Evaluation of the buccal component of systemic absorption with inhaled fluticasone propionate

Background-Inhaled corticosteroids have dose related systemic effects deter mined by oral (swallowed or oropharyngeal absorption) and lung bioavailabil ity. A study was undertaken to evaluate the significance of oropharyngeal a bsorption for fluticasone propionate. Methods-Sixteen healthy volunteers of mean age 29.3 years were studied usin g an open randomised, placebo controlled, four way crossover design. Treatm ents were: (a) fluticasone metered dose inhaler (pMDI) 250 mu g, 8 puffs; ( b) fluticasone pMDI 250 mu g, 8 puffs + mouth rinsing/gargling (water); (c) fluticasone pMDI 250 mu g, 8 puffs + mouth rinsing/gargling (charcoal); an d (d) placebo pMDI, 8 puffs + mouth rinsing/gargling (water). Overnight (ON UC) and early morning (EMUC) urinary cortisol/creatinine ratios and 8 am se rum cortisol (SC) levels were measured. Results-Significant (p<0.05) suppression of ONUC, EMUC, and SC occurred wit h 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): fl uticasone (5.6, 95% CI 8.4 to 24.5), fluticasone + water (7.6, 95% CI 6.6 t o 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 number s of subjects with an overnight urinary cortisol of <20 nmol/10 hours were 0 (placebo), 11 (fluticasone), 12 (fluticasone + water), and 13 (fluticason e + charcoal). Conclusions-Oropharyngeal absorption of fluticasone does not significantly contribute to its overall systemic bioactivity as assessed by sensitive mea sures of adrenal suppression. In view of almost complete hepatic first pass inactivation with fluticasone, there is no rationale to employ mouth rinsi ng to reduce its systemic effects although it may be of value for reducing oral candidiasis.