Evaluation of the buccal component of systemic absorption with inhaled fluticasone propionate.
BACKGROUND
Inhaled corticosteroids have dose related systemic effects determined by oral (swallowed or oropharyngeal absorption) and lung bioavailability. A study was undertaken to evaluate the significance of oropharyngeal absorption for fluticasone propionate.


METHODS
Sixteen healthy volunteers of mean age 29.3 years were studied using an open randomised, placebo controlled, four way crossover design. Treatments were: (a) fluticasone metered dose inhaler (pMDI) 250 microg, 8 puffs; (b) fluticasone pMDI 250 microg, 8 puffs + mouth rinsing/gargling (water); (c) fluticasone pMDI 250 microg, 8 puffs + mouth rinsing/gargling (charcoal); and (d) placebo pMDI, 8 puffs + mouth rinsing/gargling (water). Overnight (ONUC) and early morning (EMUC) urinary cortisol/creatinine ratios and 8 am serum cortisol (SC) levels were measured.


RESULTS
Significant (p<0. 05) suppression of ONUC, EMUC, and SC occurred with each active treatment compared with placebo. The mean values (95% CI for difference from placebo) were: (a) ONUC (nmol/mmol): fluticasone (2. 8, 95% CI 3.6 to 7.9), fluticasone + water (3.1, 95% CI 3.3 to 7.7), fluticasone + charcoal (2.3, 95% CI 4.1 to 8.5); placebo (8.6); (b) EMUC (nmol/mmol): fluticasone (5.6, 95% CI 8.4 to 24.5), fluticasone + water (7.6, 95% CI 6.6 to 22.4); fluticasone + charcoal (5.6, 95% CI 8.7 to 24.5); placebo (22.1). There were no significant differences between active treatments. The numbers of subjects with an overnight urinary cortisol of <20 nmol/10 hours were 0 (placebo), 11 (fluticasone), 12 (fluticasone + water), and 13 (fluticasone + charcoal).


CONCLUSIONS
Oropharyngeal absorption of fluticasone does not significantly contribute to its overall systemic bioactivity as assessed by sensitive measures of adrenal suppression. In view of almost complete hepatic first pass inactivation with fluticasone, there is no rationale to employ mouth rinsing to reduce its systemic effects although it may be of value for reducing oral candidiasis.
Dempsey
O J
OJ
Department of Clinical Pharmacology & Therapeutics, Ninewells Hospital & Medical School, University of Dundee, Dundee DD1 9SY, UK.
Coutie
W J
WJ
Wilson
A M
AM
Williams
P
P
Lipworth
B J
BJ
D000042:Absorption; D000280:Administration, Inhalation; D000287:Administration, Topical; D000311:Adrenal Glands / Q000187:drug effects; D000328:Adult; D000704:Analysis of Variance; D000730:Androstadienes / Q000493:pharmacokinetics*; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D002606:Charcoal; D016001:Confidence Intervals; D003404:Creatinine / Q000652:urine; D018592:Cross-Over Studies; D003864:Depression, Chemical; D016503:Drug Delivery Systems; D005260:Female; D000068298:Fluticasone; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D008297:Male; D009061:Mouth Mucosa / Q000378:metabolism*; D009330:Nebulizers and Vaporizers; D014867:Water
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D014867:Water; D002606:Charcoal; D003404:Creatinine; D000068298:Fluticasone; D006854:Hydrocortisone