Bioavailability of orally administered micronised fluticasone propionate.
OBJECTIVE
The aim of this study was to determine the absolute oral bioavailability of fluticasone propionate (FP) in healthy volunteers.


METHODS
A 3-period incomplete block crossover design was used. On separate occasions, 21 male volunteers received a single 250 microg intravenous dose of FP (n = 21) and twice daily oral doses of either micronised FP 0.1 mg (n = 9), 1 mg (n = 12), 10 mg (n = 11) or placebo (n = 9) for 4 days.


RESULTS
FP was not measurable in the plasma after twice daily oral administration of a 0.1 mg dose. FP concentrations just above the limit of quantification could be measured in only 5 volunteers, and only at some time points, after administration of FP 1 mg twice daily. At a dose of 10 mg twice daily the absolute oral bioavailability of the drug was <1% when a liquid chromatography-mass spectrometry assay was used to assess plasma concentrations. Only oral doses of FP 10 mg twice daily, 10 times greater than the recommended maximum inhaled dose, produced any detectable change in urinary cortisol excretion.


CONCLUSIONS
The results of this study confirm that oral absorption of FP into the systemic circulation is negligible. The swallowed portion of an inhaled dose of FP is unlikely to increase the systemic exposure to the drug, thus decreasing the likelihood of adverse systemic effects.
Falcoz
C
C
Clinical Pharmacology, Glaxo Wellcome Research and Development, Greenford, Middlesex, England. cf18544@GlaxoWellcome.co.uk
Oliver
R
R
McDowall
J E
JE
Ventresca
P
P
Bye
A
A
Daley-Yates
P T
PT
D000284:Administration, Oral; D000328:Adult; D000730:Androstadienes / Q000097:blood / Q000493:pharmacokinetics*; D018927:Anti-Asthmatic Agents / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D002214:Capsules / Q000008:administration & dosage; D018592:Cross-Over Studies; D004311:Double-Blind Method; D000068298:Fluticasone; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D007785:Lactose / Q000737:chemistry; D008297:Male
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D002214:Capsules; D000068298:Fluticasone; D007785:Lactose; D006854:Hydrocortisone