDP HFA 80 μg versus 320 μg was 0.260, suggesting approximate
dose proportionality (4-fold difference). Pharmacokinetic results for BDP were similar
to those seen for 17-BMP. All doses of intranasal and orally inhaled BDP HFA were
well tolerated, and no treatment-related adverse events were reported.
Conclusions
The results of this study suggest that 80 and 320 μg BDP HFA nasal aerosols have substantially
lower systemic bioavailability than 320 μg orally inhaled BDP HFA in healthy subjects.
All treatments were well tolerated. ClinicalTrials.gov identifier: NCT01537692.
Key words
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Article info
Publication history
Published online: May 24, 2012
Accepted:
April 24,
2012
Identification
Copyright
© 2012 Elsevier HS Journals, Inc. Published by Elsevier Inc. All rights reserved.
