Pharmacokinetics of flunisolide administered via metered dose inhaler with and 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, and the remainder is deposited in the oropharynx.


OBJECTIVE
To examine the absolute bioavailability of flunisolide given orally via metered dose inhaler, and metered dose inhaler with a commercially available spacer device as well as to determine the fraction of drug deposited in the lungs following inhalation.


METHODS
Twenty-four healthy volunteers were enrolled in the study; twenty-two completed the study. The IRB 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 flunisolide with a spacer device; treatment C, 1.0 mg of orally administered flunisolide with 240 mL of water; and treatment D, 1.0 mg intravenous flunisolide by IV push in the antecubital vein over 60 seconds. Plasma and urine flunisolide 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 equations, it appears that more flunisolide was delivered to the lungs in the MDI-S group (410 microg versus 280 microg). Oropharyngeal deposition was an important difference between the two inhaler groups. Approximately an 11-fold reduction in the oropharyngeal deposition of flunisolide through use of the spacer device was observed.


CONCLUSIONS
Use of a spacer device improved pulmonary delivery of flunisolide by almost 50% and significantly decreased the oropharyngeal exposure to drug.
Dickens
G R
GR
Division of Pharmacy Practice and Science, University of Kentucky Medical Center, Lexington 40536-0084, USA.
Wermeling
D P
DP
Matheny
C J
CJ
John
W
W
Abramowitz
W
W
Sista
S M
SM
Foster
T
T
Choudhury
S
S
D000284:Administration, Oral; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D005446:Fluocinolone Acetonide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009330:Nebulizers and Vaporizers
D018927:Anti-Asthmatic Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005446:Fluocinolone Acetonide; C007734:flunisolide