Pharmacokinetics of flunisolide administered via metered dose inhaler withand without a spacer device and following oral administration

Background: After inhalation of a glucocorticoid from a meter dose inhaler (MDI), a certain portion of the delivered dose is deposited in the lungs, a nd the remainder is deposited in the oropharynx. Objective: To examine the absolute bioavailability of flunisolide given ora lly via metered dose inhaler, and metered dose inhaler with a commercially available spacer device as well as to determine the fraction of drug deposi ted in the lungs following inhalation. Methods: Twenty-four healthy volunteers were enrolled in the study; twenty- two completed the study. The IRE approved the study protocol, and informed consent was obtained. Volunteers received four treatments: treatment A (MDI ), 1.0 mg inhaled flunisolide; treatment B (MDI-S), 1.0 mg inhaled flunisol ide with a spacer device; treatment C, 1.0 mg of orally administered flunis olide with 240 mt of water; and treatment D, 1.0 mg intravenous flunisolide by IV push in the antecubital vein over 60 seconds. Plasma and urine fluni solide were quantified by HPLC/mass spectrometry/mass spectrometry. Results: Flunisolide is a corticosteroid with low oral bioavailability (6.7 %), which was found to be lower than previously reported. Similar AUCs were observed between the MDI and MDI-S groups, but by using mass balance equat ions, it appears that more flunisolide was delivered to the lungs in the MD I-S group (410 mu g versus 280 mu g). Oropharyngeal deposition was an impor tant difference between the two inhaler groups. Approximately an Ii-fold re duction in the oropharyngeal deposition of flunisolide through use of the s pacer device was observed. Conclusions: Use of a spacer device improved pulmonary delivery of flunisol ide by almost 50% and significantly decreased the oropharyngeal exposure to drug.