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Pharmacokinetics of Beclomethasone Dipropionate Delivered by Breath-Actuated Inhaler and Metered-Dose Inhaler in Healthy Subjects.

BACKGROUND
Breath-actuated inhalers (BAIs) eliminate the need for hand-breath coordination required of pressurized metered-dose inhalers (MDIs). This pharmacokinetic study compared systemic exposure following beclomethasone dipropionate delivery through BAI versus MDI.


METHODS
This open-label, three-period crossover, single-dose study randomized healthy subjects aged 18-45 years (N = 72) to 1 of 6 treatment sequences containing beclomethasone dipropionate BAI 160 mcg (40 mcg/inhalation, 4 inhalations), beclomethasone dipropionate BAI 320 mcg (80 mcg/inhalation, 4 inhalations), and beclomethasone dipropionate MDI 320 mcg (80 mcg/inhalation, 4 inhalations). Blood samples were collected predose through 24 hours postdose for determination of plasma concentrations of beclomethasone-17-monopropionate (17-BMP), the active metabolite of beclomethasone dipropionate. The primary pharmacokinetic parameters were area under the plasma drug concentration-time curve (AUC) from time 0 (predose) until the last measurable drug concentration (AUC0-t) and maximum plasma drug concentration (Cmax) for 17-BMP. Safety was assessed by adverse events, vital signs, clinical laboratory tests, and physical examinations.


RESULTS
Plasma concentrations of 17-BMP peaked at a median of 10 minutes after the last inhalation of all study treatments and remained measurable for at least 18 hours in most subjects. Mean elimination half-life was ∼4 hours. The AUC0-t and Cmax for 17-BMP were 11% and 14% higher, respectively, when beclomethasone dipropionate 320 mcg was administered through BAI versus MDI, but the 90% confidence intervals of the geometric least squares mean BAI:MDI ratio for each parameter were fully contained within the bioequivalence boundaries of 0.80-1.25. Plasma concentrations of 17-BMP following beclomethasone dipropionate 160 mcg BAI were approximately half those with 320 mcg through BAI or MDI. All treatments were safe and generally well tolerated.


CONCLUSIONS
Systemic availability of 17-BMP following administration of beclomethasone dipropionate was bioequivalent between BAI and MDI at the 320-mcg dose, and approximately dose proportional at the 160- and 320-mcg doses using the BAI.