Systemic exposure to fluticasone propionate administered via metered-dose inhaler containing chlorofluorocarbon or hydrofluoroalkane propellant.
OBJECTIVE
The pharmacokinetic profile of a single dose of inhaled fluticasone propionate (FP) administered via a metered-dose inhaler (MDI), containing either a chlorofluorocarbon (CFC) or hydrofluoroalkane (HFA) propellant was investigated in healthy volunteers.


METHODS
Two randomised, double-blind, crossover studies were conducted, each in 12 male volunteers. Both studies compared pharmacokinetic data after a single inhaled dose of FP 1000 microg from a MDI containing either CFC (CFC MDI) or HFA (HFA MDI) with a single intravenous dose of FP 250 microg.


RESULTS
The maximum plasma FP concentrations after inhalation via the 2 types of MDI were almost identical (0.56 and 0.54 microg/L for CFC MDI and HFA MDI, respectively); bioavailability values of inhaled FP from the 2 MDIs were also similar (geometric mean values: 26.4% via the CFC MDI and 28.6% via the HFA MDI). Inhalation of FP via both MDI formulations produced similar reductions in urinary cortisol excretion over 12 and 24 hours postdose.


CONCLUSIONS
The bioavailability values of FP after inhalation via a CFC MDI and an HFA MDI are similar. The 2 formulations deliver comparable amounts of FP, and systemic exposures to FP from the 2 devices, measured by urinary cortisol excretion, are not significantly different.
Mackie
A E
AE
Lilly Research Centre, Windlesham, Surrey, England.
McDowall
J E
JE
Ventresca
P
P
Bye
A
A
Falcoz
C
C
Daley-Yates
P T
PT
D000280:Administration, Inhalation; D000328:Adult; D000335:Aerosol Propellants / Q000008:administration & dosage / Q000737:chemistry; D000730:Androstadienes / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D018927:Anti-Asthmatic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D017402:Chlorofluorocarbons / Q000008:administration & dosage / Q000737:chemistry*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D000068298:Fluticasone; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage / Q000737:chemistry*; D006854:Hydrocortisone / Q000652:urine; D007262:Infusions, Intravenous; D008297:Male; D009330:Nebulizers and Vaporizers; D005466:Fluorocarbons
D000335:Aerosol Propellants; D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D017402:Chlorofluorocarbons; D000068298:Fluticasone; D006845:Hydrocarbons, Fluorinated; D006854:Hydrocortisone; C094049:apaflurane; D005466:Fluorocarbons