Absorption kinetics after inhalation of fluticasone propionate via the Diskhaler, Diskus and metered-dose inhaler in healthy volunteers.
OBJECTIVE
The aim of this analysis was to assess the rate and extent of systemic availability of inhaled fluticasone propionate (FP) from 2 dry powder systems (Diskhaler and Diskus) and a metered-dose inhaler (MDI) by deconvolution analysis.


METHODS
The inhalation devices were evaluated in 3 separate studies with identical protocols. 12 healthy male volunteers were randomised to receive FP given as a 1000 microg inhaled dose and 250 microg by intravenous infusion according to a double-blind double-dummy crossover design. The bioavailability of FP after inhalation represents absorption of the drug from the lungs, since the bioavailability of the swallowed portion of the inhaled dose is negligible.


RESULTS
When corrected for the bioavailability (of FP) achieved by each inhalation device, the rate of absorption of FP over the first 2 hours was rapid from all devices. The mean time for absorption of 50% of the bioavailable dose was 1.6, 2.4, and 2.2 hours for the Diskhaler, Diskus and MDI, respectively. Thereafter, absorption from each device was prolonged, with approximately 10% of the dose remaining in the lungs 12 hours after inhalation.


CONCLUSIONS
Irrespective of the inhalation device used, the prolonged absorption of FP into the systemic circulation indicates a long residence time in the lungs.
Brindley
C
C
Drug Metabolism and Pharmacokinetics, Quintiles Scotland Limited, Edinburgh.
Falcoz
C
C
Mackie
A E
AE
Bye
A
A
D000042:Absorption; D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000730:Androstadienes / Q000097:blood / Q000493:pharmacokinetics*; D018927:Anti-Asthmatic Agents / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D000068298:Fluticasone; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D009330:Nebulizers and Vaporizers
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D000068298:Fluticasone